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P Duffy

Publications and source records attributed to P Duffy.

At least 55 records · Page 3Linked to original sources
PubMed1997

Dopamine regulation of extracellular glutamate in the nucleus accumbens.

The capacity of dopamine to alter extracellular glutamate in the nucleus accumbens was examined by passing 1, 10 and 100 microM of amphetamine, the D(2/3) agonist, quinpirole, or the D1 agonist, SKF-82958 through a microdialysis probe. It was found that amphetamine and quinpirole produced a dose-dependent reduction in the basal levels of extracellular glutamate, while SKF-82958 was without significant effect. The capacity of the D1 antagonist, SCH-23390 (1.0 mg/kg, i.p.) or the D2 antagonist, sulpiride (10 mg/kg, i.p.) to block the reduction in extracellular glutamate by amphetamine (100 microM) was examined. Both SCH-23390 and sulpiride prevented the reduction in extracellular glutamate by amphetamine. The data indicate that, similar to the striatum, glutamate release in the nucleus accumbens is modulated by presynaptic dopamine receptors.

Amphetamine↗
PubMed1997

Superovulation in cattle: effect of FSH type and method of administration on follicular growth, ovulatory response and endocrine patterns.

Although different FSH preparations and injection regimens are used to superovulate cattle, the optimum treatment regimen and blood concentrations of FSH to induce effective superovulatory responses are currently not known. The current objective was to evaluate the pattern of follicular growth, oestradiol-17 beta(E2) concentrations and yield of embryos in heifers following superovulation with two different pFSH preparations reportedly differing in LH content. In experiment 1, 90 synchronised heifers were superovulated at mid-cycle using a 2 x 2 factorial design comparing Folltropin (Vetrepharm; low LH) with Pluset (Serovet; FSH:LH ratio 1:1) administered either as a single or multiple (8 for Folltropin, MF and 10 for Pluset, MP) injections. Animals were inseminated during oestrus which was induced with prostaglandin F2 alpha analogue and embryos were recovered 7 days later. Overall, Pluset treatments compared with Folltropin resulted in more ovulations and unfertilized or degenerate embryos (P < 0.05). Multiple injections resulted in more (P < 0.05) freezable (MF = 55 +/- 1.2; MP = 3.8 +/- 1.0) and transferable embryos (MF = 2.68 +/- 0.9; MP = 2.71 +/- 0.9) than single injections (SF = 2.2 +/- 0.5 and 1.0 +/- 0.3 respectively; SP = 2.6 +/- 0.8 and 1.3 +/- 0.4 respectively); there was also a higher (P < 0.05) percentage embryo recovery rate. In two subsequent experiments, animals (n = 17) were superovulated with either single or multiple injections of Folltropin or Pluset as described and blood samples were collected and analysed for E2 concentrations. Ovarian scanning was carried out until 72 h after the first FSH injection, to count medium (5-9 mm) and large (> or = 10 mm) follicles. Heifers treated with SP had higher E2 concentrations in comparison with heifers treated with SF at 18, 36-48 and 84-96 h after the FSH injection. There were no differences in E2 concentrations in heifers treated with MF or MP treatments. Heifers treated with SP had greater numbers of follicles compared to SF treated heifers (21.0 +/- 3.1 vs 13.9 +/- 2.2; P = 0.089) on the third day after FSH injection. There were no differences between the numbers of medium and large follicles in heifers treated with MF or MP at any time throughout the experimental period. These data indicate that a single injection of Folltropin or Pluset can result in multiple ovulations and that the E2 profiles are different following single injections of either Folltropin or Pluset.

Animals↗
PubMed1997

Congenital cutis laxa and lysyl oxidase deficiency.

We report two phenotypically similar patients with primary cutis laxa associated with deficiency of lysyl oxidase, an extracellular copper enzyme the gene for which is located on chromosome 5. Previous reports of this condition have had characteristic occipital projections, abnormality of copper metabolism and X-linked inheritance. The two reported patients have no occipital projections, normal copper metabolism, Wormian bones, and a pattern of inheritance consistent with the autosomal recessive inheritance of the lysyl oxidase gene.

Child↗
PubMed1997

Genetic effects on variation in red-blood-cell folate in adults: implications for the familial aggregation of neural tube defects.

