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Biomedical subjects

B A Hayes

Publications and source records attributed to B A Hayes.

11 recordsLinked to original sources
PubMed2001

Perinatal depression: a randomized controlled trial of an antenatal education intervention for primiparas.

BACKGROUND: Depression can be an unexpected and distressing companion for a woman during the major life transition of becoming a mother for the first time. Researchers now demonstrate that approximately 50 percent of women will experience perinatal distress. Therefore, the etiology and management of perinatal depression is essential for a quality care of childbearing women. The objectives of this study were to develop an education intervention tailored to the information needs of primiparous women about perinatal depression, to deliver this intervention antenatally, and to conduct a randomized controlled trial to determine the effect of the antenatal education intervention in the reduction of postnatal depression. METHOD: A prospective, randomized controlled trial of the education intervention (n = 206) was conducted at three sites in Australia. The outcome of changes in mood state was measured by the Profile of Mood States questionnaire once antenatally (12-28 wk), and twice postnatally (8-12 and 16-24 wk); social support and demographic data were also collected. The education package was administered to the intervention group at the antenatal assessment of mood. RESULTS: A significant and steady reduction in scores (overall and on the subscales) was observed over time for both groups that showed significant improvement in symptoms of depression. No difference was detected when comparing the intervention group with the control group. Additional multivariate regression analyses revealed no relevant influence of social support or demographic variables. CONCLUSIONS: Women in both the study and control groups were more depressed antenatally than postnatally. The finding that the education intervention made no difference challenges the two strongly held tenets of health education in childbearing women-that depression can be reduced through education and that antenatal education interventions can endure into the postnatal period.

Adult↗
PubMed1999

Evaluation of the reinforcing properties and phencyclidine-like discriminative stimulus effects of dextromethorphan and dextrorphan in rats and rhesus monkeys.

RATIONALE: Dextromethorphan (DXM) and its metabolite, dextrorphan (DXO) have neuroprotective and anticonvulsant properties through their activity as N-methyl-D-aspartate (NMDA) receptor channel blockers. Based on this receptor activity, coupled with reports of DXM abuse, both were evaluated for abuse potential and phencyclidine (PCP)-like behavioral effects in two animal models. OBJECTIVES AND METHODS: The discriminative stimulus properties of DXO and DXM were tested in rats (3-56 mg/kg DXM, i.p. and 2.2-40.9 mg/kg DXO, i.p.) and rhesus monkeys (0.3-10 mg/kg DXM, i.m. and 0.25-8.0 mg/kg DXO, i. m.) trained to discriminate PCP from saline using a standard two-lever drug-discrimination paradigm under a fixed-ratio (FR) schedule of food reinforcement. In a second set of experiments, i.v. self-administration of DXO (10-100 microg/kg/infusion) and DXM (10-1000 microg/kg/infusion) were tested under a FR schedule of reinforcement in monkeys trained to lever press for infusions of PCP during daily 1-h sessions. RESULTS: In rats, both DXM and DXO produced a dose-dependent substitution for PCP. When tested in monkeys, DXM yielded partial (1 monkey) and full (2 monkeys) substitution for PCP, while DXO substituted fully for PCP in all four subjects tested. In the self-administration study, in five of the six subjects, at least one dose of DXM served as a positive reinforcer, maintaining infusion rates above those for saline. For DXO, at least one dose maintained infusion numbers well above mean saline infusion numbers in all subjects. CONCLUSIONS: Taken together, these data show that DXM has some PCP-like effects in rats and monkeys, but that they are more reliably produced by its metabolite, DXO. Thus, high doses of DXM may have some PCP-like abuse potential in humans but this potential may be associated with, or enhanced by, metabolism of DXM to DXO.

Animals↗
PubMed1993

Regulation of endothelin-1 expression in normal and transfected endothelial cells.

Calcium phosphate precipitation and retrovirus-mediated infection methods were used to stably infect bovine pulmonary artery endothelial cells (BPAECs) with mammalian expression vectors bearing human prepro-ET-1 cDNA. The calcium phosphate precipitation method afforded a stably transfected cell line that expressed approximately four times higher ET-1 than untransfected BPAEC by radioimmunoassay and at the mRNA level. The retrovirus-mediated transfection method yielded stably infected clones that secreted eightfold to 10-fold higher ET-1 than the nontransfected BPAECs; one clone continued to produce 10-fold higher levels after continuous assay for 1 year. Both transfected and nontransfected cells showed an increase (approximately twofold) in ET-1 production in response to thrombin (10 U/ml). Downregulation of ET-1 production was exhibited by both transfected and nontransfected cells in response to nitric oxide (NO) donors: sodium nitroprusside (NOPr), S-nitroso-N-acetoxy penicillamine (SNAP), and acetoxime. The potentiation of NO by superoxide dismutase (SOD) also downregulated ET-1 production. These studies show that an exogenous gene introduced into a cell type that normally expresses that gene product can be regulated by agonists and antagonists in a manner similar to the normal gene regulatory mechanisms for that cell type. This is of potential importance in gene therapy experiments, where mechanisms for regulation of expression remain elusive.

Animals↗
PubMed1992

Interleukin-2 directly increases albumin permeability of bovine and human vascular endothelium in vitro.

