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Biomedical subjects

D J Bouchier-Hayes

Publications and source records attributed to D J Bouchier-Hayes.

At least 19 recordsLinked to original sources
PubMed2006

Thrombomodulin expression in colorectal carcinoma is protective and correlates with survival.

Thrombomodulin (TM) is an endothelial receptor that exhibits anticoagulant, antifibrinolytic and anti-inflammatory activity by inhibiting thrombin and cellular adhesion. In this study, the expression and significance of TM was examined in primary colorectal cancer and its prognostic implications explored. TM immunostaining was performed on formalin-fixed, paraffin-embedded tissue sections, from primary lesions of 200 patients with colorectal carcinoma. Institutional Ethical approval was granted and clinical data retrieved from patients' records. All normal colonic tissue expressed TM on endothelial cells. TM tumour cell expression was demonstrated in 53 (26.5%) cases and 147 (73.5%) showed no neoplastic cell staining. On univariate and multivariate analysis TM expression on tumour cells correlated significantly with tumour stage, differentiation, Jass score and 5 year survival. TM expression decreases as overall stage and tumour size increase (P=0.03). In all, 91% TM positive tumours were well differentiated and 85% of TM negative tumours were poorly differentiated (P<0.01). Five year survival rates of patients with positive and negative TM expression were 71 and 41%, respectively. Survival rate was poorer in those patients who were TM negative compared with those who were positive (P<0.01). A total of 101 (50.5%) of the cases were node negative. In this group, 5 year survival rates of patients with positive and negative TM expression were 87.5 and 37.8%, respectively, demonstrating a poorer survival rate for those who are node negative and TM negative at the time of surgery (P<0.001). This study demonstrates that loss of TM is a key indicator in tumour biology and prognosis.

Adenocarcinoma↗
PubMed2005

Correction of anaemia through the use of darbepoetin alfa improves chemotherapeutic outcome in a murine model of Lewis lung carcinoma.

Darbepoetin alfa (Aranesp), Amgen) is a novel erythropoiesis-stimulating protein with a serum half-life longer than recombinant human erythropoietin (Epo), used in the treatment of cancer-associated anaemia. Anaemia is known to adversely affect prognosis and response to treatment in cancer patients. Solid tumours contain regions of hypoxia due to poor vascular supply and cellular compaction. Although hypoxic stress usually results in cell death, hypoxia-resistant tumour cells are genetically unstable and often acquire a drug-resistant phenotype. Increasing tumour oxygenation and perfusion during treatment could have the doubly beneficial outcome of reducing the fraction of treatment-resistant cells, while increasing drug delivery to previously hypoxic tissue. In this study, we examined the effect of darbepoetin alfa on chemotherapy sensitivity and delivery in an in vivo model of Lewis lung carcinoma, shown here to express the Epo receptor (EpoR). We identified that weekly darbepoetin alfa treatment, commencing 10 days before chemotherapy, resulted in a significant reduction in tumour volume compared to chemotherapy alone. This was mediated by the prevention of anaemia, a reduction in tumour hypoxia and a concomitant increase in drug delivery. Darbepoetin alfa treatment alone did not modulate the growth of the EpoR-expressing tumour cells. This study identifies an important role for darbepoetin alfa in increasing the therapeutic index of chemotherapy.

Anemia↗
PubMed2005

A peptide corresponding to the neuropilin-1-binding site on VEGF(165) induces apoptosis of neuropilin-1-expressing breast tumour cells.

There is increasing evidence that vascular endothelial growth factor (VEGF) has autocrine as well as paracrine functions in tumour biology. Vascular endothelial growth factor-mediated cell survival signalling occurs via the classical tyrosine kinase receptors Flt-1, KDR/Flk-1 and the more novel neuropilin (NP) receptors, NP-1 and NP-2. A 24-mer peptide, which binds to neuropilin-1, induced apoptosis of murine and human breast carcinoma cells, whereas a peptide directed against KDR had no effect. Both anti-NP1 and anti-KDR peptides induced endothelial cell apoptosis. Confocal microscopy using 5-(6)-carboxyfluorescein-labelled peptides showed that anti-NP1 bound to both tumour and endothelial cells, whereas anti-KDR bound endothelial cells only. This study demonstrates that NP-1 plays an essential role in autocrine antiapoptotic signalling by VEGF in tumour cells and that NP1-blockade induces tumour cell and endothelial cell apoptosis. Specific peptides can therefore be used to target both autocrine (tumour cells) and paracrine (endothelial cells) signalling by VEGF.

