A Comparative In Vitro Metabolic Study of Certain Pesticidal Phenyl N-Methyl-Carbamates

Two critical parameters in the evaluation of the toxicological hazards of the use of carbamate pesticides are: (1) a rapid, sensitive, and precise analytical method of identification of the carbamate and its metabolites; and (2) their metabolism. A method in this study was developed whereby various carbamates and their metabolites could be chromatographed in the gaseous phase. Also, a comparative in vitro study of 15,000 g liver supernatants from human, rat, and dog was performed. Additional tissues investigated for metabolic activity toward the carbamates, Zectran and Mesurol, were kidney (from the dog only) and various blood fractions (red blood cells, serum and whole blood). The various homogenates from the liver and kidney were ether-extracted after incubation. The ether extract was processed and spotted on silica gel G thin-layer chromatographic plates and developed bidimensionally to resolve metabolites. Radioautographic analysis was used to identify the radioactive areas. After incubation the blood was treated in a similar manner as the liver and kidney homogenates. It was found that, in vitro, the liver was the major site of metabolism, and that the oxidative enzymes mediated by the NADPH mixed oxidase system were the major participants in the metabolism of Zectran and Mesurol. These enzymes utilized primarily non-hydrolytic pathways in the processes of degradation. The main metabolite produced with Zectran was 4-methylamino-3,5-xylyl N methylcarbamate (MA). Minor metabolites produced were 4-dimethylamino-3,5-xylyl N hydroxy methylcarbamate (NOHME), 4-methylformamido-3,5-xylyl-N methylcarbamate and 4-formamido-3,5-xylyl N methylcarbamate. The rat and the dog produced eight times as much NOHME as the human. 4-methylsulfinyl-3,5-xylyl N methylcarbamate (sulfoxide) · and 4-methylthio-3,5-xylyl N-methylcarbamate (NOHME) were the major metabolites produced with Mesurol. The human and the rat produced four times· as much NOHME as the dog. These examples demonstrate the wide interspecies variation prevalent in Zectran and Mesurol metabolism. These data indicate that N-dealkylation is the major route of metabolism for Zectran in all three species. Minor pathways included hydroxylation of the carbamate moiety N-methyl groups. Sulfoxidation and hydroxylation were the major routes of metabolism with Mesurol in all three species. The kidney and blood possessed very low hydrolytic and nonhydrolytic metabolic activity

Parenting Self-Efficacy and Parenting Practices over Time in Mexican American Families

Drawing on social cognitive theory, this study used a longitudinal cross-lagged panel design and a structural equation modeling approach to evaluate parenting self-efficacy\u27s reciprocal and causal associations with parents\u27 positive control practices over time to predict adolescents\u27 conduct problems. Data were obtained from teachers, mothers, and adolescents in 189 Mexican American families living in the southwest U.S. After accounting for contemporaneous reciprocal relationships between parenting self-efficacy (PSE) and positive control, results indicated that parenting self-efficacy predicted future positive control practices rather than the reverse. PSE also showed direct effects on decreased adolescent conduct problems. PSE functioned in an antecedent causal role in relation to parents\u27 positive control practices and adolescents\u27 conduct problems in this sample. These results support the cross-cultural applicability of social cognitive theory to parenting in Mexican American families. An implication is that parenting interventions aimed at preventing adolescent conduct problems need to focus on elevating the PSE of Mexican American parents with low levels of PSE. In addition, future research should seek to specify the most effective strategies for enhancing PSE

Family Influences on Mexican American Adolescents’ Romantic Relationships: Moderation by Gender and Culture

This study examined prospective associations between the family context and adolescents’ romantic relationships as moderated by adolescents’ gender and culture among Mexican American families (N = 189). Adolescents at Time 1 (early adolescence) were on average 12.29 years of age (SD = .50) and 54% female. Mothers and fathers reported on family structure and dynamics during early adolescence, and youth reported on their romantic relationship involvement and quality during middle and late adolescence. Results from path analyses indicated that family structure and dynamics (supportive parenting, consistent discipline, parent-adolescent, and interparental conflict) were associated with adolescents’ romantic involvement and quality, with differences by adolescents’ gender and culture. Findings highlight Mexican American family contexts that contribute uniquely to adolescents’ romantic relationships

