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Biomedical subjects

D G Watson

Publications and source records attributed to D G Watson.

At least 55 records · Page 3Linked to original sources
PubMed1999

Effect of oral administration of vitamin C on human aqueous humor ascorbate concentration.

AIM: To study oral administration of vitamin C on human aqueous humour ascorbate concentration. METHODS: High performance liquid chromatography (HPLC) coupled with electrochemical detector (ECD) was used. The effect of oral administration of various doses of ascorbic acid, 0 (control), 1.0, 1.5, 2.0, 3.0, and 5.0 g, on its concentration in aqueous humour, obtained from volunteer cataract patients was studied. RESULTS: The concentration of ascorbic acid in aqueous humour of control group (without administration of vitamin-C tablet or drug containing ascorbic acid was (254 +/- 119) mg.L-1. This study revealed that the administration of 2.0 g of ascorbic acid saturate the aqueous humour and further increase in the dose (3.0 g and 5.0 g) did not increase its concentration in aqueous humour, although its concentration was increased in plasma. CONCLUSION: Oral administration of 2.0 g of Vc is sufficient to saturate the aqueous humour where it may be helpful in controlling the intra-ocular pressure.

Aged↗
PubMed1998

Analysis of flavonoids in tablets and urine by gas chromatography/mass spectrometry and liquid chromatography/mass spectrometry.

A method was developed for the analysis and characterization of quercetin and kaempferol in urine following ingestion of Ginkgo biloba tablets. The method utilized gas chromatography/negative ion chemical ionization mass spectrometry of the trimethysilyl derivatives of the flavonoids. Limits of detection for these compounds using this method were ca. 20 pg on column. Liquid chromatography with electrospray mass spectrometry in the negative ion mode was utilized to characterize the complex mixture of glycosides present in the G. biloba tablets, the limit of detection with this technique was ca. 10 ng on column.

Chromatography, High Pressure Liquid↗
PubMed1998

The effect of praziquantel treatment on glutathione concentration in Schistosoma mansoni.

A fluorescent dye monochlorobimane (MCB) that binds glutathione (GSH) was used as a tool for measuring the concentration of GSH in skin and mechanically-transformed schistosomula. The specificity of MCB binding to GSH was confirmed by thin layer chromatography (TLC) and high performance liquid chromatography (HPLC). The MCB binding to GSH is an energy-dependent process since no labelling could be seen at low temperature. When 24-h-old schistosomula were depleted of GSH by buthionine sulfoximine (a specific inhibitor of GSH synthesis) for 18 h, a significant decrease (P < 0.001) in fluorescence was observed. PZQ treatment of the schistosomula after first labelling the parasites with MCB did not greatly affect MCB binding to GSH. However, when the 24-h-old schistosomula were first PZQ treated and afterwards labelled with MCB, the pattern of labelling was identical to that of those of the non-labelled parasites. When 24-h-old schistosomula were first PZQ treated, washed and labelled in the presence of 1 mM GSH, the level of fluorescence was recovered. These results suggest that PZQ depletes GSH from schistosomula, and may render them susceptible to the host's immune system.

Animals↗
PubMed1998

Visual marking of moving objects: a role for top-down feature-based inhibition in selection.

Recently, the authors presented evidence that new items can be prioritized for selection by the top-down attentional inhibition of old stimuli already in the field (visual marking; D. G. Watson & G. W. Humphreys, 1997). In this article the authors assess whether this inhibition extends to moving old items and test an alternative account of visual marking. Six experiments showed that old moving items could be inhibited provided they did not undergo abrupt property changes. Further, and in contrast to effects with static stimuli, the marking of old moving stimuli was based on inhibition applied at the level of a whole feature map, rather than at their locations. The results also rule out an alternative account of visual marking based on the top-down weighting of dynamic or static processing pathways.

Adolescent↗
PubMed1998

Sodium valproate down-regulates the myristoylated alanine-rich C kinase substrate (MARCKS) in immortalized hippocampal cells: a property of protein kinase C-mediated mood stabilizers.

