Biomedical subjects

T Otamiri

Publications and source records attributed to T Otamiri.

13 recordsLinked to original sources

PubMed1991

Oxygen radicals: their role in selected gastrointestinal disorders.

In this article, the evidence for the involvement of free radicals in some of the gastrointestinal disorders is reviewed. Oxygen radicals are partially reduced oxygen species that include superoxide, and hydroxyl radicals, and hypophthalous acids. Most cells possess numerous antioxidant enzymes and scavengers to protect themselves from these injurious agents; the rate of production of reactive oxygen metabolites may exceed the capacity of the antioxidant defenses thus resulting in tissue damage. The gastrointestinal tract is particularly well endowed with the enzymatic machinery necessary to form large amounts of oxygen radicals. Sources of radicals in the gastrointestinal tract include mucosal xanthine oxidase and NADPH oxidase found in the resident phagocytotic leukocytes (macrophages, neutrophils, eosinophils) of the lamina propria. Other sources of oxygen radicals in the gastrointestinal tract involve ischemia and reperfusion, drug ingestion, diet and radiation therapy. Recent studies have demonstrated the involvement of oxygen radicals following active episodes of small-intestinal ischemia, ulcerative colitis, pancreatitis and gastric ulcer. In contrast to cell antioxidants, control of tissue free radical levels is now pharmacologically feasible and perhaps justified for specific diseases. However, carefully designed and controlled clinical trials are needed.

Enterocolitis, Pseudomembranous↗

PubMed1989

Increased lipid peroxidation in malignant tissues of patients with colorectal cancer.

The authors investigated the level of lipid peroxidation and possible related phenomena in the activation of phospholipase A2 and the infiltration of granulocyte neutrophils in human colorectal cancer tissue samples. Malondialdehyde (an index of lipid peroxidation), phospholipase A2 activity, and myeloperoxidase activity (a marker of granulocyte neutrophils) were found to be increased significantly in cancerous compared with macroscopically normal tissues. They concluded that increased lipid peroxidation, phospholipase A2, and myeloperoxidase activity are associated with human colorectal cancer.

Adult↗

PubMed1989

Role of phospholipase A2 and oxygenated free radicals in mucosal damage after small intestinal ischemia and reperfusion.

The influence of quinacrine, a phospholipase A2 inhibitor, and enzymatic scavengers of active oxygen metabolites (superoxide dismutase and catalase) on ischemic small intestinal mucosal damage has been investigated. In the absence of an inhibitor, ischemia and reperfusion caused increased mucosal permeability to sodium fluorescein, increased N-acetyl-glucosaminidase release from the mucosa into the lumen, increased malondialdehyde content, and increased myeloperoxidase and phospholipase A2 (PLA2) activities in the mucosa. All these effects of ischemia were efficiently inhibited by the PLA2 inhibitor quinacrine. On the other hand, superoxide dismutase together with catalase, even if it totally prevented the increased formation of malondialdehyde, was only able to reduce 50 percent of the increases of the other parameters. These findings indicate that, in addition to free radicals, other factors are involved in the pathogenesis of small intestinal mucosal injury after ischemia and reperfusion. We suggest that one such factor is the activation of PLA2 and the generation of various PLA2-dependent compounds such as arachidonic acid metabolites, lysophosphatidyl choline, and platelet-activating factor.

Acetylglucosaminidase↗

PubMed1989

Phospholipase C-mediated intestinal mucosal damage is ameliorated by quinacrine.

Phospholipase C from Clostridium perfringens, when injected into a closed loop of the rat small intestine in vivo, caused an increase in the activity of intraluminal N-acetyl-beta-glucosaminidase and mucosal permeability to sodium fluorescein, indicating damage to the mucosa. Phospholipase C also caused an influx of granulocytes (neutrophils) into the mucosa, as shown by the myeloperoxidase activity--a granulocyte neutrophil marker, and increased localized lipid peroxidation. Pretreatment of animals with quinacrine, a known inhibitor of phospholipase A2, prevented the increases in the luminal N-acetyl-beta-glucosaminidase activity, mucosal permeability, malondialdehyde and myeloperoxidase activity after deposition of phospholipase C in the gut lumen. It is concluded that phospholipase C might impair the function of the mucosal barrier and increase the permeability of the gut to undesirable molecules and pathogens. Part of its action may be mediated via phospholipase A2 activation since pretreatment with quinacrine afforded protection.