Recent studies have implicated folic acid as an important determinant of normal human growth, development, and function. Insufficient folate levels appear to be a risk factor for neural tube defects (NTD), as well as for several chronic diseases of adulthood. However, relatively little is known about the factors that influence folate status in the general population. To estimate the relative contribution of genetic and nongenetic factors to variation in folate, we have evaluated red blood cell (RBC) folate levels in 440 pairs of MZ twins and in 331 pairs of DZ twins. The data were best described by a model in which 46% of the variance in RBC folate was attributable to additive genetic effects, 16% of the variance was due to measured phenotypic covariates, and 38% of the variance was due to random environmental effects. Moreover, the correlations for RBC folate in MZ co-twins (r = .46) and in repeat measures from the same individual (r = .51) were very similar, indicating that virtually all repeatable variation in RBC folate is attributable to genetic factors. On the basis of these results, it would seem reasonable to initiate a search for the specific genes that influence RBC folate levels in the general population. Such genes ultimately may be used to identify individuals at increased risk for NTD and other folate-related diseases.

Adult↗
PubMed1996

Repeated cocaine augments excitatory amino acid transmission in the nucleus accumbens only in rats having developed behavioral sensitization.

Rats were pretreated with daily cocaine or saline injections for 1 week. The rats treated with daily cocaine were separated into two groups: a sensitized group of animals demonstrating > 20% increase in motor activity on the last injection compared with the first injection of daily cocaine, and a nonsensitized group showing < 20% elevation. At 2-3 weeks after the last daily injection, four experiments were performed to assess changes in excitatory amino acid (EAA) transmission in the nucleus accumbens produced by repeated cocaine administration. (1) Rats were challenged with a microinjection of AMPA into the shell or core of the nucleus accumbens. The sensitized rats demonstrated greater motor activity than did the saline-pretreated or nonsensitized animals after AMPA injection into either subnucleus. (2) It was shown that the behavioral distinction between sensitized, nonsensitized, and control rats in behavioral responsiveness to AMPA was not mediated by differences in AMPA-induced dopamine release. (3) The extracellular content of glutamate was measured after a cocaine challenge given at 21 d of withdrawal. Cocaine elevated the levels of glutamate in the core of sensitized rats, but not of nonsensitized or control rats. (4) Microinjection of the non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione into the core abolished the augmented motor response to a cocaine challenge in sensitized rats, but was without effect on cocaine-induced motor activity in nonsensitized animals. These results indicate that repeated cocaine administration increases EAA transmission in the nucleus accumbens only in rats that develop behavioral sensitization to cocaine.

Animals↗
PubMed1996

The mediodorsal nucleus of the thalamus in rats--II. Behavioral and neurochemical effects of GABA agonists.

The aim of this study was to determine how GABA receptors in the mediodorsal nucleus of the thalamus in rats might contribute to the regulation of locomotor behavior. Microinjections of the GABAB and GABAA agonists, baclofen and muscimol, into the mediodorsal nucleus produced dose-dependent increases in locomotion that were blocked by co-administration of the GABAB antagonist, 2-hydroxysaclofen. Microinjection of baclofen along the midline, lateral into the ventrolateral thalamus or into the lateral ventricles produced significantly smaller dose-dependent increases in locomotion, indicating that the anatomical locus for baclofen-induced locomotion resides in the mediodorsal nucleus. The motor response elicited by microinjected baclofen was associated with a reduction in dopamine metabolism in the prefrontal cortex and an increase in metabolism in the core of the nucleus accumbens, but not in the accumbal shell or the dorsolateral striatum. These results suggest that GABAergic afferents to the mediodorsal nucleus may oppose a tonic inhibitory tone on locomotor activity. The data also suggest that the motor response produced by baclofen in the mediodorsal thalamus may arise by inhibiting the projections to the prefrontal cortex which modulate mesocorticolimbic dopamine transmission.

Animals↗
PubMed1995

Selective activation of dopamine transmission in the shell of the nucleus accumbens by stress.

A microdialysis probe was placed in either the shell or core compartment of the nucleus accumbens and rats were exposed to mild footshock. Extracellular dopamine levels in the shell of the nucleus accumbens were elevated during the 20-min collection period immediately after discontinuing footshock. In contrast, the levels of dopamine remained unaltered in the core of the nucleus accumbens.

Animals↗
PubMed1995

Sensitization to cocaine and dopamine autoreceptor subsensitivity in the nucleus accumbens.

It has been suggested that dopamine autoreceptor subsensitivity may play a role in cocaine-induced behavioral sensitization. In order to evaluate this hypothesis, we administered cocaine to rats daily (15 mg/kg ip x 2 days, 30 mg/kg ip x 5 days) and then monitored nucleus accumbens dopamine during the local administration (through the dialysis probe) of the D2/D3 agonist, quinpirole (0, 0.1, 1, and 10 microM). Our results indicate that, relative to saline-pretreated control animals, repeated cocaine administration impaired the ability of quinpirole to decrease extracellular dopamine 1-2 days after the last drug injection. However, quinpirole was equipotent at reducing accumbal dopamine in cocaine- and saline-treated animals following a 21-22 day withdrawal period. These results demonstrate that repeated cocaine produces a short duration functional tolerance in the capacity of autoreceptor stimulation to inhibit accumbal dopamine release.