Adenocarcinoma↗
PubMed2005

Hydroxymethylglutaryl co-enzyme A reductase inhibition attenuates endotoxin-mediated inflammatory responses.

BACKGROUND: The aim of this study was to investigate whether inhibition of hydroxymethylglutaryl co-enzyme A reductase attenuates leucocyte-endothelial cell interactions and alters expression of endothelial constitutive nitric oxide synthase (ecNOS) and inducible nitric oxide synthase (iNOS) following exposure to endotoxin. METHODS: Male Sprague-Dawley rats were randomized into control, lipopolysaccharide (LPS) and pravastatin + LPS groups (seven per group). Pravastatin sodium was gavaged at 0.4 mg per kg per day for 5 days, after which LPS 15 mg/kg was administered via the jugular vein. Intravital microscopy was used to determine leucocyte-endothelial cell interactions. RESULTS: Following the administration of LPS there was a significant reduction in leucocyte rolling velocity at 10 min (mean(s.e.m.) 69(3) versus 102(6) per cent of baseline value; P = 0.041), an increase in the number of adherent leucocytes at 10 min (4.5(0.5) versus 2.8(0.3) per 100 microm; P = 0.044) and an increase in the number of leucocytes undergoing transendothelial migration at 30 min (4.2(0.4) versus 1.7(0.4) per field; P = 0.008) compared with controls. Pretreatment with pravastatin significantly attenuated LPS-induced leucocyte-endothelial cell interactions (rolling velocity 89(6) per cent at 10 min, P = 0.038; adherent leucocytes 3.0(0.5) per 100 microm at 10 min, P = 0.038; migrating leucocytes 1.9(0.5) per field at 30 min, P = 0.001). This endothelial protection was associated with maintenance of ecNOS and reduced iNOS expression within mesenteric tissues. CONCLUSION: These data show that pravastatin produces anti-inflammatory effects in response to injurious stimuli by attenuation of leucocyte-endothelial cell interactions.

Analysis of Variance↗
PubMed2005

Thrombomodulin: tumour biology and prognostic implications.

BACKGROUND: Thrombomodulin (TM) is an endothelial receptor that exerts anti-coagulant, anti-fibrinolytic, and anti-inflammatory activity by inhibiting thrombin and cellular adhesion. There is growing evidence that TM plays a role in tumour behaviour. METHODS: The electronic literature (1966-2004) was reviewed with a specific focus on tumour biology. RESULTS: TM is expressed on both the endothelium and tumour cells in several cancers. Loss of expression denotes a more malignant profile with poorer prognosis. Loss of TM is mediated by hypoxia, endotoxin, and various cytokines, while up-regulation can be achieved by pharmacological manipulation (e.g. pentoxyfylline and statins). CONCLUSION: Originally described as an endothelial anticoagulant, TM plays a key role in tumour biology and prognostics, and provides a potential therapeutic target in impeding cancer spread.

Animals↗
PubMed2005

Taurine attenuates CD3/interleukin-2-induced T cell apoptosis in an in vitro model of activation-induced cell death (AICD).

Interleukin (IL)-2 immunotherapy is used for the treatment of metastatic melanoma and renal cell carcinoma and mediates its effects through the clonal expansion of lymphocytes. Although IL-2 remains the most effective form of therapy for these cancers, response rates are poor and dose escalation is hampered by side effects, which include vascular leak and lymphopenia. The mechanism underlying T cell loss is currently unidentified but could be the induction of activation-induced cell death (AICD) mediated by FasL. Our previous studies have shown that the amino acid taurine can attenuate apoptosis induced by a number of factors in different cell types. Here, we induced T cell AICD via CD3 and IL-2 stimulation and investigated the effect of taurine on lymphocyte apoptosis. Anti-CD3-activated Jurkat T cells treated with IL-2 significantly increased FasL expression, which was associated with increased apoptosis. Treatment with taurine prior to stimulation down-regulated FasL protein expression and partially inhibited apoptosis. Inhibition of FasL-signalling resulted in an identical reduction in apoptosis. As the kinetics of AICD are completely different in circulating T cells, we repeated these experiments in such cells to confirm our finding. Stimulation of CD4(+) circulating T cells induced apoptosis in sensitized, but not freshly isolated T cells, which was abrogated partially by taurine. In Jurkat cells it was determined that taurine-mediated down-regulation of FasL protein expression was associated with decreased FasL mRNA expression and reduced NFkappaB activation. These results reveal one possible mechanism underlying the lymphopenia observed with IL-2 immunotherapy, involving increased FasL expression leading to apoptosis. Taurine may be of use in reversing the lymphopenia associated with IL-2, thereby augmenting its immunotherapeutic potential.

