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1.
Neuropharmacology ; 48(2): 236-45, 2005 Feb.
Article in English | MEDLINE | ID: mdl-15695162

ABSTRACT

Functional magnetic resonance imaging (fMRI), employing BOLD-contrast, was used to measure changes in regional brain activation following amphetamine administration, either alone or after pre-treatment with the dopamine D1 receptor antagonist SCH23390, or the dopamine D2 receptor antagonist, sulpiride, in anaesthetised rat. After obtaining baseline data, rats (n=8) were given amphetamine (3 g/kg i.v) and volume data sets collected for 90 mins. Acute amphetamine challenge caused widespread increases in BOLD signal intensity in many subcortical structures with rich dopaminergic innervation, with decreases in BOLD contrast observed in the superficial layers of the cortex. Pretreatment with SCH23390 (n=8, 0.5 mg/kg, i.v) substantially attenuated the increases in BOLD activity in response to amphetamine, with lesser effects on the amphetamine-evoked decreases in BOLD signal. In contrast, sulpiride (n=8, 50 mg/kg, i.v) predominantly blocked the decrease in BOLD signal, having a smaller effect on the increases in BOLD signal. In summary, these data are supportive of the notion that different dopamine receptor types are responsible for separate components of the full amphetamine response. Furthermore the utility of BOLD contrast fMRI as a means of characterising the mechanisms of drug action in the whole brain has been demonstrated. Such studies may be of particular use for investigation of localised action and interaction of different dopaminergic agents.


Subject(s)
Amphetamine/pharmacology , Dopamine Antagonists/pharmacology , Magnetic Resonance Imaging/methods , Receptors, Dopamine/metabolism , Animals , Benzazepines/metabolism , Benzazepines/pharmacology , Dopamine Antagonists/metabolism , Male , Rats , Rats, Sprague-Dawley , Sulpiride/metabolism , Sulpiride/pharmacology
2.
Water Sci Technol ; 48(2): 349-56, 2003.
Article in English | MEDLINE | ID: mdl-14510230

ABSTRACT

The most economic combination of unit treatment processes for a new sewage treatment works in Zimbabwe was found to be anaerobic ponds followed by trickling filters. The regulations governing irrigation with treated effluent permitted the omission of humus tanks or further treatment. Two stage anaerobic ponds are desludged by gravity through fixed sludge outlet pipework. Sludge is disposed of by irrigation of a Eucalyptus plantation. Novel features of the inlet works and pond outlets are also described. The works has functioned for eight years without major problems, but the assumption that humus tanks or settling ponds were not required may have been mistaken. The sludge removal system has worked well. Without the sludge pipework, it is estimated that desludging of the primary ponds would have been required after two years of operation, but they have now operated successfully for eight years. The combination of anaerobic ponds and trickling filters should be considered where land availability or site conditions make facultative ponds difficult or expensive to construct.


Subject(s)
Bacteria, Anaerobic/physiology , Waste Disposal, Fluid/methods , Bioreactors , Conservation of Natural Resources , Eucalyptus , Filtration , Sewage , Water Pollution/prevention & control , Water Supply , Zimbabwe
3.
Eur J Clin Pharmacol ; 35(3): 287-94, 1988.
Article in English | MEDLINE | ID: mdl-3181281

ABSTRACT

The pharmacokinetics of low-dose aspirin and the resulting salicylic acid were studied in 6 healthy volunteers. Each received a single 50-mg dose of (1) oral modified release capsules, (2) oral solution and (3) intravenous solution. The volunteers also received 50 mg modified release capsules daily for 6 days to determine the effect on collagen, ADP and arachidonate induced platelet aggregation and thromboxane production, and to compare the pharmacokinetics after repeated dosing with the parameters obtained after the single dose. The formulation and route of administration profoundly influenced several pharmacokinetic parameters for aspirin: the maximum concentration (Cmax, ng.ml-1) was 221 and 191 after modified release for single and chronic dosing respectively, 1323 after the oral solution and 6000 after intravenous injection; the time to achieve this maximum concentration (tmax, h) was 3.42 and 3.02 after modified release for single and chronic dosing respectively, and 0.29 after the oral solution; the area under the plasma drug concentration versus time curve (AUC, microgram.h.ml-1) was 0.38 and 0.27 after modified release single and chronic dosing respectively, 0.68 after the oral solution and 1.57 after intravenous injection. The elimination of aspirin after the two solutions was at least biphasic. The terminal phase rate constant ranged from 1.52 h-1 after intravenous injection to 1.88 h-1 after the oral modified release form. The absorption of the oral forms of aspirin was complete as reflected by the total recovery of the doses as salicylic acid in urine.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Aspirin/pharmacokinetics , Platelet Aggregation/drug effects , Thromboxane A2/biosynthesis , Administration, Oral , Adult , Aspirin/administration & dosage , Aspirin/blood , Female , Humans , Injections, Intravenous , Kinetics , Male , Middle Aged , Salicylates/blood , Salicylates/urine , Salicylic Acid
4.
Cancer ; 56(1): 25-36, 1985 Jul 01.
Article in English | MEDLINE | ID: mdl-2988735

