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1.
G3 (Bethesda) ; 8(8): 2841-2854, 2018 07 31.
Article in English | MEDLINE | ID: mdl-29967054

ABSTRACT

The availability of high-density molecular markers in common bean has allowed to explore the genetic basis of important complex agronomic traits with increased resolution. Genome-Wide Association Studies (GWAS) and Regional Heritability Mapping (RHM) are two analytical approaches for the detection of genetic variants. We carried out GWAS and RHM for plant architecture, lodging and productivity across two important growing environments in Brazil in a germplasm of 188 common bean varieties using DArTseq genotyping strategies. The coefficient of determination of G × E interaction (c2int ) was equal to 17, 21 and 41%, respectively for the traits architecture, lodging, and productivity. Trait heritabilities were estimated at 0.81 (architecture), 0.79 (lodging) and 0.43 (productivity), and total genomic heritability accounted for large proportions (72% to ≈100%) of trait heritability. At the same probability threshold, three marker-trait associations were detected using GWAS, while RHM detected eight QTL encompassing 145 markers along five chromosomes. The proportion of genomic heritability explained by RHM was considerably higher (35.48 to 58.02) than that explained by GWAS (28.39 to 30.37). In general, RHM accounted for larger fractions of the additive genetic variance being captured by markers effects inside the defined regions. Nevertheless, a considerable proportion of the heritability is still missing (∼42% to ∼64%), probably due to LD between markers and genes and/or rare allele variants not sampled. RHM in autogamous species had the potential to identify larger-effect QTL combining allelic variants that could be effectively incorporated into whole-genome prediction models and tracked through breeding generations using marker-assisted selection.


Subject(s)
Chromosome Mapping , Genome-Wide Association Study , Inheritance Patterns , Phaseolus/genetics , Quantitative Trait, Heritable , Algorithms , Alleles , Gene Expression Regulation, Plant , Genetic Markers , Genomics , Genotype , Linkage Disequilibrium , Models, Genetic , Phaseolus/classification , Phenotype , Quantitative Trait Loci
2.
Issues Ment Health Nurs ; 22(5): 503-16, 2001.
Article in English | MEDLINE | ID: mdl-11881512

ABSTRACT

This paper describes a 22-hour domestic violence learning module that is incorporated into the psychosocial course for seniors in a baccalaureate nursing program. As part of their learning experiences, students attend circuit court, meet with judges, and accompany advocacy workers. Additionally, they attend group therapy sessions with both the victims and perpetrators of abuse. Students keep journals reflecting their thoughts, feelings, and reactions throughout the experiences. Thematic analysis of these journal entries revealed five common themes. Students recognized their encounters in clinical situations as frightening and emotionally difficult, expressed surprise at their reactions to perpetrators, identified with victims, wrestled with issues of good and bad, and reported that stereotypes about victims and perpetrators had been incorrect. Debriefings and support by faculty are important for students throughout the experience.


Subject(s)
Education, Nursing, Baccalaureate , Psychiatric Nursing/education , Spouse Abuse/rehabilitation , Adult , Curriculum , Female , Humans , Male , Nurse-Patient Relations , Spouse Abuse/psychology
3.
JPEN J Parenter Enteral Nutr ; 24(3): 159-63, 2000.
Article in English | MEDLINE | ID: mdl-10850941

ABSTRACT

BACKGROUND: Mitogen-activated protein kinase (MAPK) cascades represent a major signal system to transduce extracellular signals into cellular responses. Overactivity of MAPK has been implicated in the development of many diseases, including cancer and sepsis. This study investigated the hypothesis that fish oil altered the membrane phospholipid composition and modulated MAPK activity. METHODS: RAW 264.7 cells, a mouse macrophage (Mphi) cell line, were grown in eicosapentaenoic acid (EPA)-rich media (114 micromol/L) for 48 hours. Mphi were washed and exposed to Escherichia coli lipopolysaccharide (LPS; 1 microg/mL) for 10 minutes. Both total and activated (phosphorylated) portions of MAPK (P44 and P42) were determined by Western blot assays. AP-1 transcription factor activity was determined by electrophoretic mobility gel shift assays (EMSA). Mphi tumor necrosis factor (TNF) mRNA expression was measured by Northern blot assays. RESULTS: LPS stimulation induced RAW cell phosphorylation of P44/P42. In contrast, RAW cells grown in EPA-rich media had less P44/P42 activation in the presence of LPS. Total P44/P42 were not affected by EPA or LPS. Similarly, EPA also inhibited AP-1 activity. Inhibition of P44/P42 activity with PD98059 reduced both AP-1 activity and TNF mRNA expression of LPS-stimulated Mphi. CONCLUSIONS: Our data suggest that fish oil regulates macrophage proinflammatory gene activation, at least in part, by modulating the MAPK activity.


