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Biomedical subjects

G Edwards

Publications and source records attributed to G Edwards.

At least 55 records · Page 3Linked to original sources
PubMed2001

The efficacy of problem-solving communication training alone, behavior management training alone, and their combination for parent-adolescent conflict in teenagers with ADHD and ODD.

Two family therapies were compared using teens with attention-deficit/hyperactivity disorder. Ninety-seven families were assigned to either 18 sessions of problem-solving communication training (PSCT) alone or behavior management training (BMT) for 9 sessions followed by PSCT for 9 sessions (BMT/PSCT). Both treatments demonstrated significant improvement in ratings of parent-teen conflicts at the midpoint but did not differ. By posttreatment, both produced improvement on ratings and observations but did not differ. Significantly more families dropped out of PSCT alone than out of BMT/PSCT. At most, 23% of families showed reliable change either by midpoint or by posttreatment, with no differences between therapies. Yet 31%-70% of families were normalized. Group-level change and normalization rates support treatment efficacy, whereas indices of reliable change are less impressive.

Adolescent↗
PubMed2000

Synthesis and antimalarial activity of sixteen dispiro-1,2,4, 5-tetraoxanes: alkyl-substituted 7,8,15,16-tetraoxadispiro[5.2.5. 2]hexadecanes.

Sixteen alkyl-substituted dispiro-1,2,4,5-tetraoxanes (7,8,15, 16-tetraoxadispiro[5.2.5.2]hexadecanes) were synthesized to explore dispiro-1,2,4,5-tetraoxane SAR and to identify tetraoxanes with better oral antimalarial activity than prototype tetraoxane 1 (WR 148999). The tetraoxanes were prepared either by peroxidation of the corresponding cyclohexanone derivatives in H(2)SO(4)/CH(3)CN or by ozonolysis of the corresponding cyclohexanone methyl oximes. Those tetraoxanes with alkyl substituents at the 1 and 10 positions were formed as single stereoisomers, whereas the five tetraoxanes formed without the stereochemical control provided by alkyl groups at the 1 and 10 positions were isolated as mixtures of diastereomers. Three of the sixteen tetraoxanes were inactive (IC(50)'s > 1000 nM), but five (2, 6, 10, 11, 12) had IC(50)'s between 10 and 30 nM against the chloroquine-sensitive D6 and chloroquine-resistant W2 clones of Plasmodium falciparum compared to corresponding IC(50)'s of 55 and 32 nM for 1 and 8.4 and 7.3 nM for artemisinin. We suggest that tetraoxanes 13, 16, and 17 were inactive and tetraoxanes 4 and 7 were weakly active due to steric effects preventing or hindering peroxide bond access to parasite heme. Tetraoxanes 1, 10, 11, and 14, along with artemisinin and arteether as controls, were administered po b.i.d. (128 mg/kg/day) to P. berghei-infected mice on days 3, 4, and 5 post-infection. At this dose, tetraoxanes 10, 11, and 14 cured between 40% and 60% of the infected animals. In comparison, artemisinin and tetraoxane 1 produced no cures, whereas arteether cured 100% of the infected animals. There was no apparent relationship between tetraoxane structure and in vitro neurotoxicity, nor was there any correlation between antimalarial activity and neurotoxicity for these seventeen tetraoxanes.

Alkanes↗
PubMed2000

3-Morpholinosydnonimine (SIN-1) and K(+) channels in smooth muscle cells of the rabbit and guinea pig carotid arteries.

Experiments were designed to determine the subtype of K(+) channels activated by the nitrovasodilator 3-morpholinosydnonimine (SIN-1) in smooth muscle cells of the rabbit and guinea pig carotid arteries. Membrane potential was recorded in isolated segments with intracellular microelectrode and K(+) currents in freshly dissociated smooth muscle cells, with the patch-clamp technique. In the guinea pig carotid artery, SIN-1 caused a glibenclamide-sensitive hyperpolarization. The nitrovasodilator did not affect the whole-cell K(+) current, but activated a glibenclamide-sensitive K(+) current. In the rabbit carotid artery, SIN-1 induced only an iberiotoxin-sensitive repolarization in phenylephrine-depolarized tissue and in isolated cells, enhanced the activity of an iberiotoxin-sensitive K(+) current. These findings demonstrate that the population of K(+) channels activated by nitric oxide (NO) is species-dependent and support the conclusion that, in the guinea pig carotid artery, in contrast to the rabbit carotid artery, the release of NO cannot account for the responses attributed to endothelium-derived hyperpolarizing factor (EDHF).

