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P Duffy

Publications and source records attributed to P Duffy.

At least 91 records · Page 5Linked to original sources

Effect of acute and daily cocaine treatment on extracellular dopamine in the nucleus accumbens.

The behavioral stimulant effect of peripheral cocaine injection into rats is augmented following daily administration. In vivo dialysis in the nucleus accumbens of conscious rats was used to determine if the increased behavioral response following daily cocaine administration is associated with an increase in extracellular dopamine concentration. Acute injection of cocaine (15 mg/kg, ip) produced an elevation in extracellular dopamine concentration in the nucleus accumbens. Following daily pretreatment with cocaine (15 mg/kg, ip X 4 days), a subsequent acute injection of cocaine (15 mg/kg, ip) significantly elevated the extracellular dopamine levels compared to that produced by a single acute injection. Although the levels of extracellular dopamine metabolites was significantly lowered by both acute cocaine and daily cocaine, no difference between these two groups of animals was measured. The increase in extracellular dopamine following a single acute injection of cocaine was not correlated to the motor stimulant response. However, after daily pretreatment with cocaine the motor stimulant response to acute cocaine was positively correlated with the increased extracellular concentration of dopamine in the nucleus accumbens. These data demonstrate that enhanced dopamine release into the nucleus accumbens may mediate the behavioral sensitization produced by daily injections of cocaine, but that other neural systems are influential in mediating the acute motor stimulant effect of cocaine.

3,4-Dihydroxyphenylacetic Acid↗

Superovulation in heifers given FSH initiated either at day 2 or day 10 of the estrous cycle.

The aim of this study was to determine if initiation of superovulation in heifers during the time of development of the first dominant follicle (Days 2 to 6) would give equivalent ovulation and embryo production rates as treatment initiated at mid-cycle. Estrus was synchronized in 60 beef heifers using luprostiol (PG) and they were randomly allocated to treatment with 4.5, 3.5, 2.5 and 1.5 mg of porcine follicle stimulating hormone (FSH) administered twice daily, either on Days 2, 4, 5 and 6 (Day-2 group), respectively, or with similar doses at four consecutive days during mid-cycle (Day-10 group, initiation on Day 9 to 11). All heifers received 500 mug cloprostenol at the fifth FSH injection and 250 mug at the sixth injection. Blood samples for progesterone determination were collected at the time of FSH injections. Heifers were slaughtered 7 d post estrus, and the number of ovulations and large follicles (>/=10mm) were determined on visual inspection of the ovary. Following flushing of the uterine horns the quality of embryos and the fertilization rate were determined. Significant differences between treatments were determined using a two-sided t-test, and frequency distributions were compared using Chi-square tests. The mean number (+/-SEM) of ovulations for heifers in the Day-10 group was 12.9+/-1.0, and 8.5+/-0.9 embryos were recovered. Both the number of ovulations (6.7+/-0.8) and embryos recovered (4.1+/-0.6) were lower (P=0.0001) in heifers in the Day-2 group. Following grading based on a morphological basis, a higher number (P=0.002) of embryos was categorized as Grades 1 and 2 (4.1+/-0.6) and Grade 3 (2.1+/-0.4) in Day-10 heifers than in the Day-2 group (Grade 1 and 2, 1.9+/-0.3; Grade 3, 0.7+/-0.2). The number of Grade 4 and 5 embryos (Day 10, 1.6+/-0.2; Day 2, 1.4+/-0.2) and the number of unfertilized ova (Day 10, 0.7+/-0.4; Day 2, 0.2+/-0.1) did not differ between treatments. Progesterone concentrations were lower (P=0.0001) in Day-2 heifers at FSH treatment prior to prostaglandin, and the decline was more rapid following prostaglandin injection at Day 5 (P=0.02). Results of this study indicate that the number of ovulations and embryos recovered was lower in heifers when FSH treatment was initiated on Day 2 compared with Day 10 of the estrous cycle.

Journal Article↗

Colour Doppler ultrasound in deep venous thrombosis: a comparison with venography.