Sodium valproate (VPA) is a short-chain fatty acid with well-established anticonvulsant properties and apparent clinical efficacy in the treatment of bipolar disorder (manic-depressive illness). Little is known regarding the mechanism of action of VPA in the brain that could account for this clinical therapeutic profile. Lithium has been the standard treatment for bipolar disorder, and it is known to be an uncompetitive inhibitor of inositol monophosphatase in the phosphoinositide (PI) signaling cascade at clinically relevant concentrations. Recent studies have provided data in support of a role for protein kinase C and the down-regulation of expression of the myristoylated alanine-rich C kinase substrate (MARCKS) in the long-term therapeutic action of lithium in the brain, which is dependent on both the relative activity of receptor-coupled PI signaling and the concentration of myo-inositol. Our current results demonstrated that valproate induces a concentration- and time-dependent reduction of MARCKS in immortalized hippocampal cells that appears to be independent of both the level of muscarinic receptor-activated PI signaling as well as the concentration of myo-inositol. In CHO-K1 cells transfected with the human m1 muscarinic receptor, unlike lithium, there is no evidence for receptor-mediated accumulation of CMP-PA in the presence of VPA, providing more direct data for its lack of interaction within the PI signaling cascade. The action of VPA on MARCKS occurs within the therapeutic concentrations and time course observed in clinical studies of patients with bipolar disorder. Furthermore, the effect on MARCKS protein is additive in the presence of therapeutic concentrations of both lithium and valproate, consistent with clinical observations regarding the enhanced efficacy of the combination treatment. Finally, in studies examining acute and chronic effects of a variety of psychotropic compounds and VPA structural analogs, it is evident that the property of regulation of MARCKS is shared by the mood-stabilizers lithium and VPA, which may be specific to a class of drugs effective in the treatment of bipolar disorder.

Animals↗
PubMed1997

Determination of molecular weight of hyaluronic acid in bovine vitreous humour and Healon by high performance gel permeation chromatography and its depolymerization with ascorbic acid.

A method has been developed for the determination of the molecular weight of hyaluronic acid by high performance gel permeation chromatography. The molecular weight distribution was determined using three polymeric columns. Columns were calibrated using Pullulan Polymer molecular weight standards. The average molecular weight (+/- SD) of the hyaluronic acid in bovine vitreous humour and Healon were 1.20 x 10(6) Da (+/- 0.49 x 10(6) and 3.01 x 10(6) Da (+/- 0.14 x 10(6), respectively. Furthermore, the depolymerization of the hyaluronic acid in the presence of ascorbic acid (the concentration found in human eye) was studied. Samples incubated in the presence of atmospheric air showed more depolymerization than those where atmospheric air had been flushed-out with nitrogen.

Animals↗
PubMed1997

Visual marking: prioritizing selection for new objects by top-down attentional inhibition of old objects.

The authors propose a new mechanism for prioritizing the selection of new events: visual marking. In a modified conjunction search task the authors presented one set of distractors before the remaining items, which contained the target if present. Search was as efficient as if only the second items were presented. This held when eye movements were prevented and required a gap of 400 ms between the old and new items. The effect was abolished by luminance changes at old distractor locations when the new items appeared, and it was reduced by the addition of an attention demanding load task. The authors propose that old items can be ignored by spatially parallel, top-down attentional inhibition applied to the locations of static stimuli. The authors discuss the relations between marking and other accounts of visual selection and potential neurophysiological mechanisms.

Adolescent↗
PubMed1996

Synthesis and characterisation of acyl glycines. Their measurement in single blood spots by gas chromatography-mass spectrometry to diagnose inborn errors of metabolism.

Acyl glycines are normally minor metabolites of fatty acids; however, the excretion of certain acyl glycines is increased in several inborn errors of metabolism. Therefore measurement of the metabolites in body fluids can be used to diagnose these metabolic disorders. The chemical synthesis of a range of acyl glycines is described, together with that of their 13C2-isotopomers for use as internal standards. An analytical method for the measurement of hexanoyl, octanoyl, 3-phenylpropionyl and suberyl glycines in urine, employing gas chromatography-mass spectrometry with negative-ion chemical ionisation was adapted to measure a larger range of acyl glycines in a single blood spot on a standard Guthrie card. Diagnoses of a case of medium-chain acyl-CoA dehydrogenase deficiency and a case of isovaleric acidaemia were confirmed using a single blood spot from each patient.

Calibration↗
PubMed1996

Bioavailability of subcutaneous 5-fluorouracil: a case report.

The optimal schedule for the administration of 5-fluorouracil (5-FU) in the management of advanced colorectal cancer remains to be determined. It has been suggested that this drug may be given by the subcutaneous route and that following a short infusion the bioavailability is similar to that observed after intravenous administration. We report the results we obtained in a patient treated with an intravenous bolus of 5-FU followed by a 22-h subcutaneous infusion. In this patient the bioavailability of 5-FU given by subcutaneous infusion was 0.94. The steady-state plasma levels of 5-FU reached during subcutaneous infusion were comparable with those achieved during intravenous infusion. Following four cycles of subcutaneous therapy, painless blistering was noted at the infusion sites, which healed following the cessation of subcutaneous therapy. Further studies are required to evaluate this route of therapy as an alternative to protracted intravenous therapy. The main dose-limiting side effect appears to the local skin toxicity.

Antidotes↗
PubMed1996

Comparative study of the determination of bupivacaine in human plasma by gas chromatography-mass spectrometry and high-performance liquid chromatography.