Animals↗

PubMed1989

Ginkgo biloba extract prevents mucosal damage associated with small-intestinal ischaemia.

We have examined how a Ginkgo biloba extract influences the damaging effects of ischaemia in the small-intestinal mucosa. We used a rat experimental model in which a ligated loop of the distal ileum was subjected to ischaemia and revascularization, and the ensuing mucosal damage assessed by lysosomal enzyme release and intestinal permeability measurements. We also determined the mucosal content of malondialdehyde, a lipid peroxidation product, and the mucosal activity of myeloperoxidase, a neutrophil granulocyte marker. Ischaemia and revascularization alone caused increased mucosal permeability to sodium fluorescein, increased N-acetyl-beta-glucosaminidase release from the mucosa into the lumen, increased malondialdehyde content in the mucosa, and increased myeloperoxidase activity in the mucosa. Intravenous injection of G. biloba extract caused a dose-dependent attenuation of all these effects of ischaemia. It is suggested, therefore, that G. biloba extract may protect the intestinal mucosa against ischaemic damage by reducing neutrophil infiltration and lipid peroxidation.

Acetylglucosaminidase↗

PubMed1989

Lipid peroxidation products in postischemic skeletal muscle and after treatment with hyperbaric oxygen.

Earlier studies from our laboratory have shown that hyperbaric oxygen (HBO) treatment reduces edema, enhances aerobic metabolism and improves the recovery of the phosphorylase activity in postischemic rat skeletal muscle. However, as it has become increasingly apparent that oxygen in excess may have harmful effects, it was of interest to study if HBO caused an increased formation of oxygen free radicals. Toxic peroxides, as a result of oxygen free radicals, were quantitated in the postischemic skeletal muscle of rat and with HBO treatment by measuring the thiobarbituric acid reaction which includes the lipid peroxides and the alkydes including malondialdehyde (MDA), a key intermediate in the formation of peroxides. A tourniquet model of temporary ischemia of the rat hindlimb was used for 3 hours. Muscle biopsies were taken at various intervals before and after tourniquet release with and without hyperbaric oxygen at 2.5 atmospheres absolute (ATA) for 45 min after tourniquet release. Three hours of anesthesia caused a significant rise of thiobarbituric acid reactive material (TBAR) concentration in muscle compared to normal controls without anesthesia. An increase of similar magnitude was seen after 3 hours of ischemia, with or without reperfusion. These values were normalized after 45 min. HBO in the postischemic phase did not cause a further increase in the TBAR concentration in muscle immediately postischemically. However, the levels remained increased at 45 min after the onset of reperfusion, immediately after HBO treatment and had returned to normal values 2 hours postischemically.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Oxygen radicals, lipid peroxidation, and neutrophil infiltration after small-intestinal ischemia and reperfusion.

In this study the role of free radicals, lipid peroxidation, and neutrophil infiltration as mediators of ischemia and reperfusion-induced intestinal mucosal damage were investigated. We used a rat experimental model in which a ligated loop of the distal ileum was subjected to ischemia and reperfusion and the ensuing mucosal damage was assessed by means of lysosomal enzyme release and intestinal permeability measurements. We also determined the mucosal content of malondialdehyde, a lipid peroxidation product, and the mucosal activity of myeloperoxidase, a neutrophil granulocyte marker. Ischemia and revascularization alone caused increased mucosal permeability to sodium fluorescein, increased N-acetyl-beta-glucosaminidase release from the mucosa into the lumen, increased malondialdehyde content in the mucosa, and increased myeloperoxidase activity in the mucosa. Intravenous injection of enzymatic antioxidant, superoxide dismutase, together with xanthine oxidase inhibitor, allopurinol, prevented the malondialdehyde accumulation and caused attenuation of all the other effects of ischemia. Intravenous pretreatment of hydrocortisone sodium succinate (Solu-Cortef), a steroid and also a nonenzymatic antioxidant, prevented not only malondialdehyde accumulation but also neutrophil infiltration and mucosal damage. These data support a concept that neutrophil infiltration is an important element in ischemic mucosal damage. In addition, the blocking of this phenomenon may have clinical significance in attempts to modulate the potential damaging effects of the increased neutrophil infiltration associated with small-intestinal ischemia.

