The chemistry of aluminium in the gastrointestinal lumen and its uptake and absorption.
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Aluminum↗
Biomedical subjects
R P Thompson
Publications and source records attributed to R P Thompson.
A randomized controlled study of evening primrose oil and fish oil in ulcerative colitis.
In a placebo-controlled study, 43 patients with stable ulcerative colitis were randomized to receive either MaxEPA (n = 16), super evening primrose oil (n = 19), or olive oil as placebo (n = 8) for 6 months, in addition to their usual treatment. Treatment with MaxEPA increased red-cell membrane concentrations of eicosapentaenoic acid (EPA) at 3 months by three-fold and at 6 months by four-fold (both P < 0.01), and doubled docosahexaenoic acid (DHA) levels at 6 months (P < 0.05). Treatment with super evening primrose oil increased red-cell membrane concentrations of dihomogamma-linolenic acid (DGLA) by 40% at 6 months (P < 0.05), whilst treatment with placebo reduced levels of DGLA and DHA at 6 months (both P < 0.05). Clinical outcome was assessed by patient diary cards, sigmoidoscopy and histology of rectal biopsy specimens. Super evening primrose oil significantly improved stool consistency compared to MaxEPA and placebo at 6 months, and this difference was maintained 3 months after treatment was discontinued (P < 0.05). There was however, no difference in stool frequency, rectal bleeding, disease relapse, sigmoidoscopic appearance or rectal histology in the three treatment groups. Despite manipulation of cell-membrane fatty acids, fish oils do not exert a therapeutic effect in ulcerative colitis, while evening primrose oil may be of some benefit.
Aged↗
Review article: the mode of action of the aminosalicylates in inflammatory bowel disease.
Sulphasalazine and other 5-aminosalicylic acid (5-ASA)-containing drugs are used in the treatment of acute inflammatory bowel disease and in the maintenance of clinical remission. Despite their use for over 50 years, the mechanism of action of this class of drugs remains uncertain, although a number of possibilities are discussed in this review. It seems likely that the aminosalicylates are important free radical scavengers, can reduce leukotriene production and can inhibit the cellular release of interleukin-1, all of which are likely to be important in reducing the acute inflammatory response in inflammatory bowel disease. The effects of these drugs on prostaglandin production are more contentious, but it appears that 10(-5) to 10(-4) M concentrations stimulate production of prostaglandins which may be cytoprotective, while higher doses of these drugs inhibit prostaglandin production. The aminosalicylates may maintain remission in inflammatory bowel disease by preventing leucocyte recruitment into the bowel wall. The drugs inhibit the chemotactic response to leukotriene B4, reduce the synthesis of platelet activating factor and also inhibit leucocyte adhesion molecule upregulation.
Aminosalicylic Acids↗
Angioendotheliomatosis associated with Castleman's lymphoma and POEMS syndrome.
Castleman's lymphoma, a benign localized lymphoid hyperplasia, has been reported in association with POEMS syndrome, a multisystem reactive disorder that includes several skin manifestations. Benign reactive angioendotheliomatosis is a rare skin disorder that is associated with various systemic disorders. A patient with long-standing Castleman's lymphoma and POEMS syndrome also developed benign reactive angioendotheliomatosis.
Adult↗
Inhibition of leucocyte adhesion molecule upregulation by tumor necrosis factor alpha: a novel mechanism of action of sulphasalazine.
The effects of the cytokine tumour necrosis factor alpha and the calcium ionophore A23187 upon CD11a, CD11b, CD11c and CD18 leucocyte membrane expression was analysed in whole blood using monoclonal antibodies and flow cytometry. Both agents significantly increased the density of CD11b/CD18 membrane expression on monocytes and granulocytes, but had no effects on adhesion molecule expression on lymphocytes. The effects of sulphasalazine, 5-aminosalicylic acid (5-ASA) and sulphapyridine upon adhesion molecule upregulation were then examined; 10(-3) and 10(-4) M sulphasalazine and 5-ASA significantly reduced tumour necrosis factor alpha induced CD11b/CD18 upregulation on monocytes and granulocytes but had no effects upon A23187 mediated upregulation. Sulphapyridine was inactive. These results suggest that sulphasalazine and 5-ASA may interfere with mechanisms of leucocyte recruitment in inflammatory bowel disease.
