Biomedical subjects
Publications and source records attributed to D J Roberts.
Arguments about whether or not scalp hair should be washed prior to an analysis have not reached any suitable conclusion. The following work was intended to resolve this argument and indicate a suitable procedure with regard to washing. Cigarettes spiked with cadmium were used to contaminate hair in an attempt to show whether or not the cadmium in hair was exogeneous (unbound) or endogeneous (bound).
The pharmacological effects of a new benzamide derivative cinitapride, have been compared to those of metoclopramide in guinea-pig isolated ileum and longitudinal smooth muscle-myenteric plexus preparations treated with propranolol (3 microM). Cinitapride (EC50 = 0.74 microM) was 6 times more potent than metoclopramide (EC50 = 4.69 microM) in enhancing the twitch response of co-axially stimulated preparations and 11 times more potent in eliciting contractions in non-stimulated tissues, their respective EC50 values being 0.58 microM and 6.52 microM. These contractile effects of cinitapride and metoclopramide amounted to approximately 25% of the maximum response of the tissues to acetylcholine (1 microM). Neither cinitapride nor metoclopramide, in concentrations up to 10 microM, significantly affected concentration-response curves to exogenous acetylcholine or 5-hydroxytryptamine but both drugs elicited a concentration-dependent potentiation of the ileum responses to a fixed concentration (10 microM) of the ganglion stimulant dimethylphenylpiperazinium (DMPP). Analysis of the twitch-enhancing and contractile effects of cinitapride using a variety of drugs suggested that a common, prejunctional locus of action upon the cell bodies or axons of postganglionic, parasympathetic neurones of the myenteric plexus is involved in both of these responses. In hexamethonium (100 microM) and methysergide (0.1 microM)-treated longitudinal smooth muscle preparations desensitization or blockade of 5-hydroxytryptamine receptors using high concentrations of the same agonist (30 microM) or quipazine (10 microM) or the putative antagonists cocaine (30 microM) or tubocurarine (10 microM) produced small inhibitions (congruent to 20%) of the contractile responses to metoclopramide and cinitapride but did not affect twitch responses to these drugs. It is concluded that cinitapride is a more potent stimulant of guinea-pig intestinal smooth muscle than metoclopramide in vitro although the mechanism of action of both drugs appears to be similar and involves a prejunctional enhancement of acetylcholine release from intramural cholinergic neurones. Attempts to implicate a prejunctional facilitatory 5-hydroxytryptamine receptor in the mediation of the stimulant effects of these drugs were not conclusive and additional studies are required to fully explore this possibility.
Connective tissue activating peptide III (CTAP-III) is a platelet factor that induces, in cultured connective tissue cells, activities observed in chronic inflammation. In this study we measured plasminogen activator secretion by synovial fibroblasts after stimulation by CTAP-III. Increased plasminogen activator secretion was observed 24-48 hours after stimulation. Induction was prevented by dexamethasone (10(-9)-10(-7) M), cycloheximide (1 microgram/ml) and, variably, by actinomycin D (0.3 microgram/ml), but not by cytosine arabinoside (10(-4)M). This is the first evidence that CTAP-III induces degradative as well as proliferative activity by connective tissue cells.
Pharmacological screening tests have been done in order to provide an initial assessment of the new antacid compound almagate (aluminium-magnesium hydroxycarbonate hydrate, Al2Mg6(OH)14(CO3)2 X 4 H2O, Almax). In rats with pyloric ligatures, almagate (125-500 mg/kg) was significantly more potent than aluminium hydroxide in raising the pH and reducing the total acidity of the gastric juice produced, without affecting the volume secreted. Pepsin activity in the gastric juice was also significantly inhibited by almagate even after adjustment to the optimal enzyme pH 2, a phenomenon not demonstrable with aluminium hydroxide. Almagate in oral doses up to 3 g/kg was without effects on the central, autonomic and somatic nervous systems in mice, nor at 500 mg/kg did it influence the cardiovascular system or blood pressure responses to agonist drugs in anaesthetised cats. The results confirm almagate to be a potent antacid drug devoid of systemic pharmacological or toxicological effects.
The efficacies of almagate (hydrated aluminium-magnesium hydroxycarbonate, Al2Mg6(OH)14(CO3)2 X 4H2O, Almax) and aluminium hydroxide to neutralise histamine-induced gastric acid hypersecretion were compared in a closed-circuit perfused stomach preparation modified for pH-stat titration in the intact, anaesthetised rat. After intravenous injection of histamine (0.75 mg/kg), the amount of antacid automatically added to the closed system to maintain the stomach perfusion fluid at pH 4 was measured during 60 min. The results obtained show that the acid neutralising capacity of almagate in this hypersecretion model was some 8 times greater than that of aluminium hydroxide. Analysis of the titration curves obtained also demonstrates that the velocity of neutralisation to pH 4 at the start of the experiment was considerably more rapid with almagate. It is concluded that almagate will be a rapid acting, potent drug to reduce acidity of the gastric contents in conditions of acid hypersecretion.
