Allopurinol
Desensitization to allopurinol in patients with gout and cutaneous reactions.

Fam AG, Lewtas J, Stein J, Paton TW.

Division of Rheumatology, University of Toronto, Ontario, Canada.

PURPOSE: To determine the efficacy and safety of slow oral desensitization in the management of allopurinol-related pruritic cutaneous eruptions. PATIENTS AND METHODS: Nine patients with renal insufficiency and chronic tophaceous gouty arthritis, who had to interrupt their allopurinol therapy because of an allergic-type pruritic maculopapular eruption, were enrolled in an allopurinol oral desensitization protocol using a schedule of gradually increasing doses. RESULTS: Cautious reinstitution of allopurinol was successfully accomplished in all nine patients, but four individuals required dose adjustment because of development of a mild, recurrent, macular rash early during the protocol at allopurinol doses of less than or equal to 5 mg/d. Transient, postdesensitization cutaneous reactions occurred in two patients, one of whom also had an early rash. CONCLUSION: Oral desensitization to the minor rashes induced by allopurinol is a feasible and acceptably safe approach to therapy, particularly for those with renal insufficiency in whom no substitute urate-lowering drug is available.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1388001&dopt=Abstract allopurinol Zyloprim



Allopurinol
Effects of