ABSTRACT

The accuracy of scintigraphy in diagnosing hepatocellular carcinoma (HCC) at Boston City Hospital between January 1, 1978 and September 30, 1983 is retrospectively reviewed. A combined protocol using technetium-99m sulfur colloid (TsSC), gallium (Ga), and scintiangiography (STA) was employed in order to enhance diagnostic specificity. There were 14 cases of HCC, of which 10 were proven histologically. The others were diagnosed clinically and angiographically. With one exception, all patients who had triple tracer scintigraphy showed a specific pattern of findings: (1) cold defects with TcSC; (2) Ga-avid foci, and (3) increased vascular supply from hepatic arteries. One false-positive study and one false-negative study were originally reported, although in both cases, strict adherence to the three criteria above would have avoided diagnostic error. These results indicate that triple tracer scintigraphy may be an effective diagnostic test for HCC. The relative efficacy of scintigraphy, ultrasonography, and computerized tomography in diagnosing HCC is also discussed.


Subject(s)
Carcinoma, Hepatocellular/diagnostic imaging , Gallium Radioisotopes , Liver Neoplasms/diagnostic imaging , Technetium , Adult , Aged , Carcinoma, Hepatocellular/blood supply , Diagnosis, Differential , Diagnostic Errors , Erythrocytes , Female , Hepatic Artery/diagnostic imaging , Humans , Liver Diseases/diagnostic imaging , Liver Neoplasms/blood supply , Liver Neoplasms/secondary , Male , Middle Aged , Radionuclide Imaging , Retrospective Studies , Technetium Tc 99m Sulfur Colloid
5.
AJR Am J Roentgenol ; 143(1): 57-61, 1984 Jul.
Article in English | MEDLINE | ID: mdl-6328961

ABSTRACT

Four consecutive cases of proven hepatocellular carcinoma (HCC) showed significant avidity of 99mTc -labeled iminodiacetic acids (Tc- IDAs ) in preoperative scintigraphy. In one patient, the pulmonary metastasis showed uptake of Tc-IDA. Such scintigraphic findings were obvious only in the delayed scans, performed 2 1/2-4 hr after injection. Since Tc- IDAs and bilirubin are functional analogs physiologically, the ability of HCC to concentrate Tc- IDAs may be related to the ability of HCC neoplastic cells to form bile intracellularly. This hypothesis is supported by the fact that intracellular bile granules were found in the tumor cells of all four patients. This suggests a potential for using Tc- IDAs for the specific and preoperative diagnostic of HCC.


Subject(s)
Carcinoma, Hepatocellular/diagnostic imaging , Imino Acids , Liver Neoplasms/diagnostic imaging , Technetium , Adult , Bile/metabolism , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/secondary , Humans , Liver Neoplasms/metabolism , Liver Neoplasms/secondary , Male , Middle Aged , Radionuclide Imaging , Technetium Tc 99m Disofenin , Technetium Tc 99m Lidofenin
6.
J Cardiovasc Pharmacol ; 3(3): 409-19, 1981.
Article in English | MEDLINE | ID: mdl-6168823

ABSTRACT

The antiarrhythmic effects of intravenously administered lignocaine and mexiletine were compared over a period of 48 hr in a randomized trial on 24 patients who developed ventricular tachyarrhythmias within 48 hr of the onset of acute myocardial infarction. Mexiletine was given as an initial bolus of 200 mg, followed by an infusion of 1 mg/min reduced to 0.5 mg/min after 1 hr. Lignocaine was given as a bolus of 100 mg, followed by an infusion of 3 mg/min reduced to 2 mg/min after 1 hr. Plasma levels of mexiletine, lignocaine, and monoethylglycinexylidide were monitored. The frequency of "complex" ventricular tachyarrhythmias was significantly lower in the mexiletine-treated group. This group of patients also had significantly fewer ventricular extrasystoles than those receiving lignocaine, the difference being most marked during the second 24 hr of treatment. Too few episodes of ventricular fibrillation occurred for statistical comment. The greater efficacy of mexiletine was not associated with increased drug toxicity.


