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Gd
Terms modified by Gd Selected AbstractsEffects of in utero exposure to 2,2,,4,4,,5,5,-hexachlorobiphenyl (PCB 153) on somatic growth and endocrine status in rat offspringCONGENITAL ANOMALIES, Issue 4 2008Kenichi Kobayashi ABSTRACT Exposure to polychlorobiphenyl (PCB) mixtures at an early stage of development has been reported to affect endocrine glands; however, little is known about the precise toxicological properties of individual PCB. The present study was undertaken to determine whether prenatal exposure to 2,2,,4,4,,5,5,-hexachlorobiphenyl (PCB 153), a di- ortho -substituted non-coplanar congener, affects postnatal development in rat offspring. Pregnant Sprague-Dawley rats (Crj: CD (SD) IGS) were given PCB 153 (0, 16, or 64 mg/kg/day) orally from gestational day (GD) 10 through GD 16, and developmental parameters in the male and female offspring were examined. We found no dose-dependent changes in body weight, body length (nose,anus length), tail length, or the weights of kidneys, testes, ovaries and uterus in offspring at 1 or 3 weeks of age. Liver weights were increased in the PCB 153,treated groups, although we observed a significant difference only in males. Anogenital distance was unaffected in the PCB 153,treated groups. We observed a significant dose-dependent decrease in the plasma concentrations of thyroxine and tri-iodothyronine, whereas those of thyroid-stimulating hormone were not significantly changed. In addition, there were no dose-dependent changes in plasma concentrations of growth hormone and insulin-like growth factor-I in any dose group. These findings suggest that prenatal exposure to PCB 153 (GD 10,16, 16,64 mg/kg/day) may alter the thyroid status in rat offspring to some extent without affecting somatic growth or its related hormonal parameters. [source] Morphological and immunohistochemical studies on cleft palates induced by 2,3,7,8-tetrachlorodibenzo- p -dioxin in miceCONGENITAL ANOMALIES, Issue 2 2008Kumiko Fujiwara ABSTRACT Morphological and immunohistological examinations were performed to reveal the mechanisms of cleft palate induction by 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD). ICR strain mice 8,10 weeks of age were used in the study. TCDD was administered in olive oil on gestation day (GD) 12.5 with gastric tubes at 40 ,g/kg. From GD 13.5 to 16.5, palates were examined by scanning electron microscopy (SEM), hematoxyline,eosin (HE) staining, and immunohistochemical staining of FGFR1/2, TGF-,3, MSX1 and LHX8. In the control group, both of the palatal shelves began elevating on GD 14.0 and finished within 6 h. After the elevation, all of the shelves had completely fused with each other on GD 14.5. In the TCDD-treated group, palatal shelves elevated 1 day later than in the control group. However, all palates had elevated by GD 15.0. After the elevation, the shelves contacted each other and fused; however, they were separated on GD16.0. HE staining showed that medial edge epithelium (MEE) was thinner in the TCDD group than in the control group. MEE observed under a high magnification (×2500) exhibited filopodia-like filaments and the cells were bulged in the control group. In contrast, in the TCDD group, no filaments were observed and the cells were flat with unclear boundaries. Immunohistologically, there were no characteristic findings except for FGFR1. FGFR1 was not expressed in the TCDD group after the fusion phase (GD 14.5). TCDD induces many morphological and molecular changes to MEE cells and causes cleft palates. [source] Prenatal developmental toxicity studies of 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (p, p,-DDT) in rats and rabbitsCONGENITAL ANOMALIES, Issue 4 2001Ken L. Takahashi ABSTRACT, The studies were conducted in rats and rabbits to elucidate the potential developmental toxicity of p, p'-DDT in general accordance with the improved Japanese MAFF guidelines (12-Nousan-No. 8147,2,1,18, 2000). p, p'-DDT suspended in 1% aqueous solution of CMC was administered orally to pregnant Jcl:SD rats on gestational days (GD) 6,19 at a dose of 0,5, 25, or 100 mg/kg/day and to pregnant KbI: JW rabbits on GD 6,27 at a dose of 0,5,20, or 80 mg/kg/day. Maternal animals were killed on the day after the last day of administration for morphological examination of their fetuses with special attention to the reproductive organs. Adverse effects on maternal animals were found only at the highest dose in both species; i.e., clonic convulsion (2/24 in rats, 5/22 in rabbits), mortality (1/24 in rats), abortion or premature delivery (4/22 in rabbits), and reduced body weight gains and food consumption. However, the control and treated groups showed comparable values for the numbers of corpora lutea and implants, percent preimplantation losses, number of live fetuses, percent resorptions and fetal deaths, sex ratio, fetal body weights, and placental weights in both species, and anogenital distance and testicular histology in rats. Although fetal examination revealed slightly increased incidence of 27 presacral vertebrae in the highest dose group in rats, there was no treatment-related increase in the incidence of malformations in any of the species. Based on these results, it is concluded that p, p'-DDT causes no malformations, including male reproductive organ abnormalities, in either rats or rabbits, although it results in an increased incidence of skeletal variations in rats at a maternally toxic dose. [source] Misregulation of gene expression in the redox-sensitive NF-,b-dependent limb outgrowth pathway by thalidomideDEVELOPMENTAL DYNAMICS, Issue 2 2002Jason M. Hansen Abstract Thalidomide is known to induce oxidative stress, but mechanisms have not been described through which oxidative stress could contribute to thalidomide-induced terata. Oxidative stress modulates intracellular glutathione (GSH) and redox status and can perturb redox-sensitive processes, such as transcription factor activation and/or binding. Nuclear factor-kappa B (NF-,B), a redox-sensitive transcription factor involved in limb outgrowth, may be modulated by thalidomide-induced redox shifts. Thalidomide-resistant Sprague-Dawley rat embryos (gestation day [GD] 13) treated with thalidomide in utero showed no changes in GSH distribution in the limb but thalidomide-sensitive New Zealand White rabbit embryos (GD 12) showed selective GSH depletion in the limb bud progress zone (PZ). NF-,B and regulatory genes that initiate and maintain limb outgrowth and development, such as Twist and Fgf-10, are selectively expressed in the PZ. Green fluorescent protein (GFP) reporter vectors containing NF-,B binding promoter sites were transfected into both rat and rabbit limb bud cells (LBCs). Treatment with thalidomide caused a preferential decrease in GFP expression in rabbit LBCs but not in rat LBCs. N-acetylcysteine and ,-N-t-phenylbutyl nitrone (PBN), a free radical trapping agent, rescued GFP expression in thalidomide-treated cultures compared with cultures that received thalidomide only. In situ hybridization showed a preferential decrease in Twist, Fgf-8, and Fgf-10 expression after thalidomide treatment (400 mg/kg per day) in rabbit embryos. Expression in rat embryos was not affected. Intravenous cotreatment with PBN and thalidomide (gavage) in rabbits restored normal patterns and localization