Subject(s)
Fish Oils/pharmacology , Macrophages/physiology , Mitogen-Activated Protein Kinases/metabolism , Animals , Arachidonic Acids , Blotting, Western , Cell Line , Down-Regulation , Electrophoresis , Escherichia coli , Lipopolysaccharides/pharmacology , Macrophages/drug effects , Macrophages/enzymology , Membrane Lipids/chemistry , Mice , Mitogen-Activated Protein Kinases/drug effects , RNA, Messenger , Tumor Necrosis Factor-alpha/biosynthesis , Tumor Necrosis Factor-alpha/genetics
4.
J Surg Res ; 86(1): 103-7, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10452875

ABSTRACT

BACKGROUND: Fish oil-supplemented diets have anti-inflammatory and immunomodulating effects. Although fish oil is readily incorporated into the cell membrane and influences the production of eicosanoids, the exact mechanism is not clear. This study was designed to investigate the effects of eicosapentaenoic acid (EPA), a major component of fish oil, on macrophage (Mphi) cyclooxygenase (COX) gene expression induced by LPS. METHODS: RAW 264.7 cells, a mouse Mphi cell line, were grown in EPA-rich media for 24 h. Mphi were washed and exposed to Escherichia coli LPS (10 microg/ml). Membrane lipid profile was determined by gas chromatographic analysis. COX-1 and COX-2 mRNA expressions were determined by Northern blot assays with mouse-specific cDNA probes. PGE(2) production of Mphi was measured by ELISA. Mphi production of COX-2 protein was determined by Western blot assays with an anti-COX-2 antibody. RESULTS: Incubation in EPA-rich media increased membrane EPA and decreased arachidonic acid (AA) composition. COX-2 mRNA expression was induced by EPA and further augmented by LPS stimulation. EPA also augmented Mphi production of COX-2 protein. In comparison, COX-1 mRNA expression was not affected by either LPS stimulation or EPA incubation. EPA reduced PGE(2) production by LPS-stimulated Mphi. To further support that COX-2 mRNA was regulated by COX product, exogenous PGE(2) was added to Mphi prior to LPS stimulation. PGE(2) reduced COX-2 mRNA of LPS-stimulated Mphi. CONCLUSION: EPA displaces AA and reduces PGE(2) production by LPS-stimulated Mphi. Fish oil inhibition of Mphi PGE(2) production induces COX-2 mRNA expression through a COX-2 product-mediated feedback mechanism.


Subject(s)
Endotoxins/pharmacology , Fish Oils/pharmacology , Gene Expression/drug effects , Isoenzymes/genetics , Macrophages/enzymology , Prostaglandin-Endoperoxide Synthases/genetics , Animals , Cell Line , Cyclooxygenase 2 , Dinoprostone/biosynthesis , Dinoprostone/pharmacology , Drug Synergism , Eicosapentaenoic Acid/pharmacology , Isoenzymes/metabolism , Lipopolysaccharides/pharmacology , Mice , Prostaglandin-Endoperoxide Synthases/metabolism , RNA, Messenger/metabolism
5.
J Surg Res ; 82(2): 216-21, 1999 Apr.
Article in English | MEDLINE | ID: mdl-10090832

ABSTRACT

BACKGROUND: Fish oil-supplemented diets have anti-inflammatory and immunomodulating effects, though the exact mechanism(s) are unknown. This study investigated the effects of eicosapentanenoic acid (EPA), a major component of fish oil, on transcriptional regulation of tumor necrosis factor (TNF) gene in lipopolysaccharide (LPS)-stimulated macrophages (MO). METHODS: RAW 264.7 cells, a mouse MO cell line, were grown in EPA-rich media for 24-48 h. MO were washed and exposed to Escherichia coli LPS (1 microg/ml) for 2 h. TNF mRNA expression was measured by Northern blot assays. Total nuclear extracts were harvested for the measurement of NF kappa B with electrophoretic mobility shift assays. Supershift assays were performed with anti-P50 or anti-P65 antibodies to show components of NF kappa B dimers. TNF production was determined by L929 bioassays. RESULTS: LPS stimulated RAW cell TNF mRNA expression and NF kappa B activity. In contrast, RAW cells grown in EPA-rich media had less TNF mRNA expression and an altered composition of the NF kappa B subunits (P65/P50 dimers) in the presence of LPS. TNF production by LPS-stimulated MO was reduced by EPA. CONCLUSIONS: The inhibitory effect of EPA on LPS-stimulated MO TNF gene transcription and protein elaboration is, in part, mediated through altering NF kappa B activation by reducing the P65/P50 dimers.