Animals↗
PubMed2000

Posthysterectomy vault prolapse.

The incidence of vault prolapse is uncertain but appears to be increased five fold after vaginal hysterectomy. A precise scoring system has now been devised to overcome the diagnosis and classification of this condition. Conservative measures may be used to treat this condition in women unfit for surgery or those who require symptomatic relief while awaiting surgery. The surgical options lie between a vaginal sacrospinous fixation, or abdominal procedures such as sacrocolpopexy or vault suspension operations. The success rate for these operations is over 90%. Pre-operative urodynamic evaluation is mandatory since these patients frequently have concomitant stress urinary incontinence which may require correction at the same time. The choice of operation will undoubtedly depend upon the experience of the surgeon but greater awareness and alteration of technique at the time of the original hysterectomy may be the better solution to reducing the incidence of vault prolapse.

Female↗
PubMed2000

Influence of ascorbate and the Mehler peroxidase reaction on non-photochemical quenching of chlorophyll fluorescence in maize mesophyll chloroplasts.

Non-photochemical quenching of chlorophyll fluorescence (NPQ) and quantum yield of photosystem II (PSII) were studied with intact mesophyll chloroplasts of maize (Zea mays L.) during the initial minutes of illumination using the pulse-modulated chlorophyll fluorescence technique. Non-photochemical quenching was rapidly reversible in the dark at any point during illumination, which is indicative of energy-dependent dissipation of energy (mediated via thylakoid delta pH changes and ascorbate-dependent synthesis of zeaxanthin). In chloroplasts suspensions including 15 mM ascorbate in the medium, with addition of oxaloacetate and pyruvate, the PSII yield, rate of reduction of oxaloacetate and phosphorylation of pyruvate reached a maximum after approximately 2 min of illumination. Under these conditions, which promote phosphorylation and a decreased delta pH across the thylakoid membrane, NPQ rose to a maximum after 2-3 min of illumination, dropped to a minimum after about 6 min, and then increased to a steady-state level. A rather similar pattern was observed when leaves were illuminated following a 30-min dark period. Providing chloroplasts with higher levels of ascorbate (60 mM), prevented the transient drop in NPQ. Anaerobic conditions or addition of potassium cyanide caused a decrease in PSII yield, providing evidence for operation of the ascorbate-dependent Mehler-peroxidase reaction. These conditions also strongly suppressed the transient drop in NPQ. Dithiothreitol, an inhibitor of violaxanthin de-epoxidase, caused a large drop in NPQ even in the presence of high levels of ascorbate. The results suggest that the decline of NPQ occurs in response to an increase in lumen pH after initiation of phosphorylation, that this decline can be suppressed by conditions where ascorbate is not limiting for violaxanthin de-epoxidase, and that the increase of NPQ after such a decline is the result of development of energy dissipation in PSII reaction centers.

Anaerobiosis↗
PubMed2000

Role of endothelial cell hyperpolarization in EDHF-mediated responses in the guinea-pig carotid artery.

