Transvaginal pulsed Doppler ultrasound assessment of blood flow to the corpus luteum in IVF patients following embryo transfer.
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Corpus Luteum↗
Biomedical subjects
R Gill
Publications and source records attributed to R Gill.
The neuroprotective action of dizocilpine (MK-801) in the rat middle cerebral artery occlusion model of focal ischaemia.
1. An acute model of focal ischaemia, which involves permanent occlusion of the middle cerebral artery of the rat with 4 h survival, was used to find the minimum effective plasma concentration of dizocilpine (MK-801) and to determine its dose-effect relationship. 2. MK-801 was administered at the time of occlusion and was given as an i.v. bolus followed by an infusion for 4 h to maintain a steady state plasma concentration of the drug throughout the study. MK-801 was given at 3 dose levels; 0.04 mg kg-1 i.v. bolus + 0.6 micrograms kg-1 min-1 infusion; 0.12 mg kg-1 i.v. bolus + 1.8 micrograms kg-1 min-1 infusion; 0.4 mg kg-1 i.v. bolus + 6 micrograms kg-1 min-1 infusion, which gave mean plasma levels over the 4 h of 8.0 ng ml-1, 18.9 ng ml-1 and 113.2 ng ml-1 respectively. 3. MK-801 at 8.0 ng ml-1 gave 10% reduction in the volume of ischaemic brain damage in the cerebral cortex which just reached significance. The middle dose of MK-801 (18.9 ng ml-1) gave a highly significant reduction in the volume of ischaemic brain damage in the cerebral cortex and hemisphere, volumes of ischaemic tissue being reduced by 60% and 50% compared to saline-treated animals, respectively. The highest plasma concentration of MK-801 (113.2 ng ml-1) resulted in a 35% reduction in the volume of hemispheric damage and a 40% reduction in the volume of cortical damage, which were significant.4. The reduction in the amount of protection afforded by the highest dose of MK-801 may be due to the hypotensive effect of this dose. There was no protection against the volume of damage in the caudate nucleus for any of the doses of MK-801 tested.5. Therefore the minimum effective plasma concentration of MK-801 was 8.0 ngml1, although the greatest protection was seen with a plasma level of 18.9 ng ml- 1. This correlates well with the concentration of MK-801 required to block N-methyl-D-aspartate (NMDA) receptors and prevent NMDA receptor mediated neurotoxicity in vitro.
Animals↗
The response of evidential breath alcohol testing instruments with subjects exposed to organic solvents and gases. I. Toluene, 1,1,1-trichloroethane and butane.
Experimental work has been undertaken to investigate the potential interference of toluene, 1,1,1-trichloroethane and butane with the evidential breath alcohol testing instruments used in Great Britain (Lion Intoximeter 3000 and Camic Breath Analyser). Volunteers inhaled the volatile substances in an exposure chamber for up to 4 hours, at concentrations of 100, 350 and 600ppm respectively. Subsequently breath was tested on leaving the chamber. No interference was observed with the breath alcohol instruments when the subjects were exposed to toluene and 1,1,1-trichloroethane. A short-term response immediately after exposure was observed for subjects exposed to butane. Further analytical work involving blood and breath samples demonstrated that all three volatile substances were absorbed during exposure and were detectable in blood for at least 3 hours post-exposure. Their elimination post-exposure followed an exponential decay.
Adult↗
The response of evidential breath alcohol testing instruments with subjects exposed to organic solvents and gases. II. White spirit and nonane.
Following exposure to white spirit vapour, the effect of the expired solvent on evidential breath alcohol equipment was investigated under controlled exposure chamber conditions and in a simulated painting exercise. Five volunteers inhaled the solvent in an exposure chamber at a concentration of 100ppm for periods up to 4h 17min. Two other volunteers were exposed to white spirit while painting with domestic gloss paint in an unventilated room under which conditions exposure concentrations reached 185ppm for 20min. Following all white spirit exposures, volunteers underwent breath tests with the Lion Intoximeter 3000. In all instances the apparent alcohol responses were very small and never exceeded a reading of 1 microgram/100ml for breath samples more than 10min post-exposure. Simultaneous analytical work was conducted to demonstrate that white spirit was absorbed during exposure and was present in the breath and blood after the volunteers had left the exposure atmospheres. A further study involved the exposure of a volunteer to nonane vapour at 100ppm, demonstrating that this compound, being one of the principal components of white spirit, appears to be a good model for studying the uptake and elimination of white spirit.