Adult↗
Does the fatty acid profile of dietary fat influence its trophic effect on the small intestinal mucosa?
To compare the enterotrophic effects of different triglycerides, five groups of eight rats were fed mixed diets giving 50% of calories as oils rich in either essential fatty acids (EFA), alpha-linolenic acid, fully saturated fatty acids, oleic acid, or medium chain fatty acids. After 21-24 days there were no significant differences between the groups in overall small intestinal whole gut weight, mucosal weight, or mucosal DNA; overall mucosal protein showed slight variation (p < 0.05) that was compatible with differences in food intake between the groups. However, long chain triglycerides (LCT) and medium chain triglycerides (MCT) differed in their regional effects on cell proliferation; all four LCT rich diets increased mucosal mass and cell proliferation maximally in the mid small intestine, while MCT had their greatest effect proximally. Subsequently, two groups of eight rats were fed diets in which EFA or MCT were given as twice daily boluses (29% of dietary calories) for 20 to 23 days and compared with a third group of eight rats receiving a glucose rich, low fat diet. EFA and MCT boluses increased the overall parameters of small intestinal mucosal mass and for both oils the effects were now maximal in the mid small intestine. Thus different triglycerides have similar effects on overall small intestinal mucosal mass, but MCT differ from LCT in their regional effects on mucosal cell proliferation when they are given in mixed diets, although not when given as boluses.
Animals↗
Evidence for a distinct gap-junctional phenotype in ventricular conduction tissues of the developing and mature avian heart.
The gap-junctional proteins connexin43 and connexin42 have been shown to be expressed in the developing and mature avian heart, but their respective spatiotemporal distributions are unknown. In the present study, we have immunolocalized connexin42 in the conduction tissues of the adult avian heart (nonbranching bundle, bundle branches, and Purkinje fibers) and vascular endothelial cells. Connexin43 immunolabeling was confined to vascular smooth muscle. A novel microwave-based method was used to label connexin42 and connexin43 in the same tissue section. Neither connexin42 nor connexin43 was immunolocalized in working myocardium, atrioventricular node, and atrioventricular ring tissue of the bird heart. Although connexin42 first appeared in periarterial conduction myocytes and vascular endothelium at 9-10 embryonic days, the central conduction tissues, including the nonbranching bundle and proximal branches, remained immunonegative for connexin42 up until hatching (approximately 20 embryonic days). During the early postnatal period (1-14 days), connexin42 immunolabeling progressively spread up the bundle branches toward the nonbranching bundle. Connexin42 appeared uniformly distributed along the left bundle branch by 14 postnatal days. The distribution and spread of connexin42 immunoreactivity suggest that the emergence of specialized junctional contacts along ventricular fascicles occurs relatively late in heart development and coincides with the emergence of the chick from incubation within the egg.
Age Factors↗
Amaurosis fugax, Crohn's disease and the anticardiolipin antibody.
Crohn's disease is associated with a hypercoagulable state due to platelet or clotting abnormalities which may be responsible for the thromboembolic episodes seen in this condition. We report the occurrence of anticardiolipin antibodies in a patient with Crohn's disease who presented with Amaurosis fugax and suggest that these antibodies may be a further cause of the hypercoagulable state of Crohn's disease in some patients.
Aged↗
The spatial distribution and relative abundance of gap-junctional connexin40 and connexin43 correlate to functional properties of components of the cardiac atrioventricular conduction system.