Colour Doppler ultrasound is a new technical development allowing simultaneous grey scale imaging and a dynamic colour flow vascular image. To date, many real time ultrasonic studies have been assessed in the diagnosis of lower limb venous thrombosis and have been shown to be accurate in the femoral and popliteal segments. A double blind prospective study comparing colour Doppler with contrast venography in the diagnosis of lower limb thrombosis was performed in a group of 40 patients. Of the study group, 26 venograms were negative and 27 ultrasound examinations were negative. Of the 14 positive venograms there was one false negative colour doppler scan which missed a calf and lower popliteal thrombosis. Two cases of isolated calf vein thrombosis were successfully detected by colour Doppler. Overall, the sensitivity and specificity for detection of lower limb venous thrombosis, including calf vein assessment, were 93% and 100% respectively. Colour Doppler is easy to perform; the average scanning time being 15 minutes for complete assessment of a unilateral lower limb venous system. Spontaneous flow is evident in the femoropopliteal segment, whilst proximal calf vein flow can only be appreciated with the aid of distal compression. Eccentric thrombus and partially recanalized thrombus can be shown. Although the number of isolated calf vein thromboses was small, early experience suggests colour Doppler may be useful in the assessment of proximal calf vein patency.

Adult↗

Changes in the distribution of mouse oocyte cortical granules and ability to undergo the cortical reaction during gonadotropin-stimulated meiotic maturation and aging in vivo.

Mouse oocyte cortical granule (CG) activation and distribution were investigated during in vivo meiotic maturation to determine the onset of competence to undergo the cortical reaction, which is considered responsible for the block to polyspermy. In the present study, the resumption of oocyte maturation was stimulated by hCG administration. Competence to undergo the cortical reaction (assessed with calcium ionophore A23187) was undetectable (0% loss) in germinal vesicle-stage oocytes 0.5 h after hCG administration. When germinal vesicle breakdown and metaphase I had taken place (3 and 7 h post hCG, respectively), approximately 30% CG loss was observed. Maximal (A23187-inducible) levels of CG loss, 67% and 72%, were present at 10 and 13 h, respectively, during metaphase II. Cortical granule distribution changed dramatically during metaphase I, polar body formation, metaphase II, and post-ovulatory aging in vivo. A stable metaphase II distribution was present from 13 to 18 h. After 24 and 32 h, 28% and 83% of the eggs, respectively, exhibited major alterations in the cortical distribution of CGs, some of which did not appear to be susceptible to release by A23187. These data support the hypothesis that just before ovulation the egg cortex completes the development of its normal structure and physiological competence, which are maintained for only a brief period of time afterward. The implications are discussed for normal fertilization and polyspermy in mammals, including humans.

Aging↗

Effect of acute and daily neurotensin and enkephalin treatments on extracellular dopamine in the nucleus accumbens.

The injection of neurotensin or the enkephalin analog Tyr-D-Ala-Gly-MePhe-Gly(ol) (DAMGO) into the A10 region of rats produces a motor stimulant effect that is associated with an increase in the postmortem levels of dopamine metabolites in the nucleus accumbens. These behavioral and neurochemical effects are augmented following daily administration. In vivo dialysis in the nucleus accumbens of conscious rats was used to determine if the acute and augmented behavioral responses following neurotensin or DAMGO administration are associated with an increase in extracellular dopamine concentrations. The acute injection of DAMGO produced a dose-dependent (0.03-3.3 nmol) elevation in extracellular dopamine and its metabolites in the nucleus accumbens. Neurotensin also produced a dose-related (0.1-3.3 nmol) increase in dopamine and its metabolites. The elevation in extracellular dopamine produced by DAMGO, but not by neurotensin, was positively correlated with the increase in motor activity. Following daily treatment of either neurotensin (1.0 nmol X 4 d) or DAMGO (0.03 nmol X 4 d), a significant elevation in extracellular dopamine levels occurred in the nucleus accumbens compared to an acute injection. The time course of the change in extracellular dopamine after daily injections was similar to the time course of the behavioral stimulation for both compounds. These data demonstrate that enhanced dopamine release in the nucleus accumbens mediates the acute behavioral effect of DAMGO but does not entirely explain the motor effects of neurotensin. However, enhanced dopamine release may mediate the behavioral sensitization produced by daily injection of both peptides into the A10 region.

