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F J Andrews

Publications and source records attributed to F J Andrews.

30 records · Page 2Linked to original sources
PubMed1994

Polymorphonuclear leukocyte infiltration into gastric mucosa after ischemia-reperfusion.

Polymorphonuclear leukocytes (PMN) have been implicated in the pathogenesis of ischemia-reperfusion injury. The objective of this study was to investigate PMN infiltration and distribution within the gastric mucosa of rats subjected to 30 min gastric ischemia followed by reperfusion. Sections of mucosa were stained for PMN using an immunoperoxidase technique, and injury was assessed by quantitative histology. In control animals, there were 4 +/- 2 PMN/mm2 in the superficial and 9 +/- 4 PMN/mm2 in the deep mucosa. This increased significantly to 67 +/- 9 PMN/mm2 (P < 0.05) and 160 +/- 53 PMN/mm2 (P < 0.01) respectively at 15 min of reperfusion. The percentage of these PMN which were extravasated was 83 +/- 4% in the superficial mucosa and 82 +/- 4% in the deep mucosa (P < 0.001 compared with control levels of 0% in superficial and 10% in deep mucosa). Significant PMN infiltration occurred before full expression of mucosal injury and treatment of rats with anti-PMN antisera blocked reperfusion injury (treated 10.7 +/- 1.4% mucosa damaged, controls 33.5 +/- 2.4%; P < 0.001). Treatment with allopurinol (100 mg/kg) significantly reduced the number of infiltrating PMN (superficial 7 +/- 1/mm2, deep 16 +/- 2/mm2; P < 0.01) and the percentage of extravasating PMN (superficial 40 +/- 10%, deep 30 +/- 15%; P < 0.01) while also significantly reducing tissue injury (21.9 +/- 1.9% mucosa damaged, P < 0.01 compared with controls). We conclude that the immunoperoxidase staining provides a simple means of identifying PMN in histological sections. Furthermore, our results support a role for PMN in gastric ischemia-reperfusion injury.

Animals↗
PubMed1994

Effect of nonsteroidal anti-inflammatory drugs on LFA-1 and ICAM-1 expression in gastric mucosa.

Leukocyte adhesion to the endothelium appears to play an important role in gastric injury. This study aimed to develop immunohistochemical staining techniques to investigate the distribution and sequence of expression of both leukocyte [lymphocyte function associated antigen 1 (LFA-1)] and endothelial [intracellular adhesion molecule 1 (ICAM-1)] adhesion molecules in the mucosa after treatment with nonsteroidal anti-inflammatory drugs (NSAIDs). In control rats there were 803 +/- 72 LFA-1-stained cells/mm2 in the deep mucosa, 134 +/- 32 cells/mm2 in the superficial mucosa, and 6.4 +/- 1.2 ICAM-1-stained blood vessels/mm2 in the total mucosa. The number of ICAM-1-stained blood vessels in the mucosa increased significantly after 30 min of treatment with intragastric aspirin (30 mM; 25.2 +/- 7.2/mm2, P < 0.01) and indomethacin (20 mg/kg; 20.7 +/- 4.4/mm2, P < 0.01) before any appreciable mucosal damage was evident. This increase was reversed by treatment with misoprostol (100 micrograms/kg) in both aspirin- (7.6 +/- 1.7/mm2, P < 0.01) and indomethacin-treated animals (10.7 +/- 2.6/mm2, P < 0.05). There was no significant increase in LFA-1-positive cells until 60 min of NSAID treatment. We conclude that the adhesion molecules LFA-1 and ICAM-1 are expressed in the normal gastric mucosa and that the number of ICAM-1-stained blood vessels increase rapidly after NSAID treatment. This increase in ICAM-1 expression may be associated with an inhibition of prostaglandin synthesis by NSAIDs. These results provide further support for the role of early vascular changes in NSAID gastropathy.

Animals↗
PubMed1992

Sequence of gastric mucosal injury following ischemia and reperfusion. Role of reactive oxygen metabolites.