Electrical coupling between heart muscle cells is mediated by specialised regions of sarcolemmal interaction termed gap junctions. In previous work, we have demonstrated that connexin42, a recently identified gap-junctional protein, is present in the specialised conduction tissues of the avian heart. In the present study, the spatial distribution of the mammalian homologue of this protein, connexin40, was examined using immunofluorescence, confocal scanning laser microscopy and quantitative digital image analysis in order to determine whether a parallel distribution occurs in rat. Connexin40 was detected by immunofluorescence in all main components of the atrioventricular conduction system including the atrioventricular node, atrioventricular bundle, and Purkinje fibres. Quantitation revealed that levels of connexin40 immunofluorescence increased along the axis of atrioventricular conduction, rising over 10-fold between atrioventricular node and atrioventricular bundle and a further 10-fold between atrioventricular bundle and Purkinje fibres. Connexin40 and connexin43, the principal gap-junctional protein of the mammalian heart, were co-localised within atrioventricular nodal tissues and Purkinje fibres. By applying a novel photobleach/double-labelling protocol, it was demonstrated that connexin40 and connexin43 are co-localised in precisely the same Purkinje fibre myocytes. A model, integrating data on the spatial distribution and relative abundance of connexin40 and connexin43 in the heart, proposes how myocyte-type-specific patterns of connexin isform expression account for the electrical continuity of cardiac atrioventricular conduction.
Animals↗
Sartorius myoplasty in the treatment of exposed arterial grafts.
The long-term success of sartorius myoplasty in 14 of 16 patients who presented with an exposed vascular graft in an infected groin is described. The presenting complications were wound dehiscence (ten patients), hemorrhage (two), skin erosion (two), late bilateral fistulas (one) and false aneurysm (one). Ten grafts were prosthetic and six autogenous. Positive cultures were obtained from 15 wounds; four grew Staphylococcus epidermidis, the remainder mixed or Gram-negative bacteria. Each groin was radically debrided, including the surface of the arterial graft, and, if possible, closed immediately with a sartorius myoplasty applied directly to the graft. Twist, fan and loop myoplasties were equally effective. Grossly infected wounds were debrided initially and obviously infected grafts were replaced in situ before myoplasty. Sartorius myoplasty is recommended as an elegant solution for the infected groin in which there is an exposed arterial graft.
Adult↗
Automated spectrophotometric method for determining oxidized and reduced glutathione in liver.
An enzymatic recycling method has been applied to the measurement of total and oxidized glutathione with a centrifugal analyzer. When the reduced form of glutathione (GSH) was masked with 2-vinylpyridine to measure the oxidized glutathione (GSSG), the time to ensure full derivatization was three times longer than has been reported. The method is quick, simple, accurate, and precise (1.27% for GSH, 3.3% for GSSG intraassay CV; 2.15% for GSH, 5% for GSSG interassay CV), and the automation allows large numbers of samples to be conveniently assayed.
Autoanalysis↗
The effects of sulphasalazine and its metabolites on prostaglandin production by human mononuclear cells.
Although it has been proposed that sulphasalazine (SASP) and its metabolite 5-aminosalicylic acid (5-ASA) act therapeutically by inhibiting production of vasoactive and immunoregulatory prostaglandins (PGs), in previous in vitro studies these drugs have both inhibited and promoted PG production. This study demonstrates that SASP and 5-ASA promote or inhibit peripheral blood mononuclear cell PG production depending upon the PG measured, the concentration of the drug, and whether the cells were stimulated. Sulphapyridine, the other constituent of SASP, only inhibited production. At high concentrations of SASP and 5-ASA the viability of mononuclear cells was reduced. The enhancement of PG production and toxicity was greater with SASP than 5-ASA, while the PGs most affected by SASP were not those most affected by 5-ASA. Thus, in vitro SASP may possess properties other than those of 5-ASA and this may explain the different therapeutic properties of these two compounds.
Aminosalicylic Acids↗
Distribution of the novel developmentally-regulated protein EAP-300 in the embryonic chick nervous system.