of Twist, Fgf-8, and Fgf-10 expression. These findings show that NF-,B binding is diminished due to selective thalidomide-induced redox changes in the rabbit, resulting in the significant attenuation of expression of genes necessary for limb outgrowth. © 2002 Wiley-Liss, Inc. [source] The hinge region operates as a stability switch in cGMP-dependent protein kinase I,FEBS JOURNAL, Issue 9 2007Arjen Scholten The molecular mechanism of cGMP-dependent protein kinase activation by its allosteric regulator cyclic-3,,5,-guanosine monophosphate (cGMP) has been intensely studied. However, the structural as well as thermodynamic changes upon binding of cGMP to type I cGMP-dependent protein kinase are not fully understood. Here we report a cGMP-induced shift of Gibbs free enthalpy (,,GD) of 2.5 kJ·mol,1 as determined from changes in tryptophan fluorescence using urea-induced unfolding for bovine PKG I,. However, this apparent increase in overall stability specifically excluded the N-terminal region of the kinase. Analyses of tryptic cleavage patterns using liquid chromatography-coupled ESI-TOF mass spectrometry and SDS/PAGE revealed that cGMP binding destabilizes the N-terminus at the hinge region, centered around residue 77, while the C-terminus was protected from degradation. Furthermore, two recombinantly expressed mutants: the deletion fragment ,1-77 and the trypsin resistant mutant Arg77Leu (R77L) revealed that the labile nature of the N-terminus is primarily associated with the hinge region. The R77L mutation not only stabilized the N-terminus but extended a stabilizing effect on the remaining domains of the enzyme as well. These findings support the concept that the hinge region of PKG acts as a stability switch. [source] A numerical comparison of 2D resistivity imaging with 10 electrode arraysGEOPHYSICAL PROSPECTING, Issue 5 2004Torleif Dahlin ABSTRACT Numerical simulations are used to compare the resolution and efficiency of 2D resistivity imaging surveys for 10 electrode arrays. The arrays analysed include pole-pole (PP), pole-dipole (PD), half-Wenner (HW), Wenner-, (WN), Schlumberger (SC), dipole-dipole (DD), Wenner-, (WB), ,-array (GM), multiple or moving gradient array (GD) and midpoint-potential-referred measurement (MPR) arrays. Five synthetic geological models, simulating a buried channel, a narrow conductive dike, a narrow resistive dike, dipping blocks and covered waste ponds, were used to examine the surveying efficiency (anomaly effects, signal-to-noise ratios) and the imaging capabilities of these arrays. The responses to variations in the data density and noise sensitivities of these electrode configurations were also investigated using robust (L1 -norm) inversion and smoothness-constrained least-squares (L2 -norm) inversion for the five synthetic models. The results show the following. (i) GM and WN are less contaminated by noise than the other electrode arrays. (ii) The relative anomaly effects for the different arrays vary with the geological models. However, the relatively high anomaly effects of PP, GM and WB surveys do not always give a high-resolution image. PD, DD and GD can yield better resolution images than GM, PP, WN and WB, although they are more susceptible to noise contamination. SC is also a strong candidate but is expected to give more edge effects. (iii) The imaging quality of these arrays is relatively robust with respect to reductions in the data density of a multi-electrode layout within the tested ranges. (iv) The robust inversion generally gives better imaging results than the L2 -norm inversion, especially with noisy data, except for the dipping block structure presented here. (v) GD and MPR are well suited to multichannel surveying and GD may produce images that are comparable to those obtained with DD and PD. Accordingly, the GD, PD, DD and SC arrays are strongly recommended for 2D resistivity imaging, where the final choice will be determined by the expected geology, the purpose of the survey and logistical considerations. [source] Gaucher disease: mutation and polymorphism spectrum in the glucocerebrosidase gene (GBA),,HUMAN MUTATION, Issue 5 2008Kathleen S. Hruska Abstract Gaucher disease (GD) is an autosomal recessive disorder caused by the deficiency of glucocerebrosidase, a lysosomal enzyme that catalyses the hydrolysis of the glycolipid glucocerebroside to ceramide and glucose. Lysosomal storage of the substrate in cells of the reticuloendothelial system leads to multisystemic manifestations, including involvement of the liver, spleen, bone marrow, lungs, and nervous system. Patients with GD have highly variable presentations and symptoms that, in many cases, do not correlate well with specific genotypes. Almost 300 unique mutations have been reported in the glucocerebrosidase gene (GBA), with a distribution that spans the gene. These include 203 missense mutations, 18 nonsense mutations, 36 small insertions or deletions that lead to either frameshifts or in-frame alterations, 14 splice junction mutations, and 13 complex alleles carrying two or more mutations in cis. Recombination events with a highly homologous pseudogene downstream of the GBA locus also have been identified, resulting from gene conversion, fusion, or duplication. In this review we discuss the spectrum of GBA mutations and their distribution in the patient population, evolutionary conservation, clinical presentations, and how they may affect the structure and function of glucocerebrosidase. Hum Mutat 29(5), 567,583, 2008. Published 2008 Wiley-Liss, Inc. [source] Analysis of the glucocerebrosidase gene and mutation profile in 144 Italian gaucher patients,,HUMAN MUTATION, Issue 3 2002Mirella Filocamo Abstract Gaucher disease (GD), the most prevalent lysosomal storage disease characterized by a remarkable degree of clinical variability, results from deleterious mutations in the glucocerebrosidase gene (GBA). In this paper we report the molecular characterization of 144 unrelated Italian GD patients with the three types of the disease. The allelic frequencies of Italians are reported and the mutation profile is analyzed. Besides the common N370S, L444P, RecNciI, G202R, IVS2+1G>A, D409H, F213I mutations, the different molecular strategies, used for the mutation detection, identified the rare N107L, R131C, R170C, R170P, N188S, S196P, R285C, R285H, W312C, D399N, A446P, IVS10-1G>A, Rec,55, total gene deletion, as well as 12 mutant alleles that were exclusively present in the Italian population until now: the previously reported R353G, N370S+S488P mosaicism, IVS8(-11delC)-14T>A), Rec I, Y418C, and the seven novel alleles D127X, P159T, V214X, T231R, L354X, H451R, and G202R+M361I. The wide phenotypic differences observed within the genotypic groups as well as between siblings implicate a significant contribution of other modifying genetic and/or non-genetic factors and claim a comprehensive valuation of the patient including clinical., biochemical and molecular investigations for prognosis, appropriate interventive therapy and reliable genetic counseling. © 2002 Wiley-Liss, Inc. [source] Weather regimes and sea surge variations over the Gulf of Lions (French Mediterranean coast) during the 20th centuryINTERNATIONAL JOURNAL OF CLIMATOLOGY, Issue 2 2008A. Ullmann Abstract Hourly sea surge variations observed at three tide-gauge stations (Grau-de-la-Dent(GD) located in the Rhône Delta, Sète(SE), and Port-Vendres(PV)) around the Gulf of Lions are strongly correlated during the wintertime period (October to March) of 1986-1995. Relationships between the early morning (6 a.m. UTC) sea surge observed at Grau-de-la-Dent station and five weather regimes,Zonal (ZO), East-Atlantic (EA), Greenland Above (GA), Blocking (BL), and Atlantic Ridge (AR),over the northeast Atlantic and Europe (40°W,40°E, 30 ,70°N) are analysed during the wintertime period of 1905-2002. More than 75% of sea surges , 40 cm occur during both of the weather regimes associated with a negative North Atlantic Oscillation(NAO) phase (41.2 and 34% during BL and GA weather regimes, respectively), ahead of low pressure travelling usually southeastward, on a stormtrack shifted south of 55°N. The relationships between monthly/seasonal frequency of weather regime and 75th percentile of sea surge at GD tend to strengthen during the 20th century: for example, correlation between seasonal frequencies of GA and 75th percentile of sea surge increases from 0.07 (not significant) in 1905,40 to 0.83 (signifiicant at the one-sided 99% level) in 1974,2002. Copyright © 2007 Royal Meteorological Society [source] Lack of association between pro-inflammatory cytokine (IL-6, IL-8 and TNF-,) gene polymorphisms and Graves' diseaseINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 6 2005R.-H. Chen Summary Graves' disease (GD) is a common, autoimmune disease involving the thyroid gland, and it has been previously suggested that pro-inflammatory cytokines are involved in the disease's pathogenesis. The aim of this study was to test whether the interleukin (IL)-6 gene promoter region, or tumour necrosis factor (TNF)-, or IL-8 gene 3,-untranslated region (3,-UTR) polymorphisms could provide useful genetic markers for an individual's susceptibility to GD. A normal control group of 60 healthy people and 95 patients featuring GD were examined. Polymerase chain reaction (PCR)-based restriction analysis was performed for the three gene polymorphisms using endonucleases BsrBI, NcoI and ApaLI, respectively. We found no significant difference between the frequencies of genotype and allelic variants for the IL-6 gene promoter (,572 G/C), the TNF-, gene promoter (,308 A/G) and the IL-8 gene 3,-UTR (2767 A/G) for GD patients and for normal controls. Cytokines are a large group of proteins that may elicit multiple effects upon immunological reactions. It still appears to be very worthwhile to continue to aggressively search for cytokine gene polymorphisms in order to predict the development of such disease. [source] Effects of screw configurations on the grafting of maleic anhydride grafted low-density polyethylene in reactive extrusionJOURNAL OF APPLIED POLYMER SCIENCE, Issue 6 2008Hui Fang Abstract The effects of screw configurations, that is, the staggering angles and disc widths of the kneading blocks, on grafting reactive extrusion for maleic anhydride grafted low-density polyethylene were investigated in a corotating twin-screw extruder. Samples were collected from three positions along the screw and the die exit. The grafting degree (GD) of the specimens was evaluated by titration. It was found that the kneading block configurations had a significant influence on the grafting reactive extrusion. In addition, another three groups of extrusion experiments were performed to explore the intrinsic relationship between the GD, the degree of fill in the screw channel, the residence time distribution (RTD), and the mixing intensity in various screw configurations. The experimental results indicated that the location of the melting endpoint significantly affected the position at which the reaction began; the degree of fill, RTD, and mixing performance of the screw played important roles in the grafting reaction. The reverse kneading blocks with a narrow disc width, which had a high degree of fill and good mixing capacity, enhanced the increase in GD along the screw during the reactive extrusion. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008 [source] Neurobehavioral toxicity study of dibutyl phthalate on rats following in utero and lactational exposureJOURNAL OF APPLIED TOXICOLOGY, Issue 7 2009Yuanfeng Li Abstract To investigate the neurobehavioral effects of dibutyl phthalate (DBP), an important endocrine disruptor known for reproductive toxicity, on rodent offspring following in utero and lactational exposure, pregnant Wistar rats were treated with DBP (0, 0.037, 0.111, 0.333 and 1% in the diet) from gestation day (GD) 6 to postnatal day (PND) 28, and selected developmental and neurobehavioral parameters of the offspring were measured. There were no significant effects of DBP on body weight gain of the dams during GD 6,20 or on the pups' ages of pinna detachment, incisor eruption or eye opening. Exposure to 1% DBP prolonged gestation period, decreased body weight in both male and female pups, depressed surface righting (PND 7) in male pups, shortened forepaw grip time (PND 10), enhanced spatial learning and reference memory (PND 35) in male pups. Exposure to 0.037% DBP also shortened forepaw grip time (PND 10), but inhibited spatial learning and reference memory in male pups. Sex × treatment effects were found in forepaw grip time (PND 10), spatial learning and reference memory, and the male pups appeared to be more susceptible than the females. However, all levels of DBP exposure did not significantly alter surface righting (PND 4), air righting (PND 16), negative geotaxis (PND 4 or 7), cliff avoidance (PND 7) or open field behavior (PND 28) in either sex. Overall, the dose level of DBP in the present study produced a few adverse effects on the neurobehavioral parameters, and it may alter cognitive abilities of the male rodent. Copyright © 2009 John Wiley & Sons, Ltd. [source] Differential developmental toxicities of di- n -hexyl phthalate and dicyclohexyl phthalate administered orally to ratsJOURNAL OF APPLIED TOXICOLOGY, Issue 6 2009Anne-Marie Saillenfait Abstract The objective of this study was to evaluate the developmental toxic potential of di- n -hexyl phthalate (DnHP) and dicyclohexyl phthalate (DCHP) in rats. Pregnant Sprague,Dawley rats were exposed to DnHP or DCHP at doses of 0 (olive oil), 250, 500 and 750 mg kg,1 per day, by gavage, on gestational days (GD) 6,20. Maternal food consumption and body weight gain were significantly reduced at 750 mg kg,1 per day of DnHP and at the two high doses of DCHP. Slight changes in liver weight associated with peroxisomal enzyme induction were seen in dams treated with DnHP or DCHP. DnHP caused dose-related developmental toxic effects, including marked embryo mortality at 750 mg kg,1 per day, and presence of malformations (mainly cleft palate, eye defects and axial skeleton abnormalities) and significant decreases in fetal weight at 500 and 750 mg kg,1 per day. Significant delay of ossification and increase in the incidence of skeletal variants (e.g. supernumerary lumbar ribs) also appeared at 250 mg kg,1 per day. DCHP produced fetal growth retardation at 750 mg kg,1 per day, as evidenced by significant reduction of fetal weight. DnHP and DCHP induced a significant and dose-related decrease in the anogenital distance of male fetuses at all doses, and there was a significant increase in the incidence of male fetuses with