Subject(s)
Arrhythmias, Cardiac/drug therapy , Lidocaine/therapeutic use , Mexiletine/therapeutic use , Myocardial Infarction/complications , Propylamines/therapeutic use , Tachycardia/drug therapy , Adult , Aged , Clinical Trials as Topic , Female , Humans , Lidocaine/blood , Male , Mexiletine/blood , Middle Aged
7.
J Pharm Sci ; 70(3): 320-2, 1981 Mar.
Article in English | MEDLINE | ID: mdl-7264901

ABSTRACT

A sensitive assay is described for the calcium antagonist perhexiline maleate. Alkalinized plasma was extracted with nb-hexane, the organic phase was evaporated, and the residue was dansylated prior to analysis by reversed-phase high-performance liquid chromatography using a fluorescence detector. Perhexiline was resolved from its mono- and dihydroxylated metabolites, and the limit of sensitivity was 5 ng of perhexiline/ml. This limit represents approximately 100 times the sensitivity of the previously described GLC assay. Single-dose pharmacokinetic studies were performed with 150- and 300-mg oral doses of perhexiline maleate in five patients with severe angina pectoris and impaired left ventricular function. Peak plasma perhexiline levels occurred 3-6 hr after drug ingestion in four patients and after 12-18 hr in the fifth patient. The mean elimination half-life, measured 24 hr after drug ingestion, varied with plasma perhexiline concentration. It was 11.2 +/- 2.1 hr after the 150-mg dose and 19.1 +/- 2.8 hr after the 300-mg dose. The mean ratio of areas under the concentration-time curve for the 300-versus 150-mg doses ws 5.3:1, suggesting that hepatic metabolism of perhexiline may be saturable and that the bioavailability of perhexiline is dose dependent.


Subject(s)
Perhexiline/blood , Piperidines/blood , Aged , Chromatography, High Pressure Liquid , Dose-Response Relationship, Drug , Half-Life , Humans , Perhexiline/administration & dosage , Time Factors
9.
Clin Exp Pharmacol Physiol ; 5(1): 67-73, 1978.
Article in English | MEDLINE | ID: mdl-346272

ABSTRACT

1. A precise and rapid gas chromatographic method for the measurement of plasma sodium valproate concentrations is presented. 2. The extraction is a single step procedure, and is reproducible and linear throughout the concentration range encountered. 3. Clinical evaluation of the drug is presented in eighteen epileptics on the basis of the percentage of days on which subjects had seizures before and after sodium valproate therapy. 4. A tentative therapeutic range for sodium valproate is presented on the basis of plasma levels and therapeutic effect.


Subject(s)
Epilepsy/drug therapy , Valerates/blood , Valproic Acid/blood , Chromatography, Gas , Epilepsy/blood , Humans , Methods , Valproic Acid/therapeutic use
10.
Clin Exp Neurol ; 15: 145-53, 1978.
Article in English | MEDLINE | ID: mdl-386306

ABSTRACT

Individual dose-plasma level relationships were studied in 14 chronically treated epileptics, 10 of whom were concomitantly receiving other anticonvulsants besides valproate. Linear regression analysis showed each individual relationship to be linear with correlation co-efficients ranging from 0.9137 to 0.9997. A considerable inter-individual variation was found to exist in the slopes of the regression lines (range: 0.86 to 5.72). This may be the consequence of differences in absorption characteristics and metabolic handling of the drug. The results indicate that a proportional rise in plasma sodium valproate levels can be expected following dosage increments in an individual patient. Hourly plasma sodium valproate measurements for 6 hours between 2 successive doses, in the same group of patients, showed that the mean percentage change in post-dose peak plasma levels was 44.5%, and range from 20.7 to 153.5%. Plasma levels returned to values close to pre-dose starting levels 6 hours after the administration of a dose. The large degree of inter-dose fluctuation between doses indicates that it is preferable to use pre-dose plasma sodium valproate levels to guide the clinical management of epileptic patients.


Subject(s)
Epilepsy/drug therapy , Valproic Acid/blood , Adolescent , Adult , Anticonvulsants/administration & dosage , Child , Drug Therapy, Combination , Epilepsy/blood , Female , Humans , Male , Regression Analysis , Valproic Acid/administration & dosage
11.
Clin Chim Acta ; 74(3): 261-9, 1977 Feb 01.
Article in English | MEDLINE | ID: mdl-401696

ABSTRACT

Serum concentration of cortisol, growth hormone, thyroxine, thyroid stimulating hormone, follicle stimulating hormone and luteinising hormone, together with triiodothyronine uptake have been measured in Nigerian children with kwashiorkor and marasmus and compared with controls. In both types of malnutrition the cortisol and growth hormone concentrations are raised, whereas those of thyroxine and thyroid stimulating hormone are lowered compared with the controls. Triiodothyronine uptake is lowered in malnutrition but there is no apparent effect on follicle stimulating hormone or luteinising hormone in this age group.


Subject(s)
Endocrine Glands/physiopathology , Protein-Energy Malnutrition/physiopathology , Child, Preschool , Follicle Stimulating Hormone/blood , Growth Hormone/blood , Humans , Hydrocortisone/blood , Infant , Kwashiorkor/blood , Kwashiorkor/physiopathology , Luteinizing Hormone/blood , Pituitary Gland/physiopathology , Protein-Energy Malnutrition/blood , Thyroid Gland/physiopathology , Thyroxine/blood , Triiodothyronine/blood
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