Brimonidine prevents axonal and somatic degeneration of retinal ganglion cell neurons

<p>Abstract</p> <p>Background</p> <p>Brimonidine is a common drug for lowering ocular pressure and may directly protect retinal ganglion cells in glaucoma. The disease involves early loss of retinal ganglion cell transport to brain targets followed by axonal and somatic degeneration. We examined whether brimonidine preserves ganglion cell axonal transport and abates degeneration in rats with elevated ocular pressure induced by laser cauterization of the episcleral veins.</p> <p>Results</p> <p>Ocular pressure was elevated unilaterally by 90% for a period of 8 weeks post- cauterization. During this time, brimonidine (1mg/kg/day) or vehicle (phosphate-buffered saline) was delivered systemically and continuously via subcutaneous pump. Animals received bilateral intravitreal injections of fluorescent cholera toxin subunit β (CTB) two days before sacrifice to assess anterograde transport. In retinas from the vehicle group, elevated pressure induced a 44% decrease in the fraction of ganglion cells with intact uptake of CTB and a 14-42% reduction in the number of immuno-labelled ganglion cell bodies, with the worst loss occurring nasally. Elevated pressure also caused a 33% loss of ganglion cell axons in vehicle optic nerves and a 70% decrease in CTB transport to the superior colliculus. Each of these components of ganglion cell degeneration was either prevented or significantly reduced in the brimonidine treatment group.</p> <p>Conclusions</p> <p>Continuous and systemic treatment with brimonidine by subcutaneous injection significantly improved retinal ganglion cell survival with exposure to elevated ocular pressure. This effect was most striking in the nasal region of the retina. Brimonidine treatment also preserved ganglion cell axon morphology, sampling density and total number in the optic nerve with elevated pressure. Consistent with improved outcome in the optic projection, brimonidine also significantly reduced the deficits in axonal transport to the superior colliculus associated with elevated ocular pressure. As transport deficits to and from retinal ganglion cell projection targets in the brain are relevant to the progression of glaucoma, the ability of brimonidine to preserve optic nerve axons and active transport suggests its neuroprotective effects are relevant not only at the cell body, but throughout the entire optic projection.</p

Genomic regions associated with kyphosis in swine

<p>Abstract</p> <p>Background</p> <p>A back curvature defect similar to kyphosis in humans has been observed in swine herds. The defect ranges from mild to severe curvature of the thoracic vertebrate in split carcasses and has an estimated heritability of 0.3. The objective of this study was to identify genomic regions that affect this trait.</p> <p>Results</p> <p>Single nucleotide polymorphism (SNP) associations performed with 198 SNPs and microsatellite markers in a Duroc-Landrace-Yorkshire resource population (U.S. Meat Animal Research Center, USMARC resource population) of swine provided regions of association with this trait on 15 chromosomes. Positional candidate genes, especially those involved in human skeletal development pathways, were selected for SNP identification. SNPs in 16 candidate genes were genotyped in an F2 population (n = 371) and the USMARC resource herd (n = 1,257) with kyphosis scores. SNPs in <it>KCNN2 </it>on SSC2, <it>RYR1 </it>and <it>PLOD1 </it>on SSC6 and <it>MYST4 </it>on SSC14 were significantly associated with kyphosis in the resource population of swine (<it>P </it>≤ 0.05). SNPs in <it>CER1 </it>and <it>CDH7 </it>on SSC1, <it>PSMA5 </it>on SSC4, <it>HOXC6 </it>and <it>HOXC8 </it>on SSC5, <it>ADAMTS18 </it>on SSC6 and <it>SOX9 </it>on SSC12 were significantly associated with the kyphosis trait in the F2 population of swine (<it>P </it>≤ 0.05).</p> <p>Conclusions</p> <p>These data suggest that this kyphosis trait may be affected by several loci and that these may differ by population. Carcass value could be improved by effectively removing this undesirable trait from pig populations.</p