1. Experiments were performed to identify the potassium channels involved in the acetylcholine-induced endothelium-dependent hyperpolarization of the guinea-pig internal carotid artery. Smooth muscle and endothelial cell membrane potentials were recorded in isolated arteries with intracellular microelectrodes. Potassium currents were recorded in freshly-dissociated smooth muscle cells using patch clamp techniques. 2. In single myocytes, iberiotoxin (0.1 microM)-, charybdotoxin (0.1 microM)-, apamin (0.5 microM)- and 4-aminopyridine (5 mM)-sensitive potassium currents were identified indicating the presence of large- and small-conductance calcium-sensitive potassium channels (BK(Ca) and SK(Ca)) as well as voltage-dependent potassium channels (K(V)). Charybdotoxin and iberiotoxin inhibited the same population of BK(Ca) but a conductance specifically sensitive to the combination of charybdotoxin plus apamin could not be detected. 4-aminopyridine (0. 1 - 25 mM) induced a concentration-dependent inhibition of K(V) without affecting the iberiotoxin- or the apamin-sensitive currents. 3. In isolated arteries, both the endothelium-dependent hyperpolarization of smooth muscle and the hyperpolarization of endothelial cells induced by acetylcholine or by substance P were inhibited by 5 mM 4-aminopyridine. 4. These results indicate that in the vascular smooth muscle cells of the guinea-pig carotid artery, a conductance specifically sensitive to the combination of charybdotoxin plus apamin could not be detected, comforting the hypothesis that the combination of these two toxins should act on the endothelial cells. Furthermore, the inhibition by 4-aminopyridine of both smooth muscle and endothelial hyperpolarizations, suggests that in order to observe an endothelium-dependent hyperpolarization of the vascular smooth muscle cells, the activation of endothelial potassium channels is likely to be required.

4-Aminopyridine↗
PubMed2000

Role of gap junctions and EETs in endothelium-dependent hyperpolarization of porcine coronary artery.

1. The effects of endothelium-derived hyperpolarizing factor (EDHF: elicited using substance P or bradykinin) were compared with those of 11,12-EET in pig coronary artery. Smooth muscle cells were usually impaled with microelectrodes through the adventitial surface. 2. Substance P (100 nM) and 11,12-EET (11,12-epoxyeicosatrienoic acid; 3 microM) hyperpolarized endothelial cells in intact arteries. These actions were unaffected by 100 nM iberiotoxin but were abolished by charybdotoxin plus apamin (each 100 nM). 3. Substance P (100 nM) and bradykinin (30 nM) hyperpolarized intact artery smooth muscle; Substance P had no effect after endothelium removal. 11,12-EET hyperpolarized de-endothelialized vessels by 12.6+/-0.3 mV, an effect abolished by 100 nM iberiotoxin. 4. 11,12-EET hyperpolarized intact arteries by 18.6+/-0.8 mV, an action reduced by iberiotoxin, which was ineffective against substance P. Hyperpolarizations to 11, 12-EET and substance P were partially inhibited by 100 nM charybdotoxin and abolished by further addition of 100 nM apamin. 5. 30 microM barium plus 500 nM ouabain depolarized intact artery smooth muscle but responses to substance P and bradykinin were unchanged. 500 microM gap 27 markedly reduced hyperpolarizations to substance P and bradykinin which were abolished in the additional presence of barium plus ouabain. 6. Substance P-induced hyperpolarizations of smooth muscle cells immediately below the internal elastic lamina were unaffected by gap 27, even in the presence of barium plus ouabain. 7. In pig coronary artery, 11,12-EET is not EDHF. Smooth muscle hyperpolarizations attributed to 'EDHF' are initiated by endothelial cell hyperpolarization involving charybdotoxin- (but not iberiotoxin) and apamin-sensitive K(+) channels. This may spread electrotonically via myoendothelial gap junctions but the involvement of an unknown endothelial factor cannot be excluded.

8,11,14-Eicosatrienoic Acid↗
PubMed2000

Relative contribution of cytochromes P-450 and flavin-containing monoxygenases to the metabolism of albendazole by human liver microsomes.