A comparison was made between high-performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS) as methods for determining bupivacaine in human plasma. Both methods utilized pentycaine as an internal standard, were found to be linear in the range 5-320 ng and had acceptable precision and accuracy. The precision for the HPLC method was better than that for the GC-MS method. The limits of detection of the HPLC and GC-MS methods were ca. 1.0 and 0.1 ng, respectively. Good agreement between the HPLC and GC-MS methods was obtained for the analysis of samples taken from a patient receiving bupivacaine topically. For most purposes the HPLC method would be slightly better. However, for samples containing interfering peaks GC-MS provides a higher degree of resolution from such interferants.

Administration, Topical↗
PubMed1996

Chronic lithium-induced down-regulation of MARCKS in immortalized hippocampal cells: potentiation by muscarinic receptor activation.

Previous studies in our laboratory have demonstrated that exposure of rats to chronic lithium results in a significant reduction in the hippocampus of levels of the protein kinase C (PKC) phosphoprotein substrate MARCKS (myristoylated alanine-rich C kinase substrate), which persists after withdrawal and is not observed following acute administration. In an immortalized hippocampal cell line (HN33), we have determined that phorbol esters rapidly down-regulate PKC activity and lead to a subsequent PKC-dependent reduction in content of MARCKS protein. We now report that chronic exposure of HN33 cells to LiCl (1-10 mM) produces a dose- and time-dependent down-regulation of MARCKS protein. The lithium-induced reduction in MARCKS is dependent on the concentration of inositol present in the medium and is reversed and prevented in the presence of elevated inositol concentrations. When HN33 cells were exposed to lithium at clinically relevant concentrations (11 mM) under limiting inositol conditions, activation of muscarinic receptor-coupled phosphoinositide signaling significantly potentiated the lithium-induced down-regulation of MARCKS protein. It has been suggested that a major action of lithium in the brain is linked to its inositol monophosphatase inhibitory activity in receptor-mediated signaling through the inositol trisphosphate/diacylglycerol pathway, resulting in a relative inositol depletion. Our data provide evidence that this initial action of lithium may translate into a PKC-dependent long-term down-regulation of MARCKS protein expression in the hippocampus.

Animals↗
PubMed1996

Myristoylated alanine-rich C kinase substrate (MARCKS): a molecular target for the therapeutic action of mood stabilizers in the brain?

BACKGROUND: Lithium remains a first-line treatment for the acute and prophylactic management of bipolar illness. Previous studies in our laboratory have demonstrated that chronic, but not acute, exposure to therapeutic concentrations of lithium significantly reduces the expression of the protein kinase C (PKC) substrate MARCKS (myristoylated alanine-rich C kinase substrate) in the rat hippocampus and an immortalized hippocampal cell line (HN33). The anticonvulsant drugs valproate and carbamazepine are emerging as efficacious alternative and adjunctive treatments for bipolar disorder. In the present study, we sought to determine the effects of valproate and carbamazepine on MARCKS protein levels by using our hippocampal cell model. METHOD: HN33 immortalized hippocampal cells were exposed acutely or chronically to sodium valproate 1 mM, carbamazepine 100 microM, lithium chloride 5 mM, or lithium chloride 5 mM + sodium valproate 1 mM. Additionally, cells were exposed to lithium chloride 5 mM in the absence or presence of inositol 5 microM, or sodium valproate 1 mM in the absence or presence of inositol 40 microM. After drug exposure, cells were collected, separated into soluble and membrane fractions, and MARCKS protein assayed by Western blot analysis using polyclonal rabbit antibody. Immunoreactive bands were quantitated by densitometric analysis. RESULTS: We report that chronic exposure of HN33 cells to either lithium or valproate produced a time-dependent down-regulation of MARCKS protein. Maximal reduction in MARCKS levels were observed after 3 days of exposure to valproate and after 7 days of exposure to lithium. The reduction of MARCKS produced by lithium and valproate alone were additive when the two drugs were combined. The reduction in MARCKS produced by lithium was reversed by the addition of inositol to the media, whereas the reduction produced by valproate was unaffected by the addition of inositol. Carbamazepine failed to affect MARCKS protein levels at each dose and time tested. CONCLUSION: These data provide evidence that, like lithium, chronic exposure to valproate produces a significant time-dependent down-regulation of the PKC substrate MARCKS, whereas carbamazepine is without effect. The MARCKS reduction produced by valproate appears to occur independently of inositol concentrations yet is additive with the reduction produced by lithium, which is inositol-reversible. Valproate- and lithium-induced regulation of MARCKS expression appears to be mediated by different mechanisms that may utilize PKC, and may be associated with the clinical profile of these mood stabilizers. Regulation of MARCKS expression may be associated with the prophylactic efficacy of lithium in the long-term stabilization of the recurrent affective episodes in bipolar disorder, and valproate may share this property.