In a previous study we described a 300 kDa, developmentally regulated protein identified in embryonic chick neural retina with a monoclonal antibody. Because this protein has been shown to be undetectable in the adult nervous system, and the monoclonal antibody is species-specific, the protein has been named embryonal avian polypeptide of 300 kDa (EAP-300). In the present study we have analyzed the histological expression of EAP-300 during chick embryogenesis. In the developing nervous system, EAP-300 expression was detected as early as Stage 5 (19 h), and was subsequently down-regulated to undetectable levels in the adult. Of particular interest was the association of EAP-300 with putative barriers of neuronal growth, such as the telencephalon/diencephalon glial knot, the dorsal midline in the mesencephalon and the midline in myelencephalon, and the spinal cord roof plate. EAP-300 was also shown to be expressed by Bergmann glia during the period of granule cell migration in the cerebellum. The expression of EAP-300 by radial astrocytes was confirmed in culture by immunofluorescent co-labeling with a MAb to EAP-300 and the R5 MAb, which is a radial astrocyte-specific marker. It has also been shown that EAP-300, when immunopurified from embryonic brain under non-dissociating conditions, co-purifies with a neural keratan sulfate proteoglycan that is also associated with CNS barrier structures during brain development. The restricted expression of EAP-300 in nervous tissue, particularly in CNS barrier structures, suggests that EAP-300 may play an important, but transient, role in the development of the chick nervous system.
Animals↗
Immunolabelling patterns of gap junction connexins in the developing and mature rat heart.
The distribution of gap junctions in prenatal, postnatal, and adult rat hearts was studied by laser scanning confocal microscopy, using antiserum raised to a peptide (HJ) matching part of the sequence of connexin43 (a cardiac gap junction protein). Using digital reconstruction of optically-sectioned tissue volumes, a highly sensitive detection of immunolabelled gap junctions was achieved. The distribution of positive anti-HJ immunolabelling was regionalised in the prenatal heart from its first detection at 10 days post-coitus. High levels of immunopositive staining occurred in the trabeculae of the embryonic ventricles. Other zones of the early myocardium including early central conduction tissues had no detectable signal. The prenatal outflow tract, interventricular septum and a narrow zone of myocardium subjacent to the epicardial free wall also had low levels of immunopositive signal. During postnatal growth and in the adult rat heart, a marked distinction emerged between the central conducting tissues of the atria and ventricles. Whilst small immunostained gap junctions became detectable within the atrioventricular node on the atrial side of the junction, between the interatrial and interventricular septa, no immunolabelling was found within the ventricular branching bundle. This difference between the atrioventricular node and branching bundle is consistent with potential functional distinctions between these two structures, and is not consistent with the recent proposal that the His bundle and its branches act as an extended atrioventricular node in smaller mammals such as the rat. Ventricular Purkinje fibres, distal to the branching bundle, showed high levels of anti-HJ immunostaining. Organisation of gap junctions into intercalated disks within the ventricle proceeded late into intercalated disks within the ventricle proceeded late into the adolescent stages of heart growth. The distribution of a second connexin protein, MP70, not previously characterised in the heart, was studied using monoclonal antibodies. MP70 was transiently immunolabelled in the heart during the postnatal period, but only within valves. Previously, this protein has been reported only in the eye lens. MP70-containing gap junctions may represent a specialisation in avascular tissues, since blood vessels are not present in either the eye lens or the cusps of heart valves.
Animals↗
Expression of adhesion molecules on circulating leucocytes in patients with inflammatory bowel disease.
1. The expression of leucocyte antigens CD11/CD18 and complement receptor 1 was studied on the circulating leucocytes of 13 patients with inflammatory bowel disease and 13 age- and sex-matched healthy control subjects. 2. Monoclonal antibodies against CD11/CD18 and complement receptor 1 were added to leucocyte suspensions from patients and control subjects. Antibody binding was detected using a fluorescein-conjugated rabbit anti-mouse antibody and flow cytometry. The proportions of lymphocytes, monocytes and granulocytes expressing these molecules and the density of antigen expression, measured as mean fluorescence intensity, were determined. 3. There were no differences between patients and control subjects in the mean fluorescence intensity of antibody staining of surface molecules or in the proportion of cells expressing each molecule for any cell type. Analysis of subgroups of patients according to disease type, severity or treatment also showed no difference compared with control subjects. 4. We conclude that failure to identify a population of circulating leucocytes whose adhesion molecules or complement receptors are upregulated may arise because cells are only activated locally within the gut vasculature. Alternatively, structural changes in these molecules, rather than an increase in their number or the expression of other surface glycoproteins, may be more important in mediating adhesive interactions in inflammatory bowel disease.