Evaluation of Bovine chemerin (RARRES2) Gene Variation on Beef Cattle Production Traits1

A previous study in cattle based on >48,000 markers identified markers on chromosome 4 near the chemerin gene associated with average daily feed intake (ADFI) in steers (P < 0.008). Chemerin is an adipokine associated with obesity and metabolic syndrome in humans, representing a strong candidate gene potentially underlying the observed association. To evaluate whether the bovine chemerin gene is involved in feed intake, 16 markers within and around the gene were tested for association in the same resource population. Eleven were nominally significant for ADFI (P < 0.05) and two were significant after Bonferroni correction. Two and five SNP in this region were nominally significant for the related traits of average daily gain (ADG) and residual feed intake (RFI), respectively. All markers were evaluated for effects on meat quality and carcass phenotypes. Many of the markers associated with ADFI were associated with hot carcass weight (HCW), adjusted fat thickness (AFT), and marbling (P < 0.05). Marker alleles that were associated with lower ADFI were also associated with lower HCW, AFT, and marbling. Markers associated with ADFI were genotyped in a validation population of steers representing 14 breeds to determine predictive merit across populations. No consistent relationships for ADFI were detected. To determine whether cattle feed intake or growth phenotypes might be related to chemerin transcript abundance, the expression of chemerin was evaluated in adipose of 114 heifers that were siblings of the steers in the discovery population. Relative chemerin transcript abundance was not correlated with ADFI, ADG, or RFI, but associations with body condition score and yearling weight were observed. We conclude that variation in the chemerin gene may underlie observed association in the resource population, but that additional research is required to determine if this variation is widespread among breeds and to develop robust markers with predictive merit across breeds

Association, effects and validation of polymorphisms within the NCAPG - LCORL locus located on BTA6 with feed intake, gain, meat and carcass traits in beef cattle

<p>Abstract</p> <p>Background</p> <p>In a previously reported genome-wide association study based on a high-density bovine SNP genotyping array, 8 SNP were nominally associated (<it>P </it>≤ 0.003) with average daily gain (ADG) and 3 of these were also associated (<it>P </it>≤ 0.002) with average daily feed intake (ADFI) in a population of crossbred beef cattle. The SNP were clustered in a 570 kb region around 38 Mb on the draft sequence of bovine chromosome 6 (BTA6), an interval containing several positional and functional candidate genes including the bovine <it>LAP3, NCAPG</it>, and <it>LCORL </it>genes. The goal of the present study was to develop and examine additional markers in this region to optimize the ability to distinguish favorable alleles, with potential to identify functional variation.</p> <p>Results</p> <p>Animals from the original study were genotyped for 47 SNP within or near the gene boundaries of the three candidate genes. Sixteen markers in the <it>NCAPG-LCORL </it>locus displayed significant association with both ADFI and ADG even after stringent correction for multiple testing (P ≤ 005). These markers were evaluated for their effects on meat and carcass traits. The alleles associated with higher ADFI and ADG were also associated with higher hot carcass weight (HCW) and ribeye area (REA), and lower adjusted fat thickness (AFT). A reduced set of markers was genotyped on a separate, crossbred population including genetic contributions from 14 beef cattle breeds. Two of the markers located within the <it>LCORL </it>gene locus remained significant for ADG (P ≤ 0.04).</p> <p>Conclusions</p> <p>Several markers within the <it>NCAPG-LCORL </it>locus were significantly associated with feed intake and body weight gain phenotypes. These markers were also associated with HCW, REA and AFT suggesting that they are involved with lean growth and reduced fat deposition. Additionally, the two markers significant for ADG in the validation population of animals may be more robust for the prediction of ADG and possibly the correlated trait ADFI, across multiple breeds and populations of cattle.</p