Analysis of Variance↗
PubMed2004

Antimetastatic activity of a cyclooxygenase-2 inhibitor.

Cyclooxygenase-2 (COX-2) expression is increased in breast cancer and surgery has been shown to increase the growth of metastatic tumours. We investigated the effect of selective COX-2 inhibition on the growth of metastases in either an experimental metastasis model or following excision of a murine primary breast tumour. 50,000 4T1 mammary carcinoma cells were injected into the mammary fat pad of female BALB/c mice. When the mean TD reached 8+/-0.4 mm, tumours were excised and the mice were randomised into two groups (n=12 per group) to receive daily intraperitoneal injections of the selective COX-2 inhibitor, SC-236 or drug vehicle for 14 days. Alternatively, experimental metastases were established by tail-vein injection of 50,000 4T1 cells. Mice received either the selective COX-2 inhibitor, SC-236 or drug vehicle for 14 days (n=12 per group). SC-236 treatment significantly reduced tumour burden, the number and size of spontaneous metastases following primary tumour excision. SC-236 treatment also reduced tumour burden, the number and size of experimental metastases. Immunohistochemical staining demonstrated that COX-2 inhibition reduced microvessel density and increased apoptosis within both spontaneous and experimental metastases. These data clearly demonstrate that the selective COX-2 inhibitor, SC-236, has potent antimetastatic activity against both spontaneous metastases arising following primary tumour excision and experimental metastases.

Adenocarcinoma↗
PubMed2004

Hydroxy-methylglutaryl-coenzyme A reductase inhibition improves endothelial dysfunction in type-1 diabetes.

OBJECTIVE: We hypothesize that treatment with Pravastatin, a HMG CoA reductase inhibitor would improve flow-mediated dilation (FMD), a nitric oxide dependent phenomenon and the earliest detectable marker of endothelial dysfunction, in asymptomatic patients with type-1 diabetes. MATERIALS AND METHODS: FMD of the brachial artery in response to reactive hyperaemia was measured using high-resolution ultrasonography. Young male patients with type-1 diabetes (n=9) were compared with age matched non-diabetic controls (n=8). RESULTS: The FMD response in the control group was a median increase in diameter of 7.9 (range 3.8-12.6)%. In the diabetic group the FMD response was impaired when compared with controls with a median increase only of 4.4 (range 3.7-5.8)% (p<0.01). Following Pravastatin, 40 mg per day for one month in the diabetic group, there was a significant diameter change in response to reactive hyperaemia with a median of 8.4 (range 6.9-12.6)% (p<0.01). CONCLUSIONS: These data confirm the presence of endothelial dysfunction in young patients with type-1 diabetes. We have shown that 1-month of Pravastatin treatment normalizes FMD. This suggests that HMG CoA reductase inhibitors may have a role in the management of diabetes mellitus, even in the presence of normal serum cholesterol levels.

Adolescent↗
PubMed2004

Improvement in efficacy of chemoradiotherapy by addition of an antiangiogenic agent in a murine tumor model.

BACKGROUND: Chemoradiotherapy improves survival for some cancer patients. Methods of enhancing treatment response would further enhance survival rates. The effect of the addition of an antiangiogenic agent to a chemoradiotherapy regime has not previously been examined. MATERIALS AND METHODS: C57B16 mice were inoculated with 1 x 10(6) Lewis lung carcinoma cells into the flank and randomized to 1 of 10 treatment groups when tumor volume approached 1000 mm(3). Animals received combinations of standard doses of intraperitoneal cisplatin, 5-fluorouracil, and the antiangiogenic agent genistein, together with 10 or 20 Gy of external beam radiotherapy. Animals were sacrificed at day 6 when tumor volume, microvessel density, and serum VEGF were determined. RESULTS: Mean (SEM) tumor volume in the chemoradiotherapy group was 762 (212) mm(3) versus 565 (79) mm(3) in the chemoradiotherapy plus genistein group (P = 0.04, unpaired t-test). The addition of genistein produced a significant reduction in tumor microvessel density (P = 0.01) as well as serum VEGF levels (P < 0.05) compared to those animals receiving chemoradiation alone. CONCLUSIONS: This study provides proof of principle that chemoradiation can be enhanced by the addition of an antiangiogenic agent to the regime and suggests that further examination of such regimes is warranted.