Adult↗
The response of evidential breath alcohol testing instruments with subjects exposed to organic solvents and gases. III. White spirit exposure during domestic painting.
The concentration of white spirit vapour in the breathing zone of a volunteer engaged in domestic painting activities has been investigated. Air was continuously sampled and analysed using an infra-red gas analyser (Miran) during painting experiments. Both indoor and outdoor painting tasks were undertaken using commercial paints in a wide variety of situations. For each task the time weighted average (TWA) exposure has been determined. In no case did the TWA exposure exceed the Occupational Exposure Limit-Long Term Exposure Limit (OEL-LTEL) of 100 ppm. The results have been used to discuss the significance of previous studies in which volunteers were exposed to white spirit vapour in an exposure chamber to test for possible interference in breath alcohol testing.
Breath Tests↗
The neuroprotective actions of kynurenic acid and MK-801 in gerbils are synergistic and not related to hypothermia.
The broad spectrum excitatory amino acid antagonist, kynurenic acid was evaluated in a transient forebrain ischaemia model in gerbils. When administered i.p., 15 min prior to a 5 min period of ischaemia, a dose-related neuroprotective effect was seen with 800 mg/kg of kynurenic acid showing very good protection. A combination of kynurenic acid (200 or 400 mg/kg) and MK-801 (0.1 mg/kg) gave a synergistic neuroprotective effect. Neither kynurenic acid (200 or 400 mg/kg) nor MK-801 (0.3 mg/kg) was neuroprotective when administered by itself 30 min post-ischaemically, but when co-administered significant protection of the CA1 pyramidal neurones of the hippocampus was seen. In addition, we examined the effect of maintaining core body temperature on the neuroprotective action of MK-801 and kynurenic acid following the suggestion that it was a hypothermic effect of MK-801 which resulted in neuroprotection in gerbils. When the body temperature of the gerbils was maintained at 37 degrees C for a period of 24 h it did not affect the neuroprotective action of MK-801 (0.1 or 10 mg/kg) or kynurenic acid (200 mg/kg).
Animals↗
Economics of mastitis control.
The frequency of use and the effects of mastitis control practices on SCC and milk yield were investigated. A survey of current management practices was combined with DHI production information to determine the relationship between milk yield, SCC, management practices, and production and producer characteristics under field conditions. The expected negative relationship between SCC and milk, fat, and protein yield was substantiated. The SCC for an individual cow was a better indicator of milk loss than was a bulk tank SCC. Most recommended mastitis control practices were estimated to be economically beneficial; however, using a sanitizer in the washing solution and having a company change the milking machine inflations were not economical. Questions were raised about the economic efficiency and efficacy of treating all cows as opposed to selected cows at drying off.
Animal Husbandry↗
Therapeutic potential of NMDA receptor antagonists as neuroprotective agents.
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Animals↗
Protection of CA1 pyramidal cell function by MK-801 following ischaemia in the gerbil.
Electrophysiological recordings were made from hippocampal slices of gerbils which had undergone a 5 min period of bilateral carotid occlusion. Normal CA1 population spikes, field potentials and synaptic responses were obtained from slices of gerbils pretreated with the N-methyl-D-aspartate antagonist, MK-801 (10 mg/kg, i.p., 1 h before the occlusion). In contrast, no CA1 population spike could be obtained from slices of untreated gerbils, although field potentials and population spikes were obtained from the dentate granule cell region of these slices in response to perforant path stimulation. These studies indicate that the CA1 pyramidal cells identified histologically as protected by MK-801 from selective neuronal degeneration produced by a 5 min period of global ischaemia, are also functionally protected and retain their normal synaptic responsiveness.
Animals↗
International collaborative study of the retention reproducibility of basic drugs in high-performance liquid chromatography on a silica column with a methanol-ammonium nitrate eluent.
An international collaborative study between 10 laboratories has been carried out to study the reproducibility of the separation of basic drugs on silica columns. The laboratories used common solutions of drugs on both a common batch of packing material and different batches of the same brand of packing material. These were also compared with separations on other brands of packing material. Variations within-batch, within-brand and between brands have been compared. The retentions of the drugs were compared using retention times, capacity factors and relative capacity factors compared with an internal standard. The last method was found to give the most reproducible results. Considerable variations were found between the different brands of silica with a smaller variation between the batches of a single silica brand. However, unlike earlier studies, significant variations were found for separations on a single batch of silica which were partly attributed to differences in eluent preparation and column temperature.