Acetylglucosaminidase↗

PubMed1988

Quinacrine prevention of intestinal ischaemic mucosal damage is partly mediated through inhibition of intraluminal phospholipase A2.

The influence of total ischaemia and revascularization on luminal phospholipid metabolism in the rat small intestine was investigated. Two hours of total ischaemia followed by five minutes of revascularization caused increases in phospholipase A2 activity, and lysophosphalidylcholine content in the gut lumen. The above treatment also resulted in mucosal damage expressed as an increase in N-acetyl-beta-glucosaminidase activity in the lumen. Pretreatment of animals with the phospholipase A2 inhibitor, quinacrine prevented the increases in luminal phospholipase A2 activity and mucosal damage following ischaemia and revascularization. Intraluminal injection of either phospholipase A2 purified from snake venom or Triton X-100 resulted in increased activity of N-acetyl-beta-glucosaminidase in the luminal content. Again, quinacrine pretreatment of animals prevented the increases in mucosal permeability and activity of N-acetyl-beta-glucosaminidase after intraluminal injection of purified phospholipase A2. On the other hand quinacrine pretreatment had no influence on the observed effects of Triton X-100 treatment. These findings suggest that an increase in luminal phospholipase A2 could be involved in mediating the mucosal injury caused by small intestinal ischaemia.

Acetylglucosaminidase↗

PubMed1988

Phospholipase A2 inhibition prevents mucosal damage associated with small intestinal ischaemia in rats.

The influence of various inflammatory inhibitors on the damaging effects of ischaemia in the small intestinal mucosa has been investigated. A rat experimental model was used, in which a ligated loop of the distal ileum was subjected to ischaemia and revascularisation and the ensuing mucosal damage assessed by lysosomal enzyme release and intestinal permeability measurements. The mucosal content of malondialdehyde - a lipid peroxidation product - and its activity of myeloperoxidase - a neutrophil granulocyte marker was also determined. In the absence of inhibitor, ischaemia and revascularisation caused increased mucosal permeability to sodium fluorescein, increased N-acetyl-beta-glucosaminidase release from the mucosa into the lumen, increased malondialdehyde content in the mucosa and increased myeloperoxidase activity in the mucosa. All these effects were inhibited by the phospholipase A2 inhibitors, quinacrine and nordihydroguaiaretic acid (NDGA), while the lipoxygenase inhibitor, BW755C, had no influence and the cyclooxygenase inhibitor, indomethacin, potentiated the increases in mucosal permeability and N-acetyl-glucosaminidase release. BN 52021, a specific platelet activating factor antagonist, did not influence the myeloperoxidase activity, but it decreased the formation of malondialdehyde and the increases in mucosal permeability and N-acetyl-beta-glucosaminidase release, although not to the same extent as quinacrine and NDGA. These findings indicate that phospholipase A2 inhibition prevents mucosal damage associated with small intestinal ischaemia and suggest that at least part of the ischaemic damage is mediated by products of phospholipase A2 activity that are not arachidonic acid metabolites.

Acetylglucosaminidase↗

PubMed1987

Increased phospholipase A2 and decreased lysophospholipase activity in the small intestinal mucosa after ischaemia and revascularisation.

The influence of ischaemia and revascularisation on lipid peroxidation and phospholipid metabolism in the rat small intestinal mucosa was investigated. Two hours of total ischaemia followed by five minutes of revascularisation caused not only accumulation of malondialdehyde in the mucosa, but also increased activity of phospholipase A2, decreased activity of lysophospholipase, and increased ratio between lysophosphatidylcholine and phosphatidylcholine. Pretreatment with the phospholipase A2 inhibitor, quinacrine, prevented the increases in mucosal phospholipase A2 activity and lysophosphatidylcholine/phosphatidylcholine ratio after ischaemia and morphological examinations revealed that the mucosa was then also protected against ischaemic injury. These findings point to the possibility that activation of phospholipase A2 and accumulation of lysophosphoglycerides could be involved in mediating the mucosal injury caused by small intestinal ischaemia.