undescended testis at 500 and 750 mg kg,1 per day of DnHP. In conclusion, DnHP showed clear embryolethality and teratogenicity, but not DCHP. There was evidence that both phthalates could alter the development of the male reproductive system after in utero exposure, DnHP being much more potent than DCHP. Copyright © 2009 John Wiley & Sons, Ltd. [source] Effect of octanol:water partition coefficients of organophosphorus compounds on biodistribution and percutaneous toxicity,,JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 5 2006Steven E. Czerwinski Abstract Knowledge of partition coefficient (log P) data can play a critical role in understanding the pharmacokinetic and pharmacodistributive properties of toxic organophosphorus (OP) compounds. Using a recently published gas chromatographic method, the octanol:water log P values for the compounds tabun (GA), sarin (GB), cyclosarin (GF), and O -ethyl- S -(2-diisopropylaminoethyl) methylphosphonothiolate (VX) were determined to be 0.384 ± 0.033, 0.299 ± 0.016, 1.038 ± 0.055, and 0.675 ± 0.070, respectively. Based on these data, the log P value of the fluorophosphonate fragment, common to GB, soman (GD), and GF, was determined to be ,2.256 ± 0.273. The predictive value for absorption and distribution of the determined log P values was compared to measured values. The time to onset of local fasciculations (47.3, 29.0, 8.8, 8.5, and 6.3 min, respectively) in guinea pigs exposed percutaneously to equilethal doses of GA, VX, GF, GB, or GD was used as an indicator of dermal penetration. There was a good correlation (r = 0.95) between the measured log P value and the rate of onset of local fasciculations. Assuming a direct correspondence, equilibrium tissue:blood log P may be estimated from octanol:water log P. Comparison of the estimated and directly measured tissue:blood log P revealed a correlation of 0.8 for GD in liver, muscle, and adipose tissue. Our results demonstrate the use of log P data to both predict absorption and determine the distribution of OP compounds in tissues. This facilitates further estimates of in vivo OP effects from in vitro experiments. © 2006 Wiley Periodicals, Inc. J Biochem Mol Toxicol 20:241,246, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20140 [source] Spatial and Temporal Ontogenies of Glutathione Peroxidase and Glutathione Disulfide Reductase During Development of the Prenatal RatJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 4 2001Hyungsuk Choe Abstract Spatial and temporal expression and regulation of the antioxidant enzymes, glutathione peroxidase (GSH-Px), glutathione disulfide reductase (GSSG-Rd) may be important in determining cell-specific susceptibility to embryotoxicants. Creation of tissue-specific ontogenies for antioxidant enzyme activities during development is an important first step in understanding regulatory relationships. Early organogenesis-stage embryos were grouped according to the somite number (GD 9,13), and fetuses were evaluated by gestational day (GD 14,21). GSH-Px activities in the visceral yolk sac (VYS) increased on consecutive days from GD 9 to GD 13, representing a 5.7-fold increase during this period of development. GSH-Px activities in VYS decreased after GD 13, ultimately constituting a 37% decrease at GD 21. Head, heart, and trunk specific activities generally increased from GD 9 to GD 13 albeit not to the same magnitude as detected in the VYS. GSSG-Rd activities showed substantial increases in the VYS from GD 9 to GD 13, 6.3-fold and decreased thereafter to 50% by GD 21. The greatest changes in enzyme activities were noted in the period between GD 10 and GD 11, where the embryo establishes an active cardiovascular system and begins to convert to aerobic metabolism. Generally, from GD 14,21, embryonic organ GSH-Px and GSSG-Rd activities either remained constant or increased as gestation progressed. These studies suggest the importance of the VYS in dealing with ROS and protecting the embryo. Furthermore, understanding the consequences of lower antioxidant activities during organogenesis may help to pinpoint periods of teratogenic susceptibility to xenobiotics and increased oxygen. © 2001 John Wiley & Sons, Inc. J Biochem Mol Toxicol 15:197,206, 2001 [source] Application of crosslinkers to dentin collagen enhances the ultimate tensile strengthJOURNAL OF BIOMEDICAL MATERIALS RESEARCH, Issue 1 2007Ana Karina B. Bedran-Russo Abstract The stabilization of dentin collagen with biocompatible crosslinking agents may be of clinical importance to improve dentin bond strength. The present study aimed to evaluate the effect of three collagen crosslinking agents on the ultimate tensile strength (UTS) of undemineralized and demineralized dentin. Ten freshly extracted sound molars were sectioned into 0.5 × 0.5 mm2 thick beams. The beams were either demineralized or kept undemineralized. Then, specimens were subdivided into four groups according to treatments,PBS solution (control), 5% glutaraldehyde (GD), 0.5% proanthocyanidin PBS solution (PA), and 0.625% genipin PBS solution (GE). Specimens were kept in their respective solutions for either 4 or 40 h. To assess UTS, specimens were subjected to tensile forces at a crosshead speed of 1 mm/min. Statistical analysis was performed using two-way ANOVA and Fisher's PLSD test (p < 0.05). Statistically significant increases in UTS were observed for demineralized dentin after PA and GE dentin treatment, when compared with those of the control group. Dentin treated with GD showed no statistically significant differences in UTS when compared with that the control. Undemineralized dentin revealed no significant differences as compared to that of the control, regardless of the collagen crosslinkers. The application of two naturally occurring crosslinkers, i.e., PA and GE, to dentin collagen significantly improves UTS, indicating its potential value in restorative dentistry. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2007 [source] Association between the TAP2 gene codon 665 polymorphism and Graves' DiseaseJOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 3 2006Rong-Hsing Chen Abstract A total of 95 patients with active Graves' disease (GD) and 105 normal healthy subjects were enrolled in this study, which attempted to determine whether single-site polymorphisms of the transporter associated with antigen processing 2 (TAP2) gene contribute to an individual's susceptibility to GD. Such polymorphisms were detected using polymerase chain reaction (PCR)-based restriction analysis. Associations between GD and the three site polymorphisms of the TAP2 gene at codons 379, 565, and 665 were investigated. The results of the genotype analysis revealed that the frequency of the GG homozygote's presence at codon 665 was lower, and that of the AA homozygote's presence was greater in GD patients (15.8% and 36.8%, respectively) compared to normal controls (34.3% and 16.2%, respectively; P<0.001). The OR (OD) for the risk of occurrence for the AA homozygote and AG heterozygote compared to the GG homozygote (as was the case for the GD patients) was respectively 4.941 and 2.117, with respective 95% confidence intervals (CI) of 2.303,10.598 and 1.020,4.369. The allelic analysis also demonstrated reduced G and enhanced A allele frequencies for GD patients compared to controls (respectively 39.5% vs. 59.0% [G