AIMS: Albendazole (ABZ; methyl 5-propylthio-1H-benzimidazol-2-yl carbamate) is a broad spectrum anthelmintic whose activity resides both in the parent compound and its sulphoxide metabolite (ABS). There are numerous reports of ABZ metabolism in animals but relatively few in humans. We have investigated the sulphoxidation of ABZ in human liver microsomes and recombinant systems. METHODS: The specific enzymes involved in the sulphoxidation of ABZ were determined by a combination of approaches; inhibition with an antiserum directed against cytochrome P450 reductase, the effect of selective chemical inhibitors on ABZ sulphoxidation in human liver microsomes, the capability of expressed CYP and FMO to mediate the formation of ABS, regression analysis of the rate of metabolism of ABZ to ABS in human liver microsomes against selective P450 substrates and regression analysis of the rate of ABS sulphoxidation against CYP expression measured by Western blotting. RESULTS: Comparison of Vmax values obtained following heat inactivation (3min at 45 degrees C) of flavin monoxygenases (FMO), chemical inhibition of FMO with methimazole and addition of an antiserum directed against cytochrome P450 reductase indicate that FMO and CYP contribute approximately 30% and 70%, respectively, to ABS production in vitro. Comparison of CLint values suggests CYP is a major contributor in vivo. A significant reduction in ABZ sulphoxidation (n = 3) was seen with ketoconazole (CYP3 A4; 32-37%), ritonavir (CYP3 A4: 34-42%), methimazole (FMO: 28-49%) and thioacetamide (FMO; 32-35%). Additive inhibition with ketoconazole and methimazole was 69 +/- 8% (n = 3). ABS production in heat - treated microsomes (3 min at 45 degrees C) correlated significantly with testosterone 6beta-hydroxylation (CYP3A4; P < 0.05) and band intensities on Western blots probed with an antibody selective for 3A4 (P < 0.05). Recombinant human CYP3 A4, CYP1A2 and FMO3 produced ABS in greater quantities than control microsomes, with those expressing CYP3A4 producing threefold more ABS than those expressing CYP1A2. Kinetic studies showed the Km values obtained with both CYP3A4 and FMO3 were similar. CONCLUSIONS: We conclude that the production of ABS in human liver is mediated via both FMO and CYP, principally CYP3A4, with the CYP component being the major contributor.

Albendazole↗
PubMed2000

Chloroquine and desethylchloroquine concentrations in blood cells and plasma from Indian patients infected with sensitive or resistant Plasmodium falciparum.

The sensitivities of 61 Indian cases of Plasmodium falciparum malaria to chloroquine (CQ) were investigated using in-vitro and in-vivo methods. Concentrations of CQ and desethylchloroquine (DCQ) in blood cells and plasma from CQ-sensitive and -resistant cases were determined 2 and 7 days after initiation of treatment, by HPLC. On day 2, the mean CQ concentrations in the samples collected from the sensitive cases were higher than those in the samples from the resistant patients, in plasma (0.47 v. 0.32 microgram/ml; P < 0.02) and particularly in the blood cells (1.51 v. 0.46 micrograms/ml; P < 0.001). By day 7, however, the CQ concentrations in the two groups were similar. Although, on day 2, the mean ratio of the CQ to DCQ concentrations was significantly higher in the blood cells from the sensitive group than in those from the resistant cases (P < 0.01), the CQ/DCQ ratios for the plasma were similar for the two groups. Similarly, the mean ratio between the blood-cell concentration of CQ on day 2 and the concurrent plasma concentration (BPr) was also relatively high in the sensitive group (P < 0.001).

Adult↗
PubMed2000

The alcohol supply: its importance to public health and safety, and essential research questions.

This paper seeks to identify the main questions which have emerged from the preceding papers concerning the supply side of alcohol. On any rational analysis these issues are of thoroughly legitimate concern to public health researchers. We list them under seven headings: (1) what drives the alcohol supply side? (2) What is the impact of alcohol supply on demand? (3) What are the benefits and risks to health and safety stemming from deregulation and what are the possibilities to avoid negative effects? (4) What is the size and significance of the alcohol supply which may derive from other than the officially approved channels? (5) Who are the important actors in the alcohol supply system? (6) What are local influences on alcohol supply and its distribution throughout communities? (7) What is to be learned from tobacco and other risky commodities about the importance of supply? Finally, we outline a series of possible next steps for a supply side initiative.

Alcohol Drinking↗