Chromatography, High Pressure Liquid↗
Molecular mechanism for the inhibitory action of interferon on hematopoiesis.
Spleen cell suspensions obtained from adult mice were separated by Ficoll/Hypaque and Percoll density gradient centrifugation. The enriched erythroblast populations were maintained in liquid culture medium for 8 hours with 10,000 units of murine interferon (IFN) alpha and beta. Exposure of these cell cultures to murine IFN alpha and beta resulted in a 48% to 70% increase in 2-5adenylate synthetase (2-5AS) activity. In parallel studies, adult mice were injected daily for 1 or 2 weeks with recombinant human IFN alpha A/D (rHuIFN alpha A/D) at a dose of 10(6) or 10(7) units/kg body weight. This treatment did not significantly affect body weight but did produce a mean 70% increase in spleen wet weight and a mean 46% increase in number of nucleated cells per spleen. This increase in number of splenic hematopoietic cells did not result in a corresponding increase in number of circulating cells. In fact, during this 1 to 2 week period the hematocrit dropped from 45% to 38% in mice injected with high dose rHuIFN alpha A/D. From these findings we propose that IFN induces an early 2-5AS activity in erythroblasts and megakaryocytes. This 2-5AS activity, which is known to inhibit protein synthesis in other cell systems, is thought to be responsible for the block or prolongation in blood cell maturation observed in the present studies.
Animals↗
Retention reproducibility of basic drugs in high-performance liquid chromatography on a silica column with a methanol-ammonium nitrate eluent. Batch-to-batch reproducibility of the stationary phase.
The effect of changing the brand and batches of the silica stationary phase used with a methanol-aqueous ammonium nitrate eluent for the high-performance liquid chromatographic separation of basic drugs has been studied. Considerable care had to be taken to obtain a reproducible eluent and the effect of small changes in the concentration of the ammonia solution were examined closely. Large differences in both the capacity factor and relative capacity factors were found for separations on columns packed with four different brands of silica. Significant differences were also observed with columns containing eighteen different batches of Spherisorb S5W, which had been manufactured over a period of several years.
Chromatography, High Pressure Liquid↗
Characterisation of acid dyes in forensic fibre analysis by high-performance liquid chromatography using narrow-bore columns and diode array detection.
A gradient elution high-performance liquid chromatographic (HPLC) system with a diode array detector and a short narrow-bore (40 x 1 mm I.D.) column has been used to characterise a number of acid dyes. The resolution and reproducibility of the HPLC system have been evaluated and the detection limits for various dyes have been estimated. Comparisons are made with current methods of fibre dyestuff examination used in forensic science. The system has been applied to the analysis of dye extracted from single fibres. Using diode array detection, both chromatographic and spectral data can be produced in a single operation from casework sized samples.
Animals↗
A semiautomated system for measurement of 96 simultaneous spectrophotometric enzyme assays.
A semiautomated system for spectrophotometric measurement of enzyme activity is described. In comparison to a 1-ml reaction volume monitored continuously by a conventional spectrophotometer, this system requires 1/10 to 1/100 the volume of sample, and 1/8 to 1/4 the time for measurement and computation of 96 enzyme assays. The system hardware consists of a 96-well platereader interfaced to a personal computer. Absorbances of 96 reactions are measured at timed intervals. These data are transmitted electronically from the platereader to the computer through the modem port using a modem program. The reaction rates are computed from the timed absorbance readings using a spreadsheet program. Three enzyme assays are presented, but the method has been used for several other assays and is applicable to many spectrophotometric rate assays. Many laboratories currently possess one or both of the two major components of the relatively inexpensive system described.
Animals↗
MK-801 is neuroprotective in gerbils when administered during the post-ischaemic period.