The mechanisms of gastric mucosal injury following a period of ischemia remain unclear. The aim of this study was to determine the relative contributions of ischemia, reperfusion, and reactive oxygen metabolites to mucosal injury induced by temporary occlusion of the celiac artery. Rats were subjected to 30 min of gastric ischemia in the presence of 100 mM HCl. Reperfusion periods ranged from 1 min to 24 hr. Drug treatments included allopurinol (100 mg/kg) or a combination of superoxide dismutase (15,000 units/kg), catalase (90,000 units/kg), and desferrioxamine (50 mg/kg). Mucosal injury was assessed by quantitative histology and the extent of macroscopic hemorrhage. Approximately one third of the total injury to the volume of the mucosa (11.8 +/- 9.1%) was due to ischemia alone. Another third was blocked by allopurinol or superoxide dismutase, catalase, and desferrioxamine (22.1 +/- 6.9%, P less than 0.001; and 25.9 +/- 4.6%, P less than 0.01), respectively, compared with control (32.5 +/- 5.1%). In contrast, extensive surface mucosal injury (62.2 +/- 27.6%) occurred primarily during ischemia and was not affected by antioxidants. Macroscopic hemorrhage was halved by treatment with allopurinol (17.5 +/- 12.6%, P less than 0.01) or superoxide dismutase, catalase, and desferrioxamine (15.9 +/- 14.5%, P less than 0.01). We conclude that temporary celiac occlusion results in gastric mucosal damage that consists of both ischemic and reperfusion components. The majority of surface mucosal injury occurred during ischemia, whereas injury to the volume of the mucosa and the vasculature occurred equally during reperfusion and was associated with reactive oxygen metabolites.

Allopurinol↗
PubMed1992

Misoprostol hepatoprotection against ischemia-reperfusion-induced liver injury in the rat.

The hepatoprotective effects of misoprostol, a PGE1 analog, against ischemia-reperfusion liver injury were studied using a rat partial liver ischemia model. Serum ornithine carbamoyltransferase (OCT) and alanine aminotransferase (ALT) levels were determined as biochemical indices of injury. Hepatic cell necrosis was assessed histologically using tetranitroblue tetrazolium (TNBT) and hematoxylin and eosin (H&E) staining. With placebo treatment, 90 min of partial hepatic ischemia followed by 24 hr of reperfusion resulted in increased levels of serum OCT (760 +/- 521 IU/liter) and ALT (4327 +/- 1982 IU/liter), while extensive hepatic necrosis was evident by TNBT and H&E staining. Treatment with two doses of 25 micrograms misoprostol/kg body weight at 1 min before ischemia and 1 min before reperfusion significantly reduced the serum levels of OCT and ALT (207 +/- 189 IU/liter, P less than 0.01 and 2075 +/- 1217 IU/liter, P less than 0.01, respectively) and hepatic necrosis. When a single dose of misoprostol was administered 1 min before reperfusion, similar protective effects were observed. However, when the treatment of misoprostol was delayed to 1 min after reperfusion, significantly less hepatoprotection was seen. Misoprostol exerted no hepatoprotection at all when it was administered at 5 min or later after reperfusion. These results demonstrate that misoprostol partially protects the liver against ischemia-reperfusion injury in the rat. The observation that the protective effect of misoprostol occurs only within the first minute of reperfusion suggests that its mechanism of action involves an early event in reperfusion injury, such as modifying the effects of reactive oxygen metabolites.

Animals↗
PubMed1991

Indomethacin inhibits the chemical carcinogen benzo(a)pyrene but not dimethylbenz(a)anthracene from altering Langerhans cell distribution and morphology.

Treatment of murine skin with the polyaromatic hydrocarbon carcinogens benzo(a)pyrene (BP) or dimethylbenz(a)anthracene (DMBA) for 3 weeks resulted in an increase and a decrease in epidermal Langerhans cell (LC) numbers, respectively, compared with solvent-treated skin. Implantation of subcutaneous indomethacin pellets prior to carcinogen treatment prevented the changes in LC numbers and morphology in BP, but not DMBA-treated skin. Indomethacin treatment was also found to reduce elevated prostaglandin E2 (PGE)2 levels in the skin of BP-treated mice, whereas PGE2 levels were not significantly raised in DMBA-treated mice. There thus appears to be a link between altered prostaglandin levels and LC numbers in murine skin treated with BP, but not DMBA. In the latter, LC numbers were reduced by mechanisms not reversed by indomethacin. It is concluded that increased prostaglandin levels may contribute to the impairment of cutaneous immunity previously observed in BP-treated mice by altering LC density and morphology within the epidermis.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1987

Effect of nutritional iron deficiency on acute and chronic inflammation.

Mild nutritional iron deficiency significantly reduced the severity of adjuvant induced joint inflammation assessed by histology, microfocal radiography, and subjective scoring. Other indices of adjuvant induced inflammation, such as increased levels of serum acute phase reactants, characteristic pathological changes in the inguinal lymph nodes, and granuloma formation at the site of adjuvant injection, were not different from those of control animals. The level of iron deficiency used did not affect the acute inflammatory response to a range of irritants and was not sufficient to suppress immune function. Both the hypersensitivity reaction to oxazalone and lymphocyte tritiated thymidine incorporation were normal. These observations support the view that iron has a selective influence on joint mediated inflammation.

Acute-Phase Proteins↗
PubMed1987

Effect of iron chelation on inflammatory joint disease.