allele], and 60.5% vs. 41.0% [A allele]; P=0.0001; OR=2.219, 95% CI: 1.449,3.395). By contrast, the differences between patient and control groups for the frequency of appearance of genotypes and allelic variants at codon 379 (P=0.522 and P=0.306, respectively) and codon 565 (P=0.199 and P=0.157, respectively) did not appear to be significant. These data reveal that the single-site polymorphism of the TAP2 gene at codon 665 may be an indicator for predicting GD development. J. Clin. Lab. Anal. 20:93,97, 2006. © 2006 Wiley-Liss, Inc. [source] Effect of systemic parathyroid hormone (1,34) and a , -tricalcium phosphate biomaterial on local bone formation in a critical-size rat calvarial defect modelJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 5 2010Jonathan I. Yun Yun JI, Wikesjö UME, Borke JL, Bisch FC, Lewis JE, Herold RW, Swiec GD, Wood JC, McPherson III JC. Effect of systemic parathyroid hormone (1,34) and a ,-tricalcium phosphate biomaterial on local bone formation in a critical-size rat calvarial defect model. J Clin Periodontol 2010; 37: 419,426 doi: 10.1111/j.1600-051X.2010.01547.x Abstract Objective: The objective of this study was to evaluate local bone formation following systemic administration of parathyroid hormone (1,34) (PTH), a surgically implanted synthetic , -tricalcium phosphate (, -TCP) bone biomaterial serving as a matrix to support new bone formation. Materials and Methods: Critical-size, 8 mm, calvarial through-and-through osteotomy defects were surgically created in 100 adult male Sprague,Dawley rats. The animals were randomized into five groups of 20 animals each to receive one of the following treatments: PTH (15 ,g PTH/kg/day; subcutaneously), PTH/, -TCP, , -TCP, or particulate human demineralized freeze-dried bone (DFDB), and sham-surgery controls. Ten animals/group were euthanized at 4 and 8 weeks post-surgery for radiographic and histometric analysis. Results: The histometric analysis showed that systemic PTH significantly enhanced local bone formation, bone fill averaging (±SE) 32.2±4.0% compared with PTH/, -TCP (15.7±2.4%), , -TCP (12.5±2.3%), DFDB (14.5±2.3%), and sham-surgery control (10.0±1.5%) at 4 weeks (p<0.014). Systemic PTH showed significantly enhanced bone formation (41.5±4.0%) compared with PTH/, -TCP (22.4±3.0%), , -TCP (21.3±4.4%), and with the sham-surgery control (23.8±4.2%) at 8 weeks (p<0.025). The DFDB group showed significantly increased bone formation from 4 (14.5±2.3%) to 8 weeks (32.0±3.2%) (p<0.006). The PTH/, -TCP and , -TCP groups both showed limited biomaterials resorption. The radiographic analysis was not diagnostic to distinguish local bone formation from the radiopaque , -TCP biomaterial. Conclusions: Systemic administration of PTH significantly stimulates local bone formation. Bone formation was significantly limited by the , -TCP biomaterial. [source] Gastric electrical activity in patients with cholelithiasis undergoing laparoscopic cholecystectomy: A prospective controlled studyJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 6 2004SPIROS N SGOUROS Abstract Background:, The aim of the present study was to evaluate the effect of gallstone disease (GD) and laparoscopic cholecystectomy on gastric electrical activity of slow waves, which was recorded via transcutaneous electrogastrography (EGG). Methods:, Twenty-one consecutive patients (M/F: 12/9, 52.7 ± 15 years old) with GD and no previous history of abdominal operations or known disease affecting gastrointestinal motility were studied. The EGG was performed for 30 min prior to and 90 min after a standard meal, during a 4,6 month period prior to and after laparoscopic cholecystectomy. The percentile proportion of the three spectra of gastric slow waves frequency was studied, defined as follows: bradygastria, 1,2.1 cycles per min (c.p.m.); normogastria, 2.2,3.9 c.p.m.; and tachygastria, 4,9 c.p.m. The findings were compared to those of nine healthy subjects (M/F: 5/4, 49.5 ± 14.8 years old). Results:, No statistically significant difference was found in percentile distribution of bradygastria, normogastria and tachygastria, pre- or post-prandially, neither before or after laparoscopic cholecystectomy, nor between patients and controls. Conclusions:, Patients with GD do not exhibit differences in gastric electrical activity of slow waves in comparison to normal subjects and laparoscopic cholecystectomy does not alter gastric electrical activity. These findings suggest that cholelithiasis does not seem to cause dyspeptic symptoms due to gastric dysrythmias. [source] Population Genetic Structure of the Medicinal Plant Vitex rotundifolia in China: Implications for its Use and ConservationJOURNAL OF INTEGRATIVE PLANT BIOLOGY, Issue 9 2008Yuan Hu Abstract Vitex rotundifolia L. is an important plant species used in traditional Chinese medicine. For its efficient use and conservation, genetic diversity and clonal variation of V. rotundifolia populations in China were investigated using inter-simple sequence repeat markers. Fourteen natural populations were included to estimate genetic diversity, and a large population with 135 individuals was used to analyze clonal variation and fine-scale spatial genetic structure. The overall genetic diversity (GD) of V. rotundifolia populations in China was moderate (GD = 0.190), with about 40% within-population variation. Across all populations surveyed, the average within-population diversity was moderate (P = 22.6%; GD = 0.086). A relatively high genetic differentiation (Gst = 0.587) among populations was detected based on the analysis of molecular variance data. Such characteristics of V. rotundifolia are likely attributed to its sexual/asexual reproduction and limited gene flow. The genotypic diversity (D = 0.992) was greater than the average values of a clonal plant, indicating its significant reproduction through seedlings. Spatial autocorrelation analysis showed a clear within-population structure with gene clusters of approximately 20 m. Genetic diversity patterns of V. rotundifolia in China provide a useful guide for its efficient use and conservation by selecting particular populations displaying greater variation that may contain required medicinal compounds, and by sampling individuals in a population at >20 m spatial intervals to avoid collecting individuals with identical or similar genotypes. [source] Body mass index, alcohol, tobacco and symptomatic gallstone disease: a Swedish twin studyJOURNAL OF INTERNAL MEDICINE, Issue 5 2007D. Katsika Abstract. Background/Aims., Both genetic and environmental factors are involved in the pathogenesis of gallstone disease (GD). We aimed to examine the association between symptomatic GD and overweight (body mass index, BMI, 25,30 kg m,2), obesity (BMI > 30 kg m,2), alcohol, smoking and smoke-free tobacco by analysing a large twin population. Methods., The Swedish Twin Registry (STR) was linked to the Swedish Hospital Discharge and Causes of Death Registries for GD and GD-surgery related diagnoses. Weight, height, use of alcohol, smoking and smoke-free tobacco were provided by STR and analysed for possible associations by conditional logistic regression. Results., Overweight and obesity were associated with a significantly higher risk for symptomatic GD in the whole study population (OR 1.86 and OR 3.38; CI: 1.52,2.28 and 2.28,5.02 respectively). High