The direct effects of interleukin-2 (IL-2) on albumin permeability of cultured bovine pulmonary artery endothelial cell (BPAEC) and human arterial endothelial cell (HAEC) monolayers were studied. BPAEC were exposed to IL-2 (500 to 25,000 U/ml) for 4 h. The steady-state transfer rate of [125I]albumin across the BPAEC monolayer was 3.3 +/- 0.4%/h (n = 10) in control BPAEC (diluent alone), was significantly increased in BPAEC exposed to 500 U/ml of IL-2 (72 +/- 3% above control values, n = 6, P less than 0.02), and further increased in BPAEC exposed to 5,000 U/ml (60 +/- 2% increase above 500 U/ml values, n = 5, P less than 0.02). No further increase was noted after exposure to 25,000 U/ml of IL-2. Additionally, no further increase in [125I]albumin transfer rates was noted in BPAEC exposed to 5,000 U/ml of IL-2 for 24 versus 4 h. Similar changes were found using HAEC. Preincubation of HAEC with an anti-IL-2 low-affinity receptor antibody (anti-IL-2R alpha) inhibited the IL-2-induced permeability increase. Expression of IL-2R alpha receptors in HAEC incubated with 5,000 U/ml of IL-2 for 4 h was also found. Thus, IL-2 appears to have a direct effect on cultural arterial endothelial monolayers not requiring the presence of other cell types or serum proteins. IL-2-induced increases in endothelial macromolecular permeability may play an important role in the pathogenesis of the IL-2-induced vascular leak syndrome seen in vivo.

Albumins↗
PubMed1990

The self-administration of MK-801 can depend upon drug-reinforcement history, and its discriminative stimulus properties are phencyclidine-like in rhesus monkeys.

The proposed noncompetitive N-methyl-D-aspartate antagonist MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5,10-imine maleate] has therapeutic potential as an anticonvulsant and neuroprotectant. Previous research has demonstrated that MK-801 shares many of the biochemical and pharmacological actions of the abused drug phencyclidine (PCP). The purpose of the present study was to determine whether rhesus monkeys would self-administer i.v. MK-801 and to determine whether MK-801 has discriminative stimulus properties similar to those of PCP. Four Rhesus monkeys were trained to press response levers according to fixed-ratio 10 schedules of reinforcement for infusions of cocaine (33 micrograms/kg/injection) or PCP (10 micrograms/kg/injection). Various doses of MK-801 were evaluated during substitution tests to determine whether they would maintain lever pressing. None of the four rhesus monkeys tested self-administered MK-801 when it was offered to them after a recent history of cocaine self-administration. Three of the four monkeys, however, did self-administer MK-801 when provided a history of PCP self-administration. All four rhesus monkeys given drug discrimination training with 80 micrograms/kg PCP and tested with MK-801 generalized from the PCP stimulus in a dose-dependent manner. MK-801 was about 2 to 3 times more potent and had a longer duration of action than PCP. Overall, these results provide further evidence in a primate species of similarities in the behavioral effects of MK-801 and PCP, and suggest that MK-801 may have abuse potential of the PCP type.

Animals↗
PubMed1989

Dual-phase response of bovine pulmonary artery endothelial cells to agonists which increase free cytoplasmic calcium concentration.

The regulation of free cytoplasmic calcium concentration ([Ca2+]i) was studied in bovine pulmonary artery endothelial cells (BPAEC). The cells were seeded on the inner surface of glass cuvettes, grown to confluency and loaded with INDO-1. Using a multiwavelength method for estimation of [Ca2+]i it was shown that in Ca2+ containing medium a rapid rise of [Ca2+]i occurs in response to bradykinin, ATP or thrombin followed by a much slower decrease in free cytoplasmic calcium. Binding of extracellular Ca2+ by EGTA lowered basal [Ca2+]i but had no effect on the rate of agonist-induced [Ca2+]i increase or its absolute amount. In contrast, the kinetics of [Ca2+]i decrease were entirely different. A rapid (less than 0.5 min) decrease in [Ca2+]i to the basal level was observed immediately after the maximum had been achieved. If excess Ca2+ was added to the medium after EGTA, a second [Ca2+]i rise in response to the agonists occurred. The decrease in [Ca2+]i after the second peak was several times slower than the decrease in Ca2+ free medium. It is concluded that Ca2+ entry from the external medium had no effect on the maximal increase in [Ca2+]i but provides a severalfold increase in the duration the endothelial cell responses to the agonists.

Adenosine Triphosphate↗
PubMed1985

Anticonvulsant properties of phencyclidine-like drugs in mice.

Primarily on the basis of activity in [3H]phencyclidine (PCP) binding assays and drug discrimination studies, a number of structurally dissimilar compounds have been found to be PCP-like. Drugs from four of these classes of PCP-like compounds were examined for anticonvulsant activity in the pentylenetetrazol (PTZ) seizure test. Male albino mice, eight per dose, were administered the drug or vehicle i.p. 10 min before PTZ (125 mg/kg s.c.). At each dose, the number of subjects and latency to clonic and/or tonic seizures within 15 min following PTZ were recorded. The anticonvulsant properties of PCP, ketamine, (+)-N-allylnormetazocine, etoxadrol, dexoxadrol and (-)-2-methyl-3,3-diphenyl-3-propanolamine ((-)-2-MDP) were selective for tonic seizures. The highest dose tested for each compound completely prevented the occurrence of tonic seizures. Levoxadrol and (+)-2-MDP, drugs devoid of PCP-like activity in other tests, were also inactive in the PTZ seizure test. These results demonstrate that similarities among PCP-like drugs previously shown using binding assays and drug discrimination procedures can be extended to include anticonvulsant effects, and they suggest common cellular sites of action for these properties.

Animals↗