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Br J Surg. 2002 Dec;89(12):1572-80.
Allopurinol and superoxide dismutase protect against leucocyte-endothelium interactions in a novel model of colonic ischaemia-reperfusion.

Riaz AA, Wan MX, Schafer T, Dawson P, Menger MD, Jeppsson B, Thorlacius H.

Department of Surgery, Malmo University Hospital, Lund University, Malmo, Sweden, Imperial College School of Medicine, Hammersmith Hospital, London, UK.

BACKGROUND: Leucocyte recruitment is a key feature in ischaemia-reperfusion (I/R)-triggered tissue injury. However, the mechanisms underlying leucocyte-endothelium interactions in the large bowel remain elusive because of a previous lack of models to examine the colonic microcirculation. The aim of this study was to develop and validate a novel method for studying reperfusion-induced leucocyte-endothelium interactions in the colon. METHODS: The superior mesenteric artery was occluded for 30 min in male C57/Bl6 mice and leucocyte responses were analysed in colonic venules after 30-240 min of reperfusion. Analysis of leucocyte rolling and adhesion in colonic venules was made possible by an inverted approach using intravital fluorescence microscopy. RESULTS: Thirty minutes of ischaemia and 120 min of reperfusion induced the strongest and most reproducible increase in leucocyte rolling and adhesion. This was associated with a significant increase in colonic levels of malondialdehyde (MDA). Administration of allopurinol and superoxide dismutase reduced I/R-induced leucocyte responses in a dose-dependent manner. Pretreatment with allopurinol attenuated the tissue content MDA in the colon by more than 60 per cent. CONCLUSION: A new method for examining I/R-induced leucocyte responses in the colonic microcirculation is described. Oxygen free radicals play an important role in triggering leucocyte rolling and adhesion in colonic venules.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12445069&dopt=Abstract

med.muni.cz

BACKGROUND: Acute renal failure (ARF) during the course of cytostatic therapy is a serious complication. ARF can be isolated or became as component of tumour lysis syndrome (TLS). TLS comprises a number of metabolic abnormalities (hyperuricemia, hyperphosphatemia, hyperkalemia, azotemia and hypocalcemia) which are associated with lymphoproliferative malignancies following spontaneous or chemotherapy-induced cytolysis. There exist probably no clear prediction for the development of TLS that could enable early detection of manifestation of this severe condition. SUBJECTIVE: Conventional management with aggressive hydration, alkalization of the urine, administration of allopurinol, and the slow introduction of chemotherapy is often unable to prevent metabolic instability and ARF. Recent studies define a subgroup of patients at higher risk of renal failure during induction chemotherapy. ARF was encountered during initial therapy of patients with a lactate dehydrogenase (LDH) index greater than 3.3. METHODS AND MATERIAL: A retrospective analysis of 10 children (3 girls, 7 boys, average age 9.7 years) with LDII index greater than 3.3 has been done. All children were treated for lymphoproliferative malignancy with conventional preventive measures. RESULTS: Three children needed haemodialysis--2 boys had fully expressed TLS with ARF shortly after starting chemotherapy, in 1 boy the dialysis was indicated because of extreme hyperuricemia and high creatinine level presented before chemotherapy. We consider that LDH index is not specific criterium for prediction of TLS. In conclusion, our cases demonstrate the pathophysiologic spectrum of ARF in TLS between hyperuricemia and hyperphosphatemia. CONCLUSION: The LDH index, urine output, and hyperphosphatemia could be used to identify those paediatric patients who would benefit from the prospective use some of extracorporeal elimination methods. Further investigation of this techniques in a larger number of patients is warranted. (Tab. 5, Ref. 12.)

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12448566&dopt=Abstract

mailer.uni-marburg.de

PURPOSE: To investigate the effect of topical allopurinol on experimental corneal burns and to compare this to established treatment modalities such as topical prednisolone and acetylcysteine. METHODS: Twenty Wistar rats were randomly assigned to four groups (n=5 each). The groups were controls (normal saline), allopurinol 0.4% eye drops, prednisolone acetate 1% eye drops and acetylcysteine 8% eyedrops. Corneal burn was induced using a 3 mm paper disc soaked in 1N NaOH for 60 seconds. Drops were instilled 6 times per day. In addition, one drop/day ofloxacine was given to prevent secondary infections. Eyes were enucleated 50 hours later and fixed in 4.5% formaldehyde. Three histological levels of each globe were stained with hematoxylin-eosin and examined by two independent masked investigators using a 0 to 4+ inflammatory score. All pair-wise multiple comparison procedures (Student-Newman-Keuls method) were applied for statistical work-up. RESULTS: All three substances significantly reduced the number of histologically visible inflammatory cells compared to the control group (p<0.05). CONCLUSIONS: In the present study, topical allopurinol was as effective as established drugs, namely steroids and acetylcysteine, in the early treatment of experimental alkali corneal burns.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12474917&dopt=Abstract












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