In man, the reflux of duodenal contents into the stomach leads to gastritis and produces a mucosa susceptible to ulceration. This effect, predominantly due to bile acids, was studied in an animal model in which the oral administration of bile (ox bile powder containing a minimum of 45% cholic acid) markedly increased the gastrolesive action of subcutaneous indomethacin in the pylorus-ligated rat. Oral administration of the new antacid almagate (hydrated aluminium-magnesium hydroxycarbonate, Al2Mg6(OH)14 (CO3)2 X 4 H2O, Almax) gave a significant dose-related reduction in the severity of bile-facilitated gastric lesions whereas aluminium hydroxide gel did not. The antiulcer activity of almagate in this model is presumed to be attributable to its ability to sequester and inactivate bile acids at the pH of the stomach contents, an effect which should beneficially contribute to its acid-neutralising property in the treatment of gastritis, peptic ulcer and associated conditions.
In this study, virtually all sulfated glycosaminoglycan (GAG) synthesized and secreted by human synovial cells, both normal and rheumatoid, was detected in the form of proteoglycans of monomeric size. Enzyme hydrolysis studies that were performed demonstrated dermatan sulfate to be the dominant GAG in the proteoglycan, with lesser amounts of chondroitin 4/6 sulfate. Exposure to beta-xyloside, used as a false "core protein," resulted in marked enhancement of GAG chain formation, suggesting that the synthesis of the sulfated carbohydrate chain itself was not rate limiting. Proteoglycan synthesis and secretion were stimulated by several types of connective tissue activating peptides (CTAP); CTAP-III stimulation of incremental core protein and glycosaminoglycan was shown to be of a similar magnitude. Since chain synthesis was not rate limiting, it is suggested that stimulated proteoglycan formation caused by the CTAP peptides may be primarily modulated through increased formation of core protein.
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1 The nature of an aerosol and the techniques that have been used to obtain altered states of consciousness by deliberately inhaling the contents are described. 2 The development of the phenomenon, first in the USA, and subsequently in the UK is traced. 3 The consultation between Government Departments and the British Aerosol Manufacturers Association (BAMA) is outlined, and the decisions reached are detailed. 4 Reference is made to the ingredients contained in aerosols which when abused, cause altered states of consciousness and a brief review of their properties is included. 5 The mortality statistics in the UK collected by BAMA are described and analysed in detail and finally the approach of manufacturers to the problem is defined.
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The quantitative radiochemical methodology described in this report allows a major increase in information generation, increased experimental flexibility, improved statistical control, and increased diversity of information per culture. Other advantages relate to economies of technical time, supplies, cells, and test materials per individual culture. Microcultures of human synovial cells incorporate [14C]glucosamine into hyaluronic acid that accumulated primarily in the media and to a lesser extent in the cell mass. CTAP-I (from lymphoid cells), CTAP-III (from human platelets), PGE2, dibutyryl cAMP, and poly(I) . poly(C) markedly stimulated hyaluronate synthesis, whereas cortisol, cycloheximide, and tunicamycin inhibited stimulated synthesis. Time studies with cycloheximide indicated that translation, essential for the activation of synovial cells, was completed by 17 h postexposure to CTAP-I. Tunicamycin also seemed to inhibit CTAP-I induced activation primarily by interfering with translation; however, tunicamycin also caused modest post-translation inhibition of hyaluronate synthesis in activated adult human synovial cells.
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A series of N-substituted 2-aminopyrimidines were prepared and tested for pharmacological activity associated with stimulation of central and peripheral dopamine receptors using piribedil as the reference standard. Most of the new compounds showed some degree of dopaminergic activity although in many cases central activity was not accompanied by peripheral activity and vice versa. Clear relationships between structure and activity were not apparent and none of the new compounds possessed dopamine receptor blocking properties.
The levels of DDT and related compounds in soil samples from an apple orchard have been determined. Extraction of residues was achieved by cyclic steam extraction and by conventional solvent extraction methods allowing comparison of the two methods. Determination of the organochlorine residues present in the extracts was performed by gas-liquid chromatography-electron-capture detection and by carbon skeleton gas chromatograph-mass spectrometry. Excellent agreement between the two determination techniques was achieved. Prior to application of p,p'-DDT, a value of approximately 0.4 ppm was obtained for Delta DDT in the soil. The major component of this total was DDE. After spraying the apple trees with technical grade, p,p'-DDT, Delta DDT for the soil rose to 0.6 ppm. This increase was due to translocation of p,p'-DDT from the trees.
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