Subject(s)
Eicosapentaenoic Acid/pharmacology , Fish Oils/pharmacology , Macrophages/physiology , NF-kappa B/physiology , Transcription, Genetic/drug effects , Tumor Necrosis Factor-alpha/genetics , Animals , Cell Line , Cell Membrane/metabolism , Escherichia coli , Fatty Acids/metabolism , Lipopolysaccharides/pharmacology , Macrophages/drug effects , Macrophages/metabolism , Mice , RNA, Messenger/metabolism , Tumor Necrosis Factor-alpha/biosynthesis
6.
Ultrasound Med Biol ; 24(9): 1357-67, 1998 Nov.
Article in English | MEDLINE | ID: mdl-10385959

ABSTRACT

The aim of this study was to investigate whether or not a magnetic position sensing system for free-hand acquisition of 3-D ultrasound images could be used to estimate liver volumes, and to study the effect of a high-caloric meal on these volumes in healthy subjects. In vitro accuracy was evaluated by scanning porcine and rabbit livers. Ten healthy subjects were examined fasting and 30 min after ingesting a high-caloric liquid meal. Portal and hepatic vein blood flow were measured by 2-D duplex sonography. The 3-D system yielded a strong correlation (r = 0.99) between true and estimated volumes in vitro. No significant increase in liver volume in response to the meal was seen. However, portal and hepatic vein flow volume increased significantly. Experience in human subjects suggests that a complete 3-D study of liver volumes can be obtained from multiple acoustic windows. In healthy subjects, no significant increase in liver volume was seen in response to ingestion of a high-caloric liquid meal.


Subject(s)
Food, Formulated , Liver/diagnostic imaging , Adult , Animals , Energy Intake , Humans , Image Processing, Computer-Assisted , Liver/anatomy & histology , Liver Circulation , Male , Rabbits , Swine , Ultrasonography/methods
7.
J Surg Res ; 71(1): 54-60, 1997 Jul 15.
Article in English | MEDLINE | ID: mdl-9271278

ABSTRACT

Liver ischemia and reperfusion injury is mediated by oxygen free radicals, cytokines, and prostanoids produced by Kupffer cells and infiltrating neutrophils. Fish oil-supplemented diets alter membrane phospholipid composition and modify prostanoids and cytokine production in response to ischemia and reperfusion. This study tested the hypothesis that a fish oil-supplemented diet would attenuate warm liver ischemia and reperfusion injury in the rat. Male Sprague-Dawley rats were fed Vital HN supplemented with either fish oil (FO) or corn oil (CO) by the continuous duodenal infusion for 5 days. Total dietary fat (26% of total calories), caloric intake (70 cal/day), and volume (60 ml/day) were identical between two groups. Plasma eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) levels increased significantly in rats fed fish oil (0 to 16.3% for EPA and 2 to 12% for DHA). Liver histology was similar in both groups before ischemia. On Day 6, rats were subjected to 60 min of reversible hepatic ischemia. Plasma TNF levels, 1 and 24 hr after reperfusion, were not different between FO and CO rats. Liver injury assessed by bile flow, histology, plasma ALT, and bile glutathione efflux did not differ between groups. We conclude that our fish oil-supplemented enteral diet does not attenuate warm liver ischemia and reperfusion injury in rats.


Subject(s)
Fish Oils/administration & dosage , Liver/blood supply , Reperfusion Injury/prevention & control , Alanine Transaminase/blood , Animals , Bile/metabolism , Body Weight , Dietary Fats/metabolism , Glutathione/metabolism , Ischemia , Liver/pathology , Male , Rats , Rats, Sprague-Dawley , Reperfusion Injury/pathology , Time Factors , Triglycerides/blood , Tumor Necrosis Factor-alpha/metabolism
8.
Ultrasound Med Biol ; 23(9): 1413-20, 1997.
Article in English | MEDLINE | ID: mdl-9428140

ABSTRACT

Liver hemorrhage, the major cause of death in hepatic trauma, is notoriously difficult to control. We report on the use of high-intensity focused ultrasound (HIFU) to arrest the bleeding from incisions made in rabbit livers. A HIFU transducer, with a spherically curved aperture of 6.34 cm2 area, a focal length of 4 cm and a frequency of 3.3 MHz was used. In approximately 94% of the incisions, the hemorrhage was reduced to a slow oozing of blood in less than 2 min. The maximum temperature of liver tissue around the incision area, during HIFU application, was measured to be 86 degrees C. The mechanism of hemostasis, confirmed by histological examination, appears to be coagulative necrosis of a volume of liver tissue around the incision. We believe that acoustic hemostasis, with the unique characteristic of "volume cauterization," offers a novel method for the management of liver hemorrhage and, thus, has major clinical implications.