Animals↗
PubMed1995

Analysis of unconjugated morphine, codeine, normorphine and morphine as glucuronides in small volumes of plasma from children.

A sensitive method for the analysis of unconjugated morphine, codeine, normorphine and total morphine after hydrolysis of glucuronide conjugates is described. The method was applicable to 50-microliters volumes of plasma. The analytes were converted to heptafluorobutyryl (HFB) derivatives before analysis by gas chromatography-negative ion chemical ionization mass spectrometry. Morphine and codeine were quantified against their [2H3]-isotopomers. Linearity, precision and accuracy were quite acceptable (in the 10(-10)-10(-9) g range), and the absolute limits of detection were < 1 pg.

Child↗
PubMed1995

Metabolism by Schistosoma mansoni of a new schistosomicide: 2-[(1-methylpropyl)amino]-1-octanethiosulphuric acid.

In order to investigate the mode of action of a new class of schistosomicides, the N-alkylaminoalkanethiosulphuric acids, the [outer 25S] 2-[(1-methylpropyl)amino]-1-octanethiosulphuric acids was synthesized. Labelling studies of adult Schistosoma mansoni were performed in infected mice and in in vitro incubations. After a single oral dose of the drug to infected mice, 5 metabolites were detected by thin-layer chromatogrpahy in organic extracts of male and female adult schistosomes. In vitro studies showed that the same compounds were present in organic extracts obtained from adult male and female worms. One of these metabolites was identified by mass spectroscopy as being the dimeric disulphide derivative of the parent labelled thiosulphuric acid.

Animals↗
PubMed1995

Attention capture by contour onsets and offsets: no special role for onsets.

In five experiments, we investigated the power of targets defined by the onset or offset of one of an object's parts (contour onsets and offsets) either to guide or to capture visual attention. In Experiment 1, search for a single contour onset target was compared with search for a single contour offset target against a static background of distractors; no difference was found between the efficiency with which each could be detected. In Experiment 2, onsets and offsets were compared for automatic attention capture, when both occurred simultaneously. Unlike in previous studies, the effects of overall luminance change, new-object creation, and number of onset and offset items were controlled. It was found that contour onset and offset items captured attention equally well. However, display size effects on both target types were also apparent. Such effects may have been due to competition for selection between multiple onset and offset stimuli. In Experiments 3 and 4, single onset and offset stimuli were presented simultaneously and pitted directly against one another among a background of static distractors. In Experiment 3, we examined "guided search," for a target that was formed either from an onset or from an offset among static items. In Experiment 4, the onsets and offsets were uncorrelated with the target location. Similar results occurred in both experiments: target onsets and offsets were detected more efficiently than static stimuli which needed serial search; there remained effects of display size on performance; but there was still no advantage for onsets. In Experiment 5, we examined automatic attention capture by single onset and offset stimuli presented individually among static distractors. Again, there was no advantage for onset over offset targets and a display size effect was also present. These results suggest that, both in isolation and in competition, onsets that do not form new objects neither guide nor gain automatic attention more efficiently than offsets. In addition, in contrast to previous studies in which onsets formed new objects, contour onsets and offsets did not reliably capture attention automatically.

Adolescent↗
PubMed1994

Phorbol ester- and retinoic acid-induced regulation of the protein kinase C substrate MARCKS in immortalized hippocampal cells.

The expression of MARCKS, a major protein kinase C (PKC) substrate, was examined in the immortalized hippocampal cell line HN33, following differentiation using phorbol esters or retinoic acid. In cells exposed to phorbol esters, MARCKS protein levels were reduced through an apparent PKC-dependent mechanism. Exposure to 1 microM phorbol 12-myristate 13-acetate (PMA) for 10 min resulted in a rapid loss of PKC activity in the soluble fraction with a concurrent increase in membrane-associated PKC activity. PKC activity was reduced to < 20% of control values in both soluble and membrane fractions following 1 h of PMA exposure. Significant reductions in MARCKS protein levels were initially observed in membrane and soluble fractions following PMA exposure for 4 and 8 h, respectively. The reduction in MARCKS protein levels was maximal following 24 h of PMA exposure. MARCKS protein expression was also down-regulated in a dose-dependent manner on exposure of HN33 cells to retinoic acid. In cells exposed to 10 microM retinoic acid, the MARCKS protein level was reduced in the membrane fraction within 4 h. Reduction of MARCKS protein levels was maximal (> 90%) by 12 h with no evidence for any alteration in PKC activity. Reduced levels of MARCKS protein were also observed in the soluble fraction of retinoic acid-exposed cells, but to a significantly lesser extent. Addition of the PKC inhibitor GF109203X blocked the down-regulation of MARCKS protein in PMA-treated cultures but not in retinoic acid-treated cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