alcohol consumption was associated with a lower risk for GD in the whole population (OR 0.62; CI: 0.51,0.74) with no difference between discordant monozygotic and dizygotic twins (OR 1.08 and OR 0.96; CI: 0.82,1.42 and 0.79,1.16). Smoking or smoke-free tobacco was not correlated with GD. Conclusion., Consistent with epidemiological studies, we found positive associations between BMI and the development of symptomatic GD. High alcohol consumption was associated with a decreased risk against GD. Tobacco use has no impact on GD. [source] DNA aptamers developed against a soman derivative cross-react with the methylphosphonic acid core but not with flanking hydrophobic groupsJOURNAL OF MOLECULAR RECOGNITION, Issue 3 2009John G. Bruno Abstract Twelve rounds of systematic evolution of ligands by exponential enrichment (SELEX) were conducted against a magnetic bead conjugate of the para -aminophenylpinacolylmethylphosphonate (PAPMP) derivative of the organophosphorus (OP) nerve agent soman (GD). The goal was to develop DNA aptamers that could scavenge GD in vivo, thereby reducing or eliminating the toxic effects of this dangerous compound. Aptamers were sequenced and screened in peroxidase-based colorimetric plate assays after rounds 8 and 12 of SELEX. The aptamer candidate sequences exhibiting the highest affinity for the GD derivative from round 8 also reappeared in several clones from round 12. Each of the highest affinity PAPMP-binding aptamers also bound methylphosphonic acid (MPA). In addition, the aptamer with the highest overall affinity for PAPMP carried a sequence motif (TTTAGT) thought to bind MPA based on previously published data (J. Fluoresc 18: 867,876, 2008). This sequence motif was found in several other relatively high affinity PAPMP aptamer candidates as well. In studies with the nerve agent GD, pre-incubation of a large molar excess of aptamer candidates failed to protect human butyrylcholinesterase (BuChE) from inhibition. With the aid of three-dimensional molecular modeling of the GD derivative it appears that a hydrophilic cleft sandwiched between the pinacolyl group and the p -aminophenyl ring might channel nucleotide interactions to the phosphonate portion of the immobilized GD derivative. However, bona fide GD free in solution may be repulsed by the negative phosphate backbone of aptamers and rotate its phosphonate and fluorine moieties away from the aptamer to avoid being bound. Future attempts to develop aptamers to GD might benefit from immobilizing the pinacolyl group of bona fide GD to enhance exposure of the phosphonate and fluorine to the random DNA library. Copyright © 2008 John Wiley & Sons, Ltd. [source] Chronic Prenatal Ethanol Exposure Increases Glucocorticoid-Induced Glutamate Release in the Hippocampus of the Near-Term Foetal Guinea PigJOURNAL OF NEUROENDOCRINOLOGY, Issue 11 2006U. Iqbal Exposure to high cortisol concentration can injure the developing brain, possibly via an excitotoxic mechanism involving glutamate (Glu). The present study tested the hypothesis that chronic prenatal ethanol exposure (CPEE) activates the foetal hypothalamic-pituitary-adrenal axis to produce high cortisol exposure in the foetal compartment and alters sensitivity to glucocorticoid-induced Glu release in the foetal hippocampus. Pregnant guinea pigs received daily oral administration of ethanol (4 g/kg maternal body weight/day) or isocaloric-sucrose/pair-feeding from gestational day (GD) 2 until GD 63 (term, approximately GD 68) at which time they were euthanised, 1 h after their final treatment. Adrenocorticotrophic hormone (ACTH) and cortisol concentrations were determined in foetal plasma. Basal and electrically stimulated Glu and ,-aminobutyric acid (GABA) efflux in the presence or absence of dexamethasone (DEX), a selective glucocorticoid-receptor agonist, were determined ex vivo in foetal hippocampal slices. Glucocorticoid receptor (GR), mineralocorticoid receptor (MR) and N -methyl- d -aspartate (NMDA) receptor NR1 subunit mRNA expression were determined in situ in the hippocampus and dentate gyrus. In the near-term foetus, CPEE increased foetal plasma ACTH and cortisol concentrations. Electrically stimulated glutamate, but not GABA, release was increased in CPEE foetal hippocampal slices. Low DEX concentration (0.3 µM) decreased stimulated glutamate, but not GABA, release in both CPEE and control foetal hippocampal slices. High DEX concentration (3.0 µM) increased basal release of Glu, but not GABA, in CPEE foetal hippocampal slices. GR, but not MR, mRNA expression was elevated in the hippocampus and dentate gyrus, whereas NR1 mRNA expression was increased in the CA1 and CA3 fields of the foetal hippocampus. These data demonstrate that CPEE increases high glucocorticoid concentration-induced Glu release in the foetal hippocampus, presumably as a consequence of increased GR expression. These effects of CPEE, coupled with increased glutamate release and increased NMDA receptor expression, may predispose the near-term foetal hippocampus to GR and Glu-NMDA receptor-mediated neurodevelopmental toxicity. [source] Gender-Related Traits in Gay Men, Lesbian Women, and Heterosexual Men and Women: The Virtual Identity of Homosexual-Heterosexual Diagnosticity and Gender DiagnosticityJOURNAL OF PERSONALITY, Issue 5 2000Richard A. Lippa Three studies investigated the relationship between gender-related traits and sexual orientation. Study 1 showed that gay men and lesbians in an unselected sample of 721 college students differed from same-sex heterosexuals most strongly on gender diagnosticity (GD) measures, which assess male- versus female-typicality of interests (effect sizes of 2.70 for men and .96 for women) and least strongly on measures of instrumentality (I) and expressiveness (E). In Study 2, GD measures showed large differences between 95 gay and 136 heterosexual men (effect sizes of 1.61 and 1.83) and between 46 lesbian and 225 heterosexual women (effect sizes of .98 and 1.28), whereas I and E showed much smaller differences. In Study 3, GD showed large differences between 90 gay and 81 heterosexual men (effect sizes of 1.76 and 1.97) and between 82 lesbians and 108 heterosexual women (effect sizes 1.67 and 1.70), whereas I and E showed much smaller differences. Using data from Studies 2 and 3, ,gay-heterosexual diagnosticity' measures were computed for men and ,lesbian-heterosexual diagnosticity' measures for women, based on occupational and hobby preferences. These measures correlated very strongly with GD measures. [source] Magnetic Resonance Microscopy Defines Ethanol-Induced Brain Abnormalities in Prenatal Mice: Effects of Acute Insult on Gestational Day 7ALCOHOLISM, Issue 1 2010Elizabeth A. Godin Background:, This magnetic resonance microscopy (MRM)-based report is the second in a series designed to illustrate the spectrum of craniofacial and central nervous system (CNS) dysmorphia resulting from single- and multiple-day maternal ethanol treatment. The study described in this report examined the consequences of ethanol exposure on gestational day (GD) 7 in mice, a time in development when gastrulation and neural plate development begins; corresponding to the mid- to late third week postfertilization in humans. Acute GD 7 ethanol exposure in mice has previously been shown to result in CNS defects consistent with holoprosencephaly (HPE) and craniofacial anomalies typical of those in Fetal Alcohol Syndrome (FAS). MRM has facilitated further definition of the range of GD 7 ethanol-induced defects. Methods:, C57Bl/6J female mice were intraperitoneally (i.p.) administered vehicle or 2 injections of 2.9 g/kg ethanol on day 7 of pregnancy. Stage-matched control and ethanol-exposed GD 17 fetuses selected for imaging were immersion fixed in a Bouins/Prohance solution. MRM was conducted at either 7.0 Tesla (T) or 9.4 T. Resulting 29 ,m isotropic spatial resolution scans were segmented and reconstructed to provide 3D images. Linear and volumetric brain measures, as well as morphological features, were compared for control and ethanol-exposed fetuses. Following MRM, selected specimens were processed for routine histology and light microscopic examination. Results:, Gestational day 7 ethanol exposure resulted in a spectrum of median facial and forebrain deficiencies, as expected. This range of abnormalities falls within the HPE spectrum; a spectrum for which facial dysmorphology is consistent with and typically is predictive of that of the forebrain. In addition, other defects including median facial cleft, cleft palate, micrognathia, pituitary agenesis, and third ventricular dilatation were identified. MRM analyses also revealed cerebral cortical dysplasia/heterotopias resulting from this acute, early insult and facilitated a subsequent focused histological investigation of these defects. Conclusions:, Individual MRM scans and 3D reconstructions of fetal mouse brains have facilitated demonstration of a broad range of GD 7 ethanol-induced morphological abnormality. These results, including the discovery of cerebral cortical heterotopias, elucidate the teratogenic potential of ethanol insult during the third week of human prenatal development. [source] Magnetic Resonance Microscopy Defines Ethanol-Induced Brain Abnormalities in Prenatal Mice: Effects of Acute Insult on Gestational Day 8ALCOHOLISM, Issue 6 2009Scott E. Parnell Background:, Magnetic resonance microscopy (MRM), magnetic resonance imaging (MRI) at microscopic levels, provides unprecedented opportunities to aid in defining the full spectrum of ethanol's insult to the developing brain. This is the first in a series of reports that, collectively, will provide an MRM-based atlas of developmental stage-dependent structural brain abnormalities in a Fetal Alcohol Spectrum Disorders (FASD) mouse model. The ethanol exposure time and developmental stage examined for this report is gestational day (GD) 8 in mice, when the embryos are at early neurulation stages; stages present in humans early in the fourth week postfertilization. Methods:, For this study, pregnant C57Bl/6J mice were administered an ethanol dosage of 2.8 g/kg intraperitoneally at 8 days, 0 hour and again at 8 days, 4 hours postfertilization. On GD 17, fetuses that were selected for MRM analyses were immersion fixed in a Bouin's/Prohance® solution. Control fetuses from vehicle-treated dams were stage-matched to those that were ethanol-exposed. The fetal mice were scanned ex vivo at 7.0 T and 512 × 512 × 1024 image arrays were acquired using 3-D spin warp encoding. The resulting 29 ,m (isotropic) resolution images were processed using ITK-SNAP, a 3-D segmentation/visualization tool. Linear and volume measurements were determined for selected brain, head, and body regions of each specimen. Comparisons were made between control and treated fetuses, with an emphasis on determining (dis)proportionate changes in specific brain regions. Results:, As compared with controls, the crown-rump lengths of stage-matched ethanol-exposed GD 17 fetuses were significantly reduced, as were brain and whole body volumes. Volume reductions were notable in every brain region examined, with the exception of the pituitary and septal region, and were accompanied by increased ventricular volumes. Disproportionate regional brain volume reductions were most marked on the right side and were significant for the olfactory bulb, hippocampus, and cerebellum; the latter being the most severely affected. Additionally, the septal region and the pituitary were disproportionately large. Linear measures were consistent with those of volume. Other dysmorphologic features noted in the MR scans were choanal stenosis and optic nerve coloboma. Conclusions:, This study demonstrates that exposure to ethanol occurring in mice at stages corresponding to the human fourth week postfertilization results in structural brain abnormalities that are readily identifiable at fetal stages of development. In addition to illustrating the utility of MR microscopy for analysis of an FASD mouse model, this work provides new information that confirms and extends human clinical observations. It also provides a framework for comparison of structural brain abnormalities resulting from ethanol exposure at other developmental stages and dosages. [source] Ethanol-Mediated Fetal Dysmorphology and its Relationship to the Ontogeny of Maternal Liver MetallothioneinALCOHOLISM, Issue 6 2009Peter Coyle Background:, Fetal zinc (Zn) deficiency arising from ethanol-induction of the Zn-binding protein metallothionein (MT) in the mother's liver has been proposed as a mechanism of teratogenicity. Here, we determine the ontogeny of MT and Zn homeostasis in rats and mice and then examine the effect of acute ethanol exposure in early embryonic development on this relationship. The protective effect of Zn against ethanol-mediated fetal dysmorphology is also examined. Methods:, Study 1: Maternal liver MT and Zn homeostasis was determined in Sprague,Dawley rats and C57BL/6J mice throughout gestation. Study 2: Rats were administered ethanol (25% in saline, intraperitoneal 0.015 ml/g) or vehicle alone on gestational day (GD) 9. Maternal liver MT and Zn, and plasma Zn was determined over the ensuing 24 hours. Study 3: Pregnant rats were treated with ethanol and Zn (s.c. 2.5 ,g Zn/g) on GD9 and fetal dysmorphology was assessed on GD 19. Results:, Study 1: Maternal liver MT began to rise around GD 9 peaking on GD 15 before falling to nonpregnant levels around term. The pregnancy-related increase in MT was associated with a fall in plasma Zn which was significantly lower on GD 15 thereafter returning to nonpregnant levels by parturition. Study 2: Ethanol administered to pregnant rats on GD 9 resulted in a 10-fold induction of MT in the maternal liver and was associated with a 33% rise in liver Zn and a 30% fall in plasma Zn, 16 hours after treatment. Study 3: Ethanol treatment on GD 9 resulted in a significant increase in craniofacial malformations which were prevented by concurrent Zn treatment. Conclusions:, The findings indicate that maternal liver MT levels are lowest in early gestation (before GD 10) making this a sensitive period where ethanol-induction of MT can affect fetal Zn homeostasis and cause fetal dysmorphology. The study further provides evidence of a protective role for Zn against ethanol-mediated teratogenicity. [source] Dietary Zinc Supplementation Throughout Pregnancy Protects Against Fetal Dysmorphology and Improves Postnatal Survival After Prenatal Ethanol Exposure in MiceALCOHOLISM, Issue 4 2009Brooke L. Summers Background:, We have previously demonstrated that ethanol teratogenicity is associated with metallothionein-induced fetal zinc (Zn) deficiency, and