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  • 1
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 165 (1950), S. 234-234 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] I would like to point out that when the Wakefield Mission was officially instructed before proceeding to Africa in June 1946, we were told, if the plan for the mechanized production of groundnuts presented to us was found to be feasible, to prepare a schedule for the production of not less than ...
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Alimentary pharmacology & therapeutics 9 (1995), S. 0 
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background: In indomethacin-induced jejunal ulceration in the rat, villi undergo both early microvascular injury and shortening that may involve activation of villous smooth muscle. Aim: This study sought to substantiate light microscopic observations using three-dimensional imaging of early villous architectural changes in response to indomethacin. Methods: At both 2 and 6 h after oral indomethacin 15 mg/kg or vehicle to groups of rats, the vasculature of the small intestine was visualised by both carbon-ink perfusion/confocal microscopy and injection casting. The mucosa was also examined for lesions by dissection microscopy and scanning electron microscopy. Results: In indomethacin-dosed rats examined by scanning electron microscopy and histology, the mucosa at 2 h showed villous shortening and wrinkling of the surface epithelium without epithelial loss: at 6 h, the mucosa was flattened, often with epithelial loss to expose a ‘contracted’ villous core. Examination of the vasculature in carbon-injected tissues indicated significant reductions of both mucosal height and inter-capillary distance at both 2 and 6 h post-indomethacin. Scanning electron microscopy of injection casts at 2 and 6 h indicated similar changes. These changes were not seen in control tissues. Conclusion: Histology, confocal microscopy and scanning electron microscopy support the proposal that villous shortening with disruption of surface capillary architecture are early changes in the ulcerative enteropathy induced by nonsteroidal anti-inflammatory drugs.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The early histological features of indomethacin-induced jejunal injury in the rat are described in tissues preserved by perfusion-fixation with 10% formolsaline. After an oral dose of indomethacin (15 mg/kg, known to cause severe multifocal ulceration of the rat jejunum), groups of rats were anaesthetized with subsequent perfusion-fixation of the gastrointestinal tract at 1, 2, 3, 6 and 48 h after dosing. Using routine light microscopic techniques, we have observed a sequence of four distinct stages, in time, of small intestinal injury. The earliest histological features were shortening of the villi, epithelial stratification, basal lamina degeneration, eosinophil degranulation and infiltration of the epithelium prior to infiltration of the mucosa by neutrophils. We consider that these earliest changes, seen at 1, 2 and 3 h, represent a distinct histological entity termed Type 1 change or villous ‘tufting’. Type 2 change includes all of the features of Type 1 change plus the subsequent infiltration of the mucosa by neutrophils at 2, 3 and 6 h. Type 3 change includes necrosis of the upper-third of the villi and was mainly seen at 3 and 6 h. Type 4 change describes extreme injury to more than one-third of the mucosa with severe, acute inflammation and perforation of the bowel wall by 48 h. Although a small number of neutrophils had appeared to infiltrate the mucosa as early as 2 h after dosing, they were only significantly increased at 3, 6 and 48 h. Possible pathogenic mechanisms involved in shortening of villi as a result of smooth muscle contraction and the role of mucosal eosinophils in NSAID-induced jejunal injury in the rat are discussed.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Alimentary pharmacology & therapeutics 5 (1991), S. 0 
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The importance of leucocyte–endothelial cell interactions in the inflammatory process is now recognized. In Crohn's disease, we have proposed that these interactions mediate not only the development of the parenchymal cell infiltrate, but also initiate a process (multifocal gastrointestinal infarction) that leads to ischaemic damage to the bowel wall. We review data on the actions of drugs in the treatment of Crohn's disease and, where known, we highlight their effects on leucocyte adhesion to the endothelium. Corticosteroids inhibit adhesion by inhibiting production of interleukin-1, tumour necrosis factor, interferon gamma, leukotrienes and platelet activating factor. Drugs liberating 5-aminosalicylate inhibit leukotriene production. Cyclosporin inhibits T-cell activation, and amplification of the immune response. Inhibition of leucocyte–endothelial cell interactions probably accounts for some of the beneficial effects of these drugs in Crohn's disease.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Alimentary pharmacology & therapeutics 8 (1994), S. 0 