Animals↗

PubMed1987

An experimental model for studying reversible intestinal ischemia.

We have developed a simple experimental model for studying reversible intestinal ischemia. The model is based on tenting the mesenteric vessels (artery and vein) to a tied loop of the small bowel in rat and, after a certain time, lowering them down again. Total and partial ischemia (created by tenting 2 and 1 cm, respectively) were demonstrated by laser Doppler flowmetry, as was the revascularization obtained after bringing the vessels down again. Alterations in mucosal permeability after ischemia were determined by depositing fluorescent dextran 3000 in the tied loop and measuring its concentration in the portal blood, and mucosal damage due to ischemia was assessed by measuring the activity of N-acetyl-beta-glucosaminidase, a lysosomal enzyme, in the gut lumen. There was a significant increase in the intestinal permeability to dextran 3000 after total ischemia for 10 min or more, and the permeability was directly related to the duration of the ischemia. After the intestine had been subjected to total ischemia for 30 min or more, the activity of N-acetyl-beta-glucosaminidase in the luminal contents was significantly increased. The permeability after partial ischemia for 30 min was less than that after total ischemia for 30 min. After total ischemia for 10 min followed by revascularization for 30 or 60 min, the permeability did not differ from that in animals not subjected to ischemia. It is concluded that this simple model may be used to study reversible small intestinal ischemia and factors that influence mucosal permeability.

Acetylglucosaminidase↗

PubMed1987

Intestinal obstruction with strangulation of the small bowel.

The records of 128 patients operated on for adhesive complete mechanical obstruction of the small intestine were retrospectively reviewed. The gut proved to be strangulated in 53 cases, irreversibly in 16 and reversibly in 37, while 75 patients had simple obstruction (12, 29 and 59%). Continuous abdominal pain was more common in strangulation than in simple obstruction and leukocytosis was most common in irreversible strangulation (both differences significant). But no preoperative clinical parameter was specific for strangulation obstruction. Preoperative hospital stay greater than 25 hours was significantly more common in irreversible strangulation obstruction than in the other groups. Strangulation was preoperatively recognized in only 25% of the cases. The overall mortality rate was 5.5%, but with no statistical intergroup difference, possibly because so few patients died. The study showed that strangulation usually is unrecognized preoperatively, and that early operation is essential for obstruction due to intestinal strangulation. Early surgery is therefore indicated in most cases clinically diagnosed as intestinal obstruction.

Adolescent↗

PubMed1986

Lysophosphatidylcholine potentiates the increase in mucosal permeability after small-intestinal ischaemia.

The influence of lysophosphatidylcholine (lysoPC), taurodeoxycholate (TDC), and taurochenodeoxycholate (TCDC) on the permeability properties of the ischaemic small-intestinal mucosa was investigated. We first studied the effect of ischaemia alone, then of lysoPC, TDC, or TCDC alone, and finally of ischaemia together with lysoPC, TDC, or TCDC on the permeability to sodium fluorescein in a ligated loop of the distal ileum in the rat. Longer periods of ischaemia alone (10 min or more) caused increased permeability, as did high concentrations (10 mM) of any of the agents. Low concentrations (1 mM) of lysoPC alone did not alter the gut permeability, but it significantly potentiated the increased permeability caused by 30 min of ischaemia. In contrast, 1 mM TDC or TCDC did not influence the permeability after 30 min of ischaemia. These findings imply that the ischaemic small intestine may be damaged by small amounts of lysoPC, with increased absorption of potentially pathogenic compounds as a possible consequence. They also point to the possibility that endogenously formed lysoPC may play a role in the mucosal damage and the increased permeability that occurs after small-intestinal ischaemia.

Animals↗