Subject(s)
Hemorrhage/therapy , Hemostatic Techniques , Liver Diseases/therapy , Ultrasonic Therapy/methods , Animals , Bile Ducts/pathology , Body Temperature , Disease Models, Animal , Hemorrhage/pathology , Hemorrhage/physiopathology , Hepatic Artery/pathology , Hepatic Veins/pathology , Hot Temperature , Liver/injuries , Liver Diseases/pathology , Liver Diseases/physiopathology , Necrosis , Rabbits , Treatment Outcome
10.
Anesth Analg ; 70(1): 16-21, 1990 Jan.
Article in English | MEDLINE | ID: mdl-2297100

ABSTRACT

The purpose of this study was to characterize the pharmacodynamics and pharmacokinetics of three concentrations of the new long-acting amide local anesthetic, ropivacaine, given epidurally in 15 physical status ASA I or II patients for elective lower-extremity orthopedic procedures using a nonrandomized open-label design. Three groups of five patients each received either 0.5%, 0.75%, or 1.0% ropivacaine. Upper and lower levels of analgesia to pinprick were determined at frequent intervals until normal sensation had completely returned. Motor blockade was assessed by use of a modified Bromage scale after each determination of level of analgesia. Fifteen venous blood samples were collected over 12 h after ropivacaine injection. Pharmacokinetic parameters were derived using serum concentration-time data. No significant differences were found between the three groups in terms of onset or recovery of motor and sensory blockade. Median maximum thoracic levels of analgesia achieved were 8, 6, and 5 for the 0.5%, 0.75%, and 1.0% groups, respectively, and occurred at 29 +/- 11, 37 +/- 21, and 30 +/- 9 min. Respective times to two-segment regression were 2.8 +/- 1.0, 3.0 +/- 0.5, and 2.9 +/- 0.6 h. Total durations of sensory blockade were 5.4 +/- 0.7, 6.5 +/- 0.4, and 6.8 +/- 0.8 h, respectively. No statistically significant differences were noted between the three groups in terms of clearance (CL). The mean residence time (MRT) was significantly longer for the 0.5% group when compared with the 1% group. The peak concentration (Cmax) for the 0.5% group was found to be significantly lower than for either the 0.75% or 1% groups.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Amides/pharmacology , Anesthesia, Epidural , Anesthetics, Local/pharmacology , Adult , Amides/pharmacokinetics , Anesthetics, Local/pharmacokinetics , Female , Humans , Male , Metabolic Clearance Rate , Middle Aged , Ropivacaine
11.
Endocrinology ; 124(4): 1849-56, 1989 Apr.
Article in English | MEDLINE | ID: mdl-2466638

ABSTRACT

Calcitonin gene-related peptide (CGRP), a 37-amino acid peptide, has been shown to be a potent inhibitor of pancreatic exocrine secretion when administered exogenously The present study was performed to determine if this inhibitory effect is due to the direct actions of exogenous CGRP on the exocrine pancreas or to the effects of another inhibitor released by CGRP. To this end, we first confirmed the inhibitory effects of the peptide on exocrine function by infusing the peptide into conscious rats previously prepared with bile-pancreatic fistulas and measuring cholecystokinin-stimulated amylase and protein outputs. CGRP produced a dose-dependent inhibition of both protein and amylase outputs in vivo. In marked contrast, CGRP in vitro had no direct inhibitory effect on amylase output from either the isolated buffer-perfused pancreas or dispersed acinar cells. Thus, the inhibitory effects of exogenous CGRP on pancreatic exocrine function appear to be indirect. In an attempt to determine the mediator of the inhibitory effects of CGRP, we assessed the ability of similar doses of CGRP to stimulate the release of a potential endogenous inhibitor of pancreatic exocrine function, circulating somatostatin. In conscious rats, iv CGRP dose-dependently increased circulating plasma somatostatin-like immunoreactivity from 35 +/- 5 to 86 +/- 7 fmol/ml. To determine if these increments in circulating somatostatin were sufficient to impair exocrine function, the isolated pancreas was exposed in vitro to a similar concentration of somatostatin. Somatostatin perfusion resulted in a significant inhibition of pancreatic amylase output (73%). Overall, these results support the hypothesis that 1) the inhibitory effect of exogenous CGRP on pancreatic exocrine function is indirect; 2) exogenous CGRP stimulates the release of endogenous somatostatin into the systemic circulation; and 3) the concentration of circulating somatostatin is sufficient to mediate the effect of exogenous CGRP on the exocrine pancreas.