Adult↗
The effects of 5-aminosalicylic acid and acetyl-5-aminosalicylic acid on lipid peroxidation in erythrocytes and prostaglandin production by mononuclear cells.
In parallel studies, the effects of 5-aminosalicylic acid (5-ASA) and acetyl-5-aminosalicylic acid (acetyl-5-ASA) on peroxidation of red-cell membrane lipids and production of prostaglandins by peripheral blood mononuclear cells were assessed. 5-ASA at concentrations of 10(-5), 10(-4) and 10(-3) M significantly inhibited erythrocyte lipid peroxidation, measured as malondialdehyde production, by 20%, 56% and 63%, respectively, (P < 0.05, P < 0.002, P < 0.001, respectively) while acetyl-5-ASA had no effect. 10(-5) and 10(-4) M 5-ASA significantly increased production by stimulated peripheral blood mononuclear cells of PGE2 (by 31% and 30%, P < 0.01, P < 0.05, respectively) and PGF2 alpha (by 30% and 25%, P < 0.05, P < 0.01, respectively). 10(-4) M 5-ASA also significantly stimulated prostacyclin production measured as 6KF1 alpha by 10% (P < 0.05). At 10(-3) M 5-ASA there were significant falls in 6KF1 alpha (by 37%) PGE2 (by 45%) and PGF2 alpha (by 47%) (P < 0.01, P < 0.001, P < 0.001, respectively) although this was accompanied by a decrease in cell viability. Acetyl-5-ASA had little effect upon prostaglandin production. 5-ASA scavenges free radicals and stimulates production of cytoprotective prostaglandins.
Aminosalicylic Acids↗
Concentrations of metals in gastric juice in health and peptic ulcer disease.
The concentrations of essential metal cations in gastric juice, collected at endoscopy from 17 normal patients and 11 with peptic ulcer disease, were determined by inductively coupled plasma emission spectrometry. Mean fasting levels in normal gastric juice were as follows: sodium 47.7 mM, potassium 14.6 mM, calcium 0.8 mM, magnesium 0.36 mM, zinc 13 microM, and copper 1.2 microM: these did not differ significantly in health or disease. Because samples were contaminated with iron, the concentration of this metal was only estimated (ca 3.5 microM in normal subjects), and this secretion could represent a significant proportion of the daily loss of endogenous iron. The pH of gastric juice predicted the concentrations of magnesium and calcium, but not copper or zinc, in the juice. It is concluded that previously reported values for trace metals in gastric juice have been incorrect and that the very low amounts secreted in the gastric juice will not interfere with the absorption of other trace metals from the diet. In contrast, the concentrations of macroelements in gastric juice may be sufficient to stimulate the absorption of trace metals from the gut.
Calcium↗
Effects of bolus doses of fat on small intestinal structure and on release of gastrin, cholecystokinin, peptide tyrosine-tyrosine, and enteroglucagon.
To investigate the enterotrophic effects of bolus doses of long chain triglycerides, two groups of eight female Wistar rats were fed identical diets with 48.2% total calories as the essential fatty acid rich oil Efamol. To one group the oil was given in twice daily bolus doses by gavage, while for the other group the oil was mixed with the remainder of the feed and thus consumed over 24 hours. The animals were killed after 20 to 22 days. Bolus dosing significantly increased parameters of mucosal mass along the length of the small intestine in association with an increase in two hour accumulation of vincristine arrested metaphases in small intestinal crypts. In a second experiment, four replicate studies were carried out, each involving two groups of 12 rats respectively fed as described above. After 21 days one animal from each group was killed every two hours, providing regular plasma samples over 24 hours for measurement of gastrin, cholecystokinin, peptide tyrosine-tyrosine and enteroglucagon. Bolus dosing markedly enhanced release of peptide tyrosine-tyrosine and enteroglucagon, but not of gastrin or cholecystokinin. Thus, the enhanced enterotrophic effects of bolus doses of long chain triglycerides could be mediated by release of a distally located gut peptide, perhaps enteroglucagon.
Animals↗