Angiogenesis Inhibitors↗
PubMed2004

Young male smokers have altered platelets and endothelium that precedes atherosclerosis.

BACKGROUND: Cigarette smoking results in abnormalities of platelets and endothelium with platelet dysfunction implicated in vascular complications. Healthy endothelium plays a pivotal role in regulating hemostasis via the inhibition of platelet activation and aggregation. Thus, we examined if platelet dysfunction correlated with serum vWF levels-a circulating marker of endothelial dysfunction. MATERIALS AND METHODS: We tested this hypothesis in young male smokers. The parameters of platelet function tested included: CD62/CD63; Glycoprotein (GP) IIb/IIIa; Platelet function analzyer (PFA) studies, platelet aggregometry, flow assessment of platelet microparticles, platelet-leukocyte interactions and receptor numbers. Endothelial dysfunction was assessed with serum von Willebrand Factor (vWF). RESULTS: There was a significant increase in platelet CD62 receptor expression and aggregation with an associated delay in time to aggregation using PFA. Endothelial dysfunction was represented by higher serum levels of von Willebrand Factor. All other platelet parameters tested were within the standardized reference range. CONCLUSIONS: These initial data suggests that anti-platelet therapy may have a role in reduction of platelet activation and aggregation in young smokers and possibly alter vascular endothelial abnormalities.

Adenosine Diphosphate↗
PubMed2003

Taurine and vitamin C modify monocyte and endothelial dysfunction in young smokers.

BACKGROUND: Endothelial dysfunction initiated by monocyte-endothelial interactions has previously been observed in many vasculopathies, including chronic cigarette smoking. Taurine, a semiessential amino acid, and vitamin C, a naturally occurring antioxidant, have previously been shown to have endothelial protective effects when exposed to proinflammatory insults. Therefore, we hypothesized that taurine and vitamin C would restore endothelial function in young smokers by modifying monocyte-endothelial interactions. METHODS AND RESULTS: Endothelial-dependent vasodilatation was assessed in vivo using duplex ultrasonography, and monocyte-endothelial interactions were assessed in vitro using endothelial cell culture (human umbilical vein endothelial cells [HUVECs]) with monocyte-conditioned medium (MCM). Endothelial-dependent vasodilatation was significantly impaired in young smokers compared with nonsmokers. Pretreatment of young smokers for 5 days with 2 g/d vitamin C and, more significantly, with 1.5 g/d taurine attenuated this response. MCM taken from smokers impaired the release of nitric oxide and increased the levels of endothelin-1 release from HUVECs. When HUVECs were cultured with MCM from smokers who had been treated with taurine, the levels of nitric oxide and endothelin-1 returned toward control levels. This was attributed to an upregulation in endothelial nitric oxide synthase expression. CONCLUSIONS: These observations suggest that taurine supplementation has a beneficial impact on macrovascular endothelial function, and an investigation of its effect on altered endothelial function in dyslipidemic states is warranted.

Adult↗
PubMed2003

Effect of neoadjuvant chemoradiotherapy on angiogenesis in oesophageal cancer.

BACKGROUND: Vascular endothelial growth factor (VEGF) levels are raised in the serum of patients with oesophageal carcinoma. The aim of this study was to evaluate the tumour microvasculature and the role of tumour-associated macrophages in VEGF production after neoadjuvant chemoradiotherapy and surgery for oesophageal cancer. METHODS: Sections from 92 consecutively resected oesophageal tumours were stained for VEGF, von Willebrand factor and CD68. Twenty-seven patients received preoperative chemoradiation and 65 underwent surgical excision alone. The cellular source of VEGF was determined by parallel-section staining. Microvessel density and macrophage count were determined for each tumour by means of image analysis software. RESULTS: There were no significant differences between the two groups in age, sex or tumour type. Local downstaging of disease was evident in most specimens of tumours that had received preoperative chemoradiation. All tumours stained positive for VEGF, including those demonstrating a complete pathological response. Staining of parallel sections confirmed macrophages as the principal source of VEGF. Mean microvessel density was 6.4 per high-power field (h.p.f.) in tumours that received preoperative chemoradiation compared with 5.3 per h.p.f. in those treated by surgery alone (P = 0.130). A significant increase in tumour-associated macrophage infiltration was noted in tumours treated with neoadjuvant chemoradiation (22.1 per h.p.f.) compared with those treated by surgery alone (14.3 per h.p.f.) (P = 0.042). CONCLUSION: Preoperative chemoradiation had little effect on the local angiogenic profile of the tumour in patients with oesophageal cancer. Tumour-infiltrating macrophages seem to be the source of persistent VEGF production after chemoradiotherapy and might explain the raised serum levels. Addition of an antiangiogenic agent to this regimen may be worthwhile in patients with oesophageal carcinoma.