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Aim: We investigated the effect of dexamethasone on indomethacin-induced ulceration in the rat. Methods: Groups of four rats received oral indomethacin (15 mg/kg) and the jejunal mucosa was examined 24 h later for mucosal ulceration. Three of the groups received oral dexamethasone (1,3 and 6 mg/kg) 0.5 h prior to indomethacin, while the fourth received vehicle. Haematological evaluation was performed and ulcers were assessed both histologically and immunohistochemically. Results: Indomethacin caused multifocal jejunal ulceration that was reduced only by the highest dose of dexamethasone (6 mg/kg). Indomethacin caused a significant fall in the blood haemoglobin concentration that was prevented by dexamethasone at all doses. The ulcers induced by indomethacin alone were deep, punched-out and haemorrhagic while the ulcers arising in rats pre-treated with dexamethasone (all doses) were‘plugged‘ by a white fibrino-purulent exudate. Histologically, the dexamethasone ulcer exudate was composed of bacteria, fibrin, mucus and a significant increase in the numbers of neutrophils. Dexamethasone alone had no significant pathological effect on the small intestine. Conclusions: We report the observation that examethasone at high doses inhibits indomethacin-induced jejunal ulceration in the rat while at low doses it promotes‘plugging‘ of ulcers with bacteria, fibrin, mucus and neutrophils that probably reduces haemorrhage from the ulcer base.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Alimentary pharmacology & therapeutics 8 (1994), S. 0 
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background: Patients on nonsteroidal antiinflammatory drugs can develop curious intestinal fibrotic diaphragms.Methods: Groups of rats received indomethacin mixed into a powdered diet at 3 mg.kg/day for 6 and 12 weeks and 6 mg. kg/day for up to 6 weeks. In an attempt to reproduce a human dosing regimen, another group of rats, for a total of 30 weeks, received consecutive periods of indomethacin at 3 mg. kg/day for 12 weeks, 4.5 mg.kg/day for 1 week, 6 mg.kg/day for 1 week, control diet for 6 weeks, 4.5 mg.kg/day for 2 weeks and finally, a control diet for a healing period of 8 weeks. Control rats received powdered diet alone. At termination, the small and large intestines were examined macroscopically and histologically.Results: Indomethacin caused microcytic anaemia, hypoalbuminaemia, small intestinal ulceration, caecal ulceration and inconspicuous raised mucosal lesions in the caecum that histologically showed submucosal fibrosis with disruption and thickening of the apical muscularis mucosae. No control rats showed any abnormality.Conclusion: These fibrotic lesions of the rat caecum resemble human diaphragms and may arise from healed caecal ulcers.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background: The cyclo-oxygenase inhibitor indomethacin induces a pattern of gastrointestinal injury in the rat that is site-dependent. This study compared the extent of injury to different regions of the rat intestine (small intestine, caecum and colon) with the corresponding changes in arachidonic acid metabolism in these areas, following long-term, low-dose indomethachin. Methods: Rats (eight per group) received either indomethacin (3 mg.kg/day) or control diet for either 6 or 12 weeks. At termination animals were bled, examined both macroscopically and microscopically for ulcers, and assayed for blood thromboxane B2, intestinal tissue prostaglandin E2 content and production of leukotriene B4. In a further eight animals luminal indomethacin concentrations from the small intestine, caecum and colon were measured following 6 weeks of chronic drug ingestion. Results: At 6 weeks, macroscopic ulcers were observed in 2/8 (small intestine), 3/8 (caecum) and 1/8 (colon) animals. The corresponding ratios at 12 weeks were 5/8, 8/8 and 0/8. In control animals, a site-dependent gradient of the prostaglandin E2 concentration was found. In indomethacin-dosed animals the intestinal prostaglandin E2 content was reduced significantly in the caecum at 6 weeks, and in all tissues at 12 weeks. An increased leukotriene B4 production was observed in the caecum only, at 12 weeks (P 〈 0.01), and the blood thromboxane B2 was reduced at both time points (P 〈 0.05). Conclusion: There is a site-dependent gradient of the prostaglandin E2 concentration in the rat intestine. The rat caecum is particularly sensitive to long-term low-dose indomethacin, both in terms of chronic intestinal inflammation and changes in prostanoid metabolism. This site-dependent degree of injury may be associated with a local cyclo-oxygenase inhibition.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Oxford UK : Blackwell Science Ltd.