3,4-Dihydroxyphenylacetic Acid↗

Modulation of A10 dopamine neurons by gamma-aminobutyric acid agonists.

Microinjection of the gamma-aminobutyric acidA agonist, muscimol, into the A10 region of the rat produced a dose-dependent increase in motor activity. This effect was antagonized by intra-A10 administration of the gamma-aminobutyric acidA antagonist, bicuculline, and by peripheral administration of haloperidol, and was associated with an increase in extracellular levels of dopamine metabolites in the nucleus accumbens. Although microinjection of the gamma-aminobutyric acidB agonist, baclofen, into the A10 region did not alter motor activity, it abolished the capacity of intra-A10 injection of mu opioid agonist, Tyr-D-Ala-Gly-MePhe-Gly(ol), or muscimol to increase motor activity. Baclofen also prevented the motor stimulant response to peripheral injection of cocaine or amphetamine, but was ineffective in blocking caffeine-induced behavioral activity. Pretreatment with baclofen prevented the capacity of a mu opioid agonist to elevate dopamine metabolite levels in the nucleus accumbens and prefrontal cortex in postmortem tissue. Baclofen also prevented the elevation of extracellular dopamine content in the nucleus accumbens produced by injection of a mu opioid agonist into the A10 region, as measured in the conscious rat with in vivo dialysis. Finally, when dopamine metabolite levels were elevated in the prefrontal cortex by mild footshock, it was shown that pretreatment with baclofen in the A10 region abolished this response. These data support electrophysiological studies suggesting that activation of gamma-aminobutyric acidB receptors on dopamine perikarya inhibits dopaminergic activity, while activation of gamma-aminobutyric acidA receptors results in an indirect disinhibition of dopaminergic function.

Animals↗

A comparison of 5-hydroxytryptophan effects on rat lumbar spinal cord serotonin release and monosynaptic response amplitude.

The physiological effects of injections of the serotonin precursor, 5-hydroxytryptophan (5-HTP) are thought to result from increased serotonin (5-HT) release, although release has not been directly measured in vivo. This study compared the effects of 5-HTP on rat lumbar spinal cord monosynaptic response (MSR) amplitude and on 5-HT release into lumbar extracellular fluid as measured by in vivo dialysis. 5-HTP significantly increased the amplitude of the MSR and significantly increased the amount of 5-HT in dialysate samples suggesting that 5-HTP enhances the lumbar MSR amplitude by increasing 5-HT release.

5-Hydroxytryptophan↗

Similar effects of daily cocaine and stress on mesocorticolimbic dopamine neurotransmission in the rat.

Daily exposure to cocaine or stress has been shown to enhance the motor stimulant effect of a subsequent injection of acute cocaine. Considering that both cocaine and stress enhance dopamine neurotransmission in the central nervous system, it was of interest to determine the effects of daily cocaine and stress on the capacity of acute stress to alter dopamine neurotransmission. Rats were injected with cocaine (15 mg/kg, ip) for 3 days or exposed to daily 20 min of footshock stress (0.3 mA/200 msec/sec) for 10 days. Ten to 14 days later, the rats were exposed to acute footshock or sham shock for 0, 5, 10, or 20 min, and the concentration of dopamine and its metabolites was measured in the A10 and A9 dopamine regions, nucleus accumbens, striatum, and prefrontal cortex. It was found that the daily treatments resulted in an enhancement of dopamine metabolism in the prefrontal cortex and nucleus accumbens in response to acute footshock. In contrast, dopamine metabolism was diminished in the A10 region, and no change was measured in the striatum or A9 region. It is proposed that pretreatment with cocaine or stress alters the response of the mesocorticolimbic dopamine neurons to subsequent stress, so that axonal dopamine neurotransmission is enhanced in the terminal fields and somatodendritic dopamine neurotransmission is diminished. Furthermore, the long-lasting influence of daily cocaine and stress on mesocorticolimbic dopamine responsiveness to subsequent stressful experiences may be relevant in the etiology of psychostimulant-induced psychosis.