Adenocarcinoma↗
PubMed2003

Clinically relevant thermal preconditioning attenuates ischemia-reperfusion injury.

INTRODUCTION: Thermal preconditioning has previously been shown to attenuate ischemia-reperfusion induced injuries, possible due to increased expression of heat shock proteins (HSP). The model of thermal preconditioning used, however, was not clinically relevant as preconditioning was to 41 degrees C, leading to cellular damage. Our aim was thus to establish a novel and clinically applicable method of preconditioning. MATERIALS AND METHODS: Twenty-six male Sprague-Dawley rats were split into three groups (nine control, nine ischemia-reperfusion, and eight preconditioned followed by ischemia-reperfusion). To precondition the animals, they were anesthetized and, using a water bath, their core temperature was raised by 1 degrees C for 15 min once a day for five successive days. I/R injury consisted of 30 min of aortic cross-clamping followed by 120 min of reperfusion; control animals had a laparotomy only. Indicators of lung injury were tissue myeloperoxidase, broncho-alveolar lavage protein concentration, and tissue edema. Tissue heat shock protein expression was detected by Western blot analysis. RESULTS: Lower torso ischemia-reperfusion causes significant lung injury versus control, with raised levels of myeloperoxidase 4.53 iu/g to 7.88 iu/g (P < 0.05), raised B.A.L. protein concentration 419 microg/ml to 684 microg/ml (P < 0.05) and altered wet dry ratio 4.63 to 5.50. Clinically relevant thermal preconditioning attenuates all of these parameters back to control levels: myeloperoxidase 3.87 iu/g (P < 0.05 vs I/R), B.A.L. to 284 microg/ml (P < 0.01 vs I/R) and wet dry ratio to 4.44 (P < 0.05 vs I/R). Western blot demonstrated increased expression of H.S.P. 72 in the preconditioned group versus control and I/R alone. Western blot demonstrated increased expression of HSP72 in the preconditioned group vs control and I/R alone. CONCLUSIONS: We conclude that clinically applicable thermal preconditioning can attenuate ischemia-reperfusion induced lung injury, possibly through increased expression of HSP72.

Animals↗
PubMed2003

Pharmacological induction of HSP27 attenuates intimal hyperplasia in vivo.

OBJECTIVES: intimal hyperplasia (IH) is a major cause of re-stenosis post-vascular intervention. Induction of heat shock proteins (HSPs), by thermal pre-conditioning, reduces IH. Our aim was to investigate the effect of the pharmacological HSP inducer herbimycin A on IH in the rat carotid balloon injury model. MATERIALS AND METHODS: thirty male Sprague-Dawley rats were randomized into three groups. All groups underwent balloon injury to the left carotid artery. Stress proteins were induced 18 h pre-operatively by heat shock or herbimycin A. Two weeks post-operatively, animals were sacrificed and carotid intima/media area ratio (I/M ratio) calculated using computerized planimetry. Neo-intimal proliferation was assessed immunohistochemically with PCNA (proliferating cell nuclear antigen). Western blot and immunohistochemistry for arterial HSP70 and HSP27 were performed. RESULTS: heat stress and herbimycin significantly reduced the I/M ratio (p < 0.05 vs balloon injury alone). Neo-intimal proliferation was significantly reduced in the heat stress and herbimycin groups (p < 0.05 vs balloon injury alone). Heat stress induced arterial HSP70 and HSP27. Herbimycin A increased arterial HSP27. CONCLUSION: herbimycin A significantly attenuates IH after balloon injury. HSP27 may be the HSP involved in mediating this response. Pharmacological inducers of HSPs may have a therapeutic role to play in preventing re-stenosis post-vascular intervention.