Subject(s)
Neuropeptides/pharmacology , Pancreas/metabolism , Somatostatin/pharmacology , Amylases/metabolism , Animals , Calcitonin Gene-Related Peptide , Cell Separation , Dose-Response Relationship, Drug , Male , Pancreas/cytology , Pancreas/drug effects , Perfusion , Proteins/metabolism , Rats , Rats, Inbred Strains , Sincalide/pharmacology , Somatostatin/blood , Somatostatin/immunology
12.
J Anim Sci ; 66(2): 361-71, 1988 Feb.
Article in English | MEDLINE | ID: mdl-2897353

ABSTRACT

Male mice selected for rapid 3 to 6 wk postweaning gain (M16) and unselected controls (ICR) were ad libitum fed a stock diet containing 0, 50 or 200 ppm cimaterol, a beta-agonist, from 4 to 7 or 4 to 10 wk of age. Mortality rate was higher in M16 than in ICR mice fed cimaterol (12.5 vs 1.3%; P less than .01). No mortalities occurred in either line fed the control diet. Line M16 exceeded (P less than .01) ICR in growth rate, feed intake, feed efficiency and lean index. Line X cimaterol level interactions (P less than .01) were found for the first three of these traits, although cimaterol level did not change line ranking. Epididymal fat as a percentage of empty body weight decreased at a faster rate in M16 than in ICR as cimaterol level increased. At 0 and 50 ppm, M16 exceeded ICR (P less than .05), but at 200 ppm there was no line difference (P greater than .05). Line M16 exceeded (P less than .05) ICR in blood glucose (5%), nonesterified fatty acids (4%) and lactate at 7 wk (9%), but lactate was higher in ICR at 10 wk (13%). Lines were not different in blood urea-N. Compared to zero cimaterol level, at 50 and 220 ppm glucose decreased (14% and 23%; P less than .05), nonesterified fatty acids decreased (3% and 29%; P less than .05), lactate increased (9% and 11%; P less than .05) and blood urea-N increased (3% and 16%; P less than .05). There were no line X cimaterol level interactions for blood metabolites. Differences in mortality rate, growth, feed consumption, feed efficiency and epididymal fat pad percentage between the high-growth and control lines in response to cimaterol may reflect genetic differences in mechanisms of metabolic regulation.


Subject(s)
Adrenergic beta-Agonists/pharmacology , Body Weight/drug effects , Ethanolamines/pharmacology , Mice, Inbred Strains/genetics , Selection, Genetic , Adrenergic beta-Agonists/administration & dosage , Animals , Body Composition/drug effects , Ethanolamines/administration & dosage , Male , Mice , Mice, Inbred ICR , Mice, Inbred Strains/growth & development , Models, Biological , Organ Size/drug effects
13.
J Toxicol Environ Health ; 24(4): 499-513, 1988.
Article in English | MEDLINE | ID: mdl-3411634

ABSTRACT

A group of 36 aryl azo dyes were examined for their ability to be reduced by rat liver microsomal azoreductase. This group of azo dyes featured a variety of substituents, including sulfonic acid, phenol, nitro, amide, and methyl functionalities on phenyl, alpha-naphthyl, and beta-naphthyl rings. Reduction rates for each dye were obtained using a spectrophotometric method and anaerobic incubation conditions. These rates ranged from 0 to 7.35 nmol dye reduced/min.mg protein. The reduction rates and dye structures provided the data for a CASE-SAR (computer automated structure evaluation-structure-activity relationship) fragment analysis, and three major structure fragments associated with the ability of this group of azo dyes to be reduced were identified. The three CASE fragments correctly label 92% of the azo dye structures as active or inactive and may be useful in future predictions of the ability of azo dyes to undergo reduction by rat liver azoreductase.


Subject(s)
Azo Compounds/metabolism , Coloring Agents/metabolism , Microsomes, Liver/metabolism , NADH, NADPH Oxidoreductases/metabolism , Animals , Male , Nitroreductases , Oxidation-Reduction , Rats , Structure-Activity Relationship
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