that maternal subcutaneous Zn treatment given with ethanol in early pregnancy prevents fetal abnormalities and spatial memory impairments in mice. Here we investigated whether dietary Zn supplementation throughout pregnancy can also prevent ethanol-related dysmorphology. Methods:, Pregnant mice were injected with saline or 25% ethanol (0.015 ml/g intraperitoneally at 0 and 4 hours) on gestational day (GD) 8 and fed either a control (35 mg Zn/kg) or a Zn-supplemented diet (200 mg Zn/kg) from GD 0 to 18. Fetuses from the saline, saline + Zn, ethanol and ethanol + Zn groups were assessed for external birth abnormalities on GD 18. In a separate cohort of mice, postnatal growth and survival of offspring from these treatment groups were examined from birth until postnatal day 60. Results:, Fetuses from dams treated with ethanol alone in early pregnancy had a significantly greater incidence of physical abnormalities (26%) compared to those from the saline (10%), saline + Zn (9%), or ethanol + Zn (12%) groups. The incidence of abnormalities in ethanol + Zn-supplemented fetuses was not different from saline-treated fetuses. While ethanol exposure did not affect the number of fetal resorptions or pre- or postnatal weight, there were more stillbirths with ethanol alone, and cumulative postnatal mortality was significantly higher in offspring exposed to ethanol alone (35% deaths) compared to all other treatment groups (13.5 to 20.5% deaths). Mice supplemented with Zn throughout pregnancy had higher plasma Zn concentrations than those in un-supplemented groups. Conclusions:, These findings demonstrate that dietary Zn supplementation throughout pregnancy ameliorates dysmorphology and postnatal mortality caused by ethanol exposure in early pregnancy. [source] Maternal Oral Intake Mouse Model for Fetal Alcohol Spectrum Disorders: Ocular Defects as a Measure of EffectALCOHOLISM, Issue 10 2006Scott E. Parnell Background: This work was conducted in an effort to establish an oral intake model system in which the effects of ethanol insult that occur during early stages of embryogenesis can be easily examined and in which agents that may modulate ethanol's teratogenicity can be readily tested in vivo. The model system described utilizes the alcohol deprivation effect to obtain teratogenic levels of maternal ethanol intake on days 7 and 8 of pregnancy in C57Bl/6J mice. Ocular defects including microphthalmia and uveal coloboma, which have previously been shown to result from ethanol administered by gavage or via intraperitoneal injection on these days, served as the developmental end point for this study. The ocular defects are readily identifiable and their degree of severity is expected to correlate with concurrently developing defects of the central nervous system (CNS). Methods: Female C57Bl/6J mice were maintained on an ethanol-containing (4.8% v/v) liquid diet for 14 days and then mated during a subsequent abstinence period. Mice were then reexposed to ethanol on days 7 and 8 of pregnancy only. Control as well as ethanol-exposed dams were killed on their 14th day of pregnancy. Fetuses were then weighed, measured for crown rump length, photographed, and analyzed for ocular abnormalities. Globe size, palpebral fissure length, and pupil size and shape were noted for both the right and left eyes of all fetuses and informative comparisons were made. Results: This exposure paradigm resulted in peak maternal blood alcohol concentrations that ranged from 170 to 220 mg/dL on gestational day (GD) 8. Compared with the GD 14 fetuses from the normal control group, the pair-fed, acquisition controls, as well as the ethanol-exposed fetuses, were developmentally delayed and had reduced weights. Confirming previous studies, comparison of similarly staged control and treated GD 8 embryos illustrated reductions in the size of the forebrain in the latter. Subsequent ocular malformations were noted in 33% of the right eyes and 25% of the left eyes of the 103 GD 14 ethanol-exposed fetuses examined. This incidence of defects is twice that observed in the control groups. Additionally, it was found that the palpebral fissure length is directly correlated with globe size. Conclusions: The high incidence of readily identifiable ocular malformations produced by oral ethanol intake in this model and their relevance to human fetal alcohol spectrum disorders (FASD) makes this an excellent system for utilization in experiments involving factors administered to the embryo that might alter ethanol's teratogenic effects. Additionally, the fact that early ethanol insult yields ocular and forebrain abnormalities that are developmentally associated allows efficient specimen selection for subsequent detailed analyses of CNS effects in this in vivo mammalian FASD model. [source] Fetal Learning With Ethanol: Correlations Between Maternal Hypothermia During Pregnancy and Neonatal Responsiveness to Chemosensory Cues of the DrugALCOHOLISM, Issue 5 2004Paula Abate Abstract: Background: Fetuses learn about ethanol odor when the drug is present in the amniotic fluid. Prenatal learning comprising ethanol's chemosensory cues also suggests an acquired association between ethanol's chemosensory and postabsorptive properties. Ethanol-related thermal disruptions have been implicated as a significant component of the drug's unconditioned properties. In the present study, ethanol-induced thermal changes were analyzed in pregnant rats subjected to a moderate ethanol dose. This thermal response was later tested for its correlation with the responsiveness of the progeny to ethanol and nonethanol chemosensory stimuli. Methods: During gestational day (GD) 14, pregnant rats were subjected to a minor surgical procedure to place a subcutaneous telemetric thermal sensor in the nape of the neck. During GDs 17 to 20, females received a daily intragastric administration of ethanol (2 g/kg) or water, using solutions kept at room temperature. Maternal body temperatures were recorded before and after (4 consecutive hours) the administration of water or ethanol. Newborns representative of both prenatal treatments were tested in terms of behavioral activity elicited by the smell of ethanol or of a novel odorant (cineole). A third group of pups were tested in response to unscented air stimulation. Results: Ethanol administration during late gestation induced reliable maternal hypothermia, a thermal disruption greater than that observed in water-treated females. It was systematically observed that maternal ethanol-induced hypothermia negatively correlated with neonatal motor reactivity elicited by ethanol olfactory stimulation. No other significant correlations were observed in terms of responsiveness to cineole or to unscented air in animals prenatally exposed to ethanol or water. Conclusions: In conjunction with prior research, the present results indicate that fetal ethanol exposure may yield learning of an association between ethanol's sensory and unconditioned properties. Ethanol-induced hypothermia during late gestation seems to represent a significant component of ethanol's unconditioned consequences. Specifically, ethanol-related thermal disruptions in the womb are highly predictive of neonatal responsiveness to ethanol's chemosensory cues that are known to be processed by the near-term fetus. [source] | |||||||||||||||||||||||||