The neuroprotective effects of the non-competitive N-methyl-D-aspartate receptor antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801) have been evaluated in the gerbil hippocampus when the drug was administered i.p. at various times during and after a 5 min period of transient forebrain ischaemia, induced by bilateral common carotid artery occlusion. A single dose of 1, 3 or 10 mg/kg of MK-801 gave significant protection of hippocampal CA1 and CA2 pyramidal neurons when administered during the occlusion and up to 24 h following the period of ischaemia. A dose of 0.3 mg/kg was effective when administered during the occlusion period but gave no protection at 30 min or 2 h post-ischaemia. Experiments in which MK-801 was administered in repeated doses indicated that significant protection was achieved with 1 mg/kg of MK-801 repeated post-ischaemically and with 1 mg/kg MK-801 supplemented with repeated doses of 0.3 mg/kg of MK-801. However 0.3 mg/kg of MK-801 followed by repeated doses of 0.03 mg/kg administered post-ischaemically was not neuroprotective. These results indicate that MK-801 can protect hippocampal neurons from ischaemia-induced neuronal degeneration when it is administered up to 24 h after the insult. These data provide further evidence that therapeutic intervention in the post-ischaemic period can successfully prevent neurodegenerative events, and that the delayed degeneration of hippocampal neurons following an ischaemic insult occurs by an N-methyl-D-aspartate receptor-mediated process.
Animals↗
Neuroprotective effects of MK-801 in vivo: selectivity and evidence for delayed degeneration mediated by NMDA receptor activation.
The ability of the noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 to prevent neuronal degeneration in the rat striatum and hippocampus caused by intracerebral injection of excitotoxins has been examined. Excitotoxic damage was assessed after 7 d, using histological and biochemical [choline acetyltransferase (ChAT) glutamate decarboxylase (GAD)] measurements. Systemically administered MK-801 was found to protect against neurodegeneration caused by NMDA (200 nmol) and the naturally occurring NMDA receptor agonist quinolinate (120-600 nmol) but not against that induced by kainate (5 nmol) or alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA; 50 nmol), indicating a selectivity for NMDA receptor-mediated neuronal loss. Neurotoxicity caused by NMDA (200 nmol) or quinolinate (200 nmol) was prevented by MK-801 (1-10 mg/kg, i.p.) administered in a single dose after excitotoxin injection. In the striatum, significant protection of cholinergic neurons (assessed by ChAT measurements) was observed when MK-801 was given up to 5 hr after injection of NMDA or quinolinate, whereas protection of GABAergic neurons (assessed by GAD measurements) was obtained up to 2 hr. The results suggest that GABAergic neurons degenerate more rapidly than cholinergic neurons. The competitive NMDA receptor antagonist 3-[(+/-)-2-carboxypiperazin-4-yl]-propyl-1-phosphonate (100 mg/kg, i.p.) gave partial protection of striatal neurons when administered 1 hr after quinolinate injection. In the rat hippocampus, administration of 10 mg/kg MK-801 i.p. 1 hr after quinolinate injection caused almost complete protection of pyramidal and granule neurons, whereas the degeneration of CA3/CA4 pyramidal neurons caused by kainate injection was unaffected. These observations indicate that neurons in rat striatum and hippocampus do not die as an immediate consequence of exposure to high concentrations of NMDA agonists but that a delayed process is involved that requires NMDA receptor activation. In this respect, intracerebral injections of NMDA agonists may mimic the pathological changes that are thought to occur in the brain following periods of cerebral ischemia, where delayed neuronal degeneration occurs.
Anesthesia↗
Retention reproducibility of basic drugs in high-performance liquid chromatography on a silica column with a methanol-ammonium nitrate eluent. The effect of the mobile phase and the operating conditions.
The reproducibility of capacity factors and relative capacity factors are compared as methods for recording retentions for the high-performance liquid chromatography of basic drugs on a silica column with methanol-aqueous ammonium nitrate as the eluent. The effects of changing the column temperature and the ionic strength, pH and proportion of organic modifier in the eluent on the retentions and selectivity have been studied. The results suggest that the mobile phase and operating conditions must be closely defined in order to obtain results of adequate reproducibility to develop a data base of retention values for interlaboratory comparisons and/or for the identification of basic drugs.
Chemical Phenomena↗
Systemic administration of MK-801 prevents N-methyl-D-aspartate-induced neuronal degeneration in rat brain.
MK-801 is a novel, potent and selective non-competitive antagonist of the N-methyl-D-aspartate (NMDA) subtype of excitatory amino acid receptors. Pretreatment of rats with MK-801 (1-10 mg/kg, i.p.) prevented neuronal degeneration in the hippocampus and striatum caused by direct intracranial injections of NMDA (20-120 nmol), but did not protect against the loss of neurones induced by kainate (2.5 nmol) injected into the striatum. Thus, MK-801 is a selective antagonist of neuronal degeneration caused by excessive stimulation of NMDA receptors in vivo.
Animals↗