Mild iron deficiency induced by treatment with the iron chelator desferrioxamine reduced the incidence and severity of joint inflammation associated with adjuvant disease in rats but did not alter the local primary inflammatory response or the systemic sequelae. Both rats treated with desferrioxamine and control rats showed increased levels of alpha 1 acid glycoprotein, characteristic pathological changes in the liver and inguinal lymph nodes, and the primary inflammatory response at the site of injection. Histology, microfocal radiography, and gross assessment of the joints, however, showed a suppression or reduction in soft tissue swelling and bone erosion in the rats treated with desferrioxamine. This is a novel observation suggesting an apparently selective influence of iron on joint mediated inflammation.

Animals↗
PubMed1986

Is chronic synovitis an example of reperfusion injury?

In an attempt to define why the joint synovial cavity is prone to develop persistent synovial inflammation we show that hypoxia is induced by pressure changes caused by exercise in the presence of an inflammatory effusion. On resting 'reperfusion injury' may take place. The biochemistry of reperfusion injury has only recently been defined and perhaps surprisingly for an insult that has hypoxia as its central ingredient involves the subsequent production of oxygen derived free radical species. We apply the reaction sequences that are believed to occur during hypoxic/reperfusion injury to the joint synovial cavity and, on the basis of reported 'in vivo' observations, suggest novel therapeutic approaches that we believe are applicable to the treatment of persistent synovial inflammation.

Animals↗
PubMed1978

Cervical cancer in younger women.

Cervical cancer does not begin in women at some vague mid-procreative term, but is a concomitant of early sexual activity. In Brighton the mean age of patients with histologically proven carcinoma of the cervix has been falling, from 50 in 1967 to 35 by 1977. In one year abnormal cells were found in cervical smears from 24 teenage girls (5 aged 16, 2 aged 17, 8 aged 18 and 9 aged 19), and in 4 of these teenage cases malignancy was subsequently proved histologically. Until the aetiology of the disease is established no lower age limit should be set for cervical screening; all young women should be entitled and encouraged to have cervical cytology tests.

Adenocarcinoma↗
PubMedDate not supplied

The role of luminal factors in prostaglandin protection against ethanol-induced gastric mucosal injury.

Prostaglandins (PG) protect the gastric mucosa against damage by several irritants, but the mechanisms remain unclear. A standard rat model of gastric injury induced by 50% ethanol was used to test the hypothesis that PG protection occurs either by increasing luminal fluid volume and hence diluting the irritant, or by production of protective factors within this fluid. Quantitative histology was used to assess microscopic mucosal damage. The increase in luminal fluid volume in prostaglandin E2 (PGE2)-treated animals was measured, and the ability of this increased fluid to protect saline-treated animals via dilution of the irritant was assessed. The transfer of protection by exchange of luminal fluid from PG to non-PG treated animals was also tested. Results showed that PGE2 induced a specific increase in luminal fluid volume of 45.6%. When given together with ethanol treatment the extra fluid volume was not protective. Removal of luminal fluid after PG and before ethanol treatment did not abolish protection and no protective factor was transferred with the luminal fluid. In conclusion, this study has shown that neither dilution of ethanol by accumulation of luminal fluid nor the presence of luminal factors is responsible for PG protection.

Animals↗
PubMedDate not supplied

Sulphated macromolecules produced by in vivo labelling in the rat gastric mucosa.

The aim of this study was to investigate the nature and distribution of sulphated macromolecules of the extracellular matrix in rat gastric mucosa. This was achieved by developing an in vivo labelling system. An intraperitoneal injection of 1 mCi [35S]-sulphate was given for either 4 h (0.01% incorporation into macromolecular fraction) or 8 h (0.13% incorporation). At the end of the labelling period the stomach was removed and the mucosa and submucosa was either taken as a single combined sample or separated into four layers by blunt dissection. Each sample was papain digested and analysed by ion-exchange chromatography. This analysis revealed sulphated species of differing charge existing in differing proportions throughout the mucosa. These sulphated species eluted at NaCl concentrations of approximately 0 (A), 0.19 (B), 0.34 (C) and 0.78 mol/L (D) from a Q-Sepharose ion exchange column. Further analysis by size exclusion chromatography and chemical and enzymatic digestion showed that peaks B and C had molecular weights of 2.4 x 10(5) and 2.8 x 10(5), respectively and were resistant to chondroitinase ABC, heparitinase and nitrous acid digestion. Peak D was found to contain a polydisperse population of molecules with a molecular weight range of approximately 1 x 10(4) to 6 x 10(4). This sample was susceptible to nitrous acid and chondroitinase ABC digestion and was found predominantly in the sample isolated from deeper in the tissue. We have thus developed an in vivo labelling technique for sulphated macromolecules that can be used in the further study of injury to the gastric mucosa.

Animals↗