    Alimentary pharmacology & therapeutics 16 (2002), S. 0 
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: There is growing awareness that primary gastrointestinal pathology may play an important role in the inception and clinical expression of some childhood developmental disorders, including autism. In addition to frequent gastrointestinal symptoms, children with autism often manifest complex biochemical and immunological abnormalities. The gut–brain axis is central to certain encephalopathies of extra-cranial origin, hepatic encephalopathy being the best characterized.Commonalities in the clinical characteristics of hepatic encephalopathy and a form of autism associated with developmental regression in an apparently previously normal child, accompanied by immune-mediated gastrointestinal pathology, have led to the proposal that there may be analogous mechanisms of toxic encephalopathy in patients with liver failure and some children with autism. Aberrations in opioid biochemistry are common to these two conditions, and there is evidence that opioid peptides may mediate certain aspects of the respective syndromes. The generation of plausible and testable hypotheses in this area may help to identify new treatment options in encephalopathies of extra-cranial origin.Therapeutic targets for this autistic phenotype may include: modification of diet and entero-colonic microbial milieu in order to reduce toxin substrates, improve nutritional status and modify mucosal immunity; anti-inflammatory/immunomodulatory therapy; and specific treatment of dysmotility, focusing, for example, on the pharmacology of local opioid activity in the gut.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Copenhagen : Munksgaard International Publishers
    Allergy 55 (2000), S. 0 
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background: Patterns of neonatal exposure to microorganisms have changed substantially over the last 100 years, and it has been suggested that this has influenced the risk of immune-mediated disease. Using a proxy measure, we tested the hypothesis that the initial handling of newborn infants, which is known to affect the pattern of exposure to microorganisms, may alter the risk of developing subsequent atopy, as indicated by hay fever. Methods: Analysis was performed on 5519 members of the 1970 British Cohort Study, a nationally representative birth cohort. Cohort members with hay fever were identified at intervals up to the age of 26 years. Details of neonatal care and childhood circumstances were recorded prospectively. Those who had spent their first night away from their mother in the communal infant nursery were selected as likely to have experienced atypical exposure compared with infants who remained with their mother. Adjustment was made for potential confounding factors in infancy and childhood by multiple logistic regression analysis. Results: Unadjusted relative odds (with 95% CI) for developing hay fever among those spending the first night in the communal nursery, when compared with other infants who remained with the mother, were 1.48 (1.23–1.77), P〈0.001. Comprehensive adjustment for the potential confounding factors, including feeding practices on the first day of life, markers of social and material circumstances, and region, did not substantially alter this relationship, with adjusted relative odds of 1.31 (1.08–1.59), P=0.005. Conclusions: While our proxy measure is associated with an increased risk of hay fever, further research is required to confirm that this is due to the pattern of infectious exposure in very early life. The results are consistent with the hypothesis that the first challenges are particularly important in the development of the newborn infant's immune system.
    Type of Medium: Electronic Resource
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  • 10
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    London : Periodicals Archive Online (PAO)
    RSA Journal. 96:4770 (1948:June 4) 386 
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