Animals↗
PubMed1995

The correlation between follicular measurements, oocyte morphology, and fertilization rates in an in vitro fertilization program.

OBJECTIVE: To explore the relationship between follicle size and the morphology of the oocyte-cumulus-corona complex with fertilization rates in stimulated cycles of IVF. DESIGN: Retrospective comparison of measurements and observations of 2,429 oocytes from 215 patients undergoing 324 stimulated IVF cycles. SETTING: A large hospital-based IVF program. MAIN OUTCOME MEASURES: Individual follicles were measured by ultrasound before transvaginal aspiration and the size was recorded. The oocyte-cumulus-corona complex from each follicle was examined and classified. The oocytes were checked for evidence of fertilization 17 to 22 hours after insemination. RESULTS: The fertilization rate of all oocytes regardless of morphological type revealed a positive linear correlation with increasing follicle diameter. The fertilization rates of type I oocytes was marginally higher than type II oocytes, controlling for follicle diameter; however, this difference did not achieve statistical significance. Oocytes from follicles with a mean diameter > or = 16 mm had significantly higher fertilization rates than did oocytes from follicles with a mean diameter < or = 14 mm. CONCLUSIONS: Follicle size is a better predictor of fertilization than is morphological characterization of the oocyte-cumulus-corona complex in IVF.

Female↗
PubMed1995

The use of the hCG stimulation test in the endocrine evaluation of cryptorchidism.

OBJECTIVE: To review retrospectively the value of the human chorionic gonadotrophin (hCG) test in the evaluation of prepubertal boys with bilateral impalpable testes. SUBJECTS AND METHODS: The study comprised 31 boys investigated between 1974 and 1990 at the Hospital for Sick Children, London. All boys had an hCG test consisting of three intramuscular injections of hCG on successive days at a daily dose dependent on their age (< 1 year old, 500 units; 1-10 years, 1000 units; > 10 years, 1500 units). Blood samples were taken before the first dose and 24 h after the last dose and the level of plasma testosterone assessed and expressed as a pre/post ratio. RESULTS: Eight boys had no response to hCG, due to anorchia. One boy had no response to hCG but had bilateral atrophic intra-abdominal testes. Twenty-two boys responded to hCG and had testes whose size was related to the degree of testosterone elevation after this stimulatory test. The hCG test therefore had a positive predictive value of 89% and a negative predictive value of 100%. There was a quantitative difference in testosterone response between 14 boys who had bilateral intra-abdominal testes of 'normal' volume (median pre/post ratio, 11.4) and nine boys who had an otherwise reduced volume of testes (dysplastic or unilateral intra-abdominal) (median pre/post ratio of 4; P = 0.02). CONCLUSION: The hCG test is a valid indicator of the presence of functioning testicular tissue. It is predictive of anorchia and a good response to hCG suggests the presence of testes sufficiently large for orchidopexy.

Child↗
PubMed1995

D1 receptors modulate glutamate transmission in the ventral tegmental area.

Perfusion of the D1 agonist, SKF-82958, through a microdialysis probe implanted in the ventral tegmental area produced a dose-dependent increase in extracellular glutamate and GABA. The increase in extracellular glutamate occurred at approximately 30x lower dose than the elevation in GABA. The increase in extracellular glutamate by SKF-82958 was blocked by coperfusion of the D1 antagonist, SCH-23390, and was not mimicked by perfusion of the D2/3 agonist, quinpirole, into the ventral tegmental area. In contrast, the elevation in extracellular GABA was insensitive to blockade by SCH-23390. Systemic administration of cocaine (15 mg/kg, i.p.) produced a rapid elevation in extracellular glutamate lasting for 20 min that was prevented by pretreating the ventral tegmental area with SCH-23390. In contrast, acute cocaine produced a reduction in extracellular GABA content in the ventral tegmental area that was not affected by SCH-23390. These data indicate that the stimulation of D1 receptors in the ventral tegmental area increases the release of glutamate and that increasing extracellular levels of somatodendritic dopamine by systemic cocaine can mimic this effect.

Animals↗
PubMed1994

Behavioral and neurochemical sensitization following cocaine self-administration.