Angioplasty, Balloon↗
PubMed2002

Cyclo-oxygenase inhibition reduces tumour growth and metastasis in an orthotopic model of breast cancer.

The effect of selective and non-selective cyclo-oxygenase inhibition on tumour growth and metastasis in an orthotopic model of breast cancer was investigated. 4T1 mammary adenocarcinoma cells were injected into the mammary fat pad of female BALB/c mice. When tumours reached a mean tumour diameter of 8.4+/-0.4 mm, mice were randomised into three groups (n=6 per group) and received daily intraperitoneal injections of the selective cyclo-oxygenase-2 inhibitor, SC-236, the non selective cyclo-oxygenase inhibitor, Indomethacin, or drug vehicle. Tumour diameter was recorded on alternate days. From 8 days after initiation of treatment, tumour diameter in animals treated with either SC-236 or indomethacin was significantly reduced relative to controls. Both primary tumour weight and the number of lung metastases were significantly reduced in the SC-236 and indomethacin treated mice. Microvessel density was reduced and tumor cell apoptosis increased in the primary tumour of mice treated with either the selective or non-selective cyclo-oxygenase inhibitor. In vitro, cyclo-oxygenase inhibition decreased vascular endothelial growth factor production and increased apoptosis of tumour cells. Our results suggest that cyclo-oxygenase inhibitors will be of value in the treatment of both primary and metastatic breast cancer.

Adenocarcinoma↗
PubMed2002

Oral folic acid improves endothelial dysfunction in cigarette smokers.

INTRODUCTION: Endothelial dysfunction is an early manifestation of the atheromatous process and is evident without overt clinical signs or symptoms of the disease. Cigarette smoking has been shown to be associated with endothelial dysfunction in otherwise healthy adults. Although cessation of smoking is the ideal objective, it is not always attainable, and therefore any strategy to prevent early endothelial dysfunction is desirable. Folic acid is currently under review as a rational therapeutic agent in hyperhomocysteinemia. However, folic acid may modify endothelial function independent of its effect on homocysteine. We therefore investigated the effect of folic acid on endothelial function in young otherwise healthy cigarette smokers. METHODS: Volunteer cigarette smokers (n = 10) and control lifelong nonsmokers were enrolled in the study. Baseline folate, vitamin B12, homocysteine, and cholesterol levels were analyzed. Flow-mediated dilatation, an endothelial-dependent phenomenon, was assessed using ultrasonography. This scan was performed at baseline and following 4 weeks of folic acid supplementation (5 mg/day). RESULTS: There were no significant differences in the baseline hematological investigations between the groups. Homocysteine levels were within normal limits in both groups and did not change following folic acid supplementation. Cigarette smokers demonstrated significant endothelial dysfunction compared to controls (P < 0.005). This difference was significantly attenuated by folic acid supplementation (P < 0.005). CONCLUSION: Folic acid significantly improves endothelial function in otherwise healthy cigarette smokers. This provides a potential therapeutic tool in attenuating the atheromatous process in this group.

Administration, Oral↗
PubMed2002

Inosine modulates gut barrier dysfunction and end organ damage in a model of ischemia-reperfusion injury.

INTRODUCTION: Gut barrier failure is an important source of morbidity in critically ill patients, and patients undergoing aortic cross-clamp. Inosine, an endogenous purine nucleoside without known side effects, formed from the breakdown of adenosine by adenosine deaminase, has been shown to modify the effects of hypoxia on various tissues, including the heart and the brain. MATERIALS AND METHODS: This study examined the effect of inosine on ischemia-reperfusion-induced gut barrier dysfunction and on the associated lung injury. Twenty-four male Sprague-Dawley rats were divided into three groups. Eight were subjected to 60 min of superior mesenteric artery occlusion followed by 4 h of reperfusion. Eight had 100 mg/kg inosine prior to ischemia-reperfusion and 8 had sham laparotomy with encircling but not occlusion of the superior mesenteric artery. RESULTS: Rats treated with inosine had significantly less gut barrier dysfunction. Rats subjected to SMAO sustained a substantial lung injury and this was attenuated by inosine treatment. Serum cytokine levels were also significantly lower. CONCLUSIONS: We conclude that inosine has a beneficial effect in modulating both gut barrier dysfunction and distant organ injury in response to gut ischemia-reperfusion.

Animals↗