3,4-Dihydroxyphenylacetic Acid↗

Effect of long-term caloric restriction on brain monoamines in aging male and female Fischer 344 rats.

The present study examines the changes in central monoamines and their metabolites in aged male and female rats after long-term caloric restriction. Fischer 344 rats of both sexes (n = 5-10/group) were maintained on one of two dietary regimens: ad libitum NIH 31 diet or 60% by weight of the ad lib. intake (restricted), supplemented with vitamins and minerals. Animals received these diets from the age of 14 weeks until killed at 22.25 months of age. Caudate nucleus (CN), hypothalamus (HYPO), olfactory bulb (OB) and nucleus accumbens (NA) were assayed for content of norepinephrine (NE), dopamine (DA) and its metabolites (dihydroxyphenylacetic acid, DOPAC, and homovanillic acid, HVA) and serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) using HPLC/EC. Relative to the ad lib. group, restricted rats of both sex showed significant decreases in NE content in CN, HYPO and OB. DA and 5-HT content were decreased significantly in the CN and HYPO. No significant changes were found in the levels of DA metabolites in all brain regions studied. While the 5-HIAA level was significantly reduced in the HYPO and NA of the female restricted rats, it was increased several-fold in the OB of the male restricted animals. These preliminary results suggest that long-term caloric restriction alters brain monoamine concentrations, an effect which may in turn modify the normal rate of aging.

Aging↗

Automated conductimetric assay of human serum cholinesterase activity.

Serum cholinesterase activity was determined by conductimetry using samples in the microliter range. Butyrylcholine iodide was demonstrated to be a convenient substrate for the conductimetric assay. Validation of the microassay was made by using either purified enzyme or control serum. In the range of 0-60 U/l, a linear relationship was demonstrated. Correlation with a reference spectrophotometric method was obtained with a slope of 1.18. An explanation of this value is proposed, as different hydrolysis rates were obtained with human sera, depending on the substrate used (butyrylthio- or butyryl-choline ester).

Autoanalysis↗

Regulation of the mesocorticolimbic dopamine system by glutamic acid receptor subtypes.

Glutamic acid and excitatory amino acids specific for the glutamate receptor subtypes were microinjected into the A10 region of the rat. Glutamate produced an increase in motor behavior that was antagonized by pretreatment with the dopamine D2 receptor antagonist, haloperidol. This motor stimulant effect was produced by kainate, but not by N-methyl-D-aspartate (NMDA) or quisqualic acid. By using in vivo dialysis it was found that dopamine release in the nucleus accumbens and locomotor activity were enhanced by glutamate injection into the A10 region. Whereas glutamate was found to increase the postmortem concentration of dopamine metabolites in the medial prefrontal cortex, nucleus accumbens and A10 region, NMDA selectively increased dopamine metabolism in the prefrontal cortex, and kainate produced increases in the nucleus accumbens and A10 region. When glutamate and the NMDA receptor antagonist, 3-[(+/-)-2-carboxypiperazine-4-yl)propyl-1-phosphonic acid (CPP) were coadministered, CPP selectively abolished the effect of glutamate on medial prefrontal cortical dopamine metabolites. A physiological role for the NMDA receptor modulation of A10 dopamine neurons was shown by intra-A10 pretreatment with CPP antagonism of mild footshock-induced increase in dopamine metabolites in the prefrontal cortex. These data argue that glutamate is a regulatory transmitter of A10 dopamine neurons, and that the NMDA receptor subtype modulates neurons projecting to the prefrontal cortex whereas the kainate subtype modulates mesoaccumbens neurons.

Amino Acids↗

Detection of poisoning by plant-origin cardiac glycoside with the Abbott TDx analyzer.

Cardiac glycoside poisoning caused by ingestion of plant material is common in tropical and sub-tropical areas. In evaluating the use of the Abbott TDx Digoxin II assay to detect such cases of poisoning, we found it a rapid and convenient method for confirming the ingestion of glycosides from the plants Nerium oleander, Thevetia peruviana, and Adonis microcarpa, and from the toad Bufo marinus. Here we report some clinical cases illustrating our experience with the use of this assay, and describe results of cross-reactivity studies with compounds structurally similar to digoxin. Because of the competitive nature of the immunoassay as well as the complexity of the mixture of cross-reacting cardiac glycosides present in the plant material, the measured apparent digoxin concentration is not linearly related to the cardiac glycoside concentration.

Adolescent↗

Familial Alzheimer's disease with myoclonus and 'spongy change'.

"Spongy change," or vacuolar change, was observed in the neocortex of temporal and frontal lobes in four of 27 patients with clinical and pathologic characteristics of Alzheimer's disease. All four cases had the autosomal dominant form of the disease, and aside from severe dementia, all developed myoclonus and became mute before death. The degeneration observed was unlike that seen in Creutzfeldt-Jakob disease because it lacked astrocytosis and had a different distribution of lesions. Moreover, the abundance of neurofibrillary changes and senile plaques was consistent with Alzheimer's disease. None of the other 23 cases were familial, and none developed myoclonus or mutism; three of them had minor vacuolation limited to the temporal lobe. The four cases with severe spongy change described are the first, to our knowledge, in which vacuolar or spongy change has been associated with the familial form of Alzheimer's disease.

Aged↗

Effects of daily cocaine and morphine treatment on somatodendritic and terminal field dopamine release.

Daily injections of cocaine or morphine into rodents produces behavioral sensitization such that the last daily injection results in a greater motor stimulant effect than the first injection. To evaluate a role for brain dopamine in behavioral sensitization to cocaine and morphine, tissue slices from the ventromedial mesencephalon (containing dopamine cell bodies), the nucleus accumbens, and striatum (dopamine terminal fields) were obtained from rats pretreated with daily cocaine, morphine, or saline 2-3 weeks earlier. When the tissue slices were depolarized by increasing potassium concentration in the superfusate, the release of endogenous dopamine from the ventromedial mesencephalon of cocaine- and morphine-pretreated rats was significantly decreased. In contrast, the release of dopamine from the nucleus accumbens and striatum was either unaltered or slightly enhanced in rats pretreated with cocaine and morphine. When dopamine was released by amphetamine, a significant decrease in dopamine release from the ventromedial mesencephalon of cocaine-pretreated rats was measured. No other significant changes were measured after amphetamine-induced release. It is postulated that the decrease in dopamine release from the ventromedial mesencephalon of cocaine- and morphine-sensitized rats results in less somatodendritic autoreceptor stimulation, and thereby produces an increase in dopamine neuronal activity.

3,4-Dihydroxyphenylacetic Acid↗

A study of the cells in the explanted viable cryopreserved allograft valve.

From June 1975 to December 1987, 231 patients underwent aortic valve replacement with a viable cryopreserved allograft aortic valve. Throughout this era, a uniform procurement and preservation was used to maintain leaflet fibroblast viability. The allograft valve was obtained from coroner's autopsies within 24 hours of death, and more recently from organ donors, incubated for 24 hours in low dose antibiotic solution followed immediately by cryopreservation (mean time interval 39 hours after donor death). Viability was ensured by monitoring glucose utilization of the aortic and pulmonary valves and by demonstrating fibroblast growth in tissue cultured from the pulmonary valve. A uniform protocol for valve preparation was used during the entire experience. Nine allograft aortic valves have been obtained by eight reoperations (two were for leaflet degeneration) and one autopsy. The time intervals from implantation to explantation were 2 months, 10 months, 20 months, 22 months, 2.2 years, 5 years, 8.3 years, 9.2 years, and 10.8 years. Histologic examination of the leaflet tissue disclosed a variable degree of cellularity, ranging from a highly cellular matrix (9.2 years) to minimal cellularity (20 months). Within the same valve (10 months), one leaflet was completely acellular with a moderate degree of cellularity in the other two leaflets. The competent valve recovered at autopsy (8.2 years) was essentially acellular. Fibroblasts could consistently be cultured from leaflets in which viable cells were seen histologically. Chromosomal analysis of cultured cells from a valve leaflet (9.2 years) that was implanted with a donor and recipient sex mismatch demonstrated persistence of donor cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Aortic Valve↗