To determine if behavioral and neurochemical sensitization results from cocaine self-administration, rats were trained to self-administer cocaine for 20 consecutive days (26.5 +/- 2.6 mg/kg, IV/day). At 24 h or 21 days after discontinuing cocaine self-administration or yoked saline control, rats were administered an acute injection of saline IP, followed 60 min later by cocaine (15 mg/kg IP). Cocaine-induced changes in motor activity were monitored with a photocell apparatus and alterations in extracellular dopamine in the ventral striatum were measured with microdialysis. There was no difference between treatment groups in the basal level of extracellular dopamine as determined by in vitro calibration. Neither the motor stimulant response nor the increase in extracellular dopamine following an acute cocaine challenge given after 24 h of withdrawal was different between rats which self-administered cocaine and yoked saline controls. However, when the cocaine challenge was given 21 days after discontinuing cocaine self-administration both the motor response and extracellular dopamine content in the ventral straitum were significantly augmented in rats that self-administered cocaine. While no correlation was observed between the average amount of cocaine self-administered each day and the cocaine-induced alterations in extracellular dopamine at either 24 h or 21 days of withdrawl, a significant positive correlation was measured between the increase in photocell counts and the average daily cocaine administration at 21 days of withdrawl. These data show that cocaine self-administration produces an augmentation in the acute behavioral and neurochemical response to a cocaine challenge that resembles the sensitization previously demonstrated with repeated noncontingent administration.

Animals↗
PubMed1994

Methylenedioxymethamphetamine depresses glutamate-evoked neuronal firing and increases extracellular levels of dopamine and serotonin in the nucleus accumbens in vivo.

The nucleus accumbens has been implicated as an important site for the actions of many drugs that are used recreationally. This study examined the effects of methylenedioxymethamphetamine (MDMA), a euphoric and hallucinogenic drug, on glutamate-evoked neuronal firing and on extracellular levels of dopamine and serotonin in the nucleus accumbens of the rat. Microiontophoretic application of MDMA inhibited glutamate-evoked firing of most of the nucleus accumbens cells that were tested (83 of 86), as did microiontophoretic application of dopamine and serotonin. MDMA-induced inhibition of glutamate-evoked firing was partially blocked by the dopamine antagonist SCH39166 and was attenuated by combined pretreatment with inhibitors of both serotonin and catecholamine synthesis, p-chlorophenylalanine and alpha-methyl-p-tyrosine. MDMA applied directly into the nucleus accumbens and adjacent regions of the ventral striatum through a dialysis probe increased extracellular levels of both dopamine and serotonin. These results indicate that MDMA has inhibitory effects on glutamate-evoked neuronal firing in the nucleus accumbens and suggest that the inhibition is mediated by increased extracellular dopamine and serotonin. Furthermore, these results permit MDMA to be added to the extensive list of abused drugs that have been demonstrated to elevate extracellular levels of dopamine and serotonin in the nucleus accumbens.

Animals↗
PubMed1994

Quantification and localization of cortical granules during oogenesis in the mouse.

Although the important subplasmalemmal localization of cortical granules (CG) has been documented, little is known about the timing and mechanism of granule translocation to the oocyte cortex. A fluorescent CG probe, confocal microscopy, and image analysis were used to obtain kinetic, spatial, and temporal information about CG migration during mouse oogenesis. The mean CG density in the cortex increased exponentially, from 3 to 14 CG/100 microns 2, during oocyte growth from 40-50 microns to 70-80 microns in diameter, respectively. Full-grown, > or = 80-microns, germinal vesicle-intact oocytes had a density of 30-35 CG/100 microns 2. During growth from 40-50 microns to > or = 80 microns, the mean total number of CG in the cortex per oocyte increased from < 500 to > 6000. When analyzed in terms of the stage of germinal vesicle chromatin organization, the mean CG density increased from 3 to 21 CG/100 microns 2 from stage I to early stage IV, respectively. In 50-60-microns oocytes, there was a crescent-shaped area of perinuclear staining containing both granules and Golgi apparatus-like structures, which were also more sparsely distributed in the subcortical cytoplasm. It is likely that these were sites of CG production from which translocation takes place; they were not observed in ovulated metaphase II eggs. This study demonstrates that CG number in the cortex increases continually during mouse oocyte growth (in contrast to that in several other species), that there is a greater than twofold increase in CG number during the final phase of growth, and that subcortical production ceases after ovulation.

Animals↗
PubMed1994

Immunological detection of cardiac glycosides in plants.

Australian native and introduced plants were examined, using digoxin immunoassays, to detect the presence of cross-reacting cardiac glycosides. These compounds were found in 27 species from 20 genera. The assay technique can also be used on serum samples to confirm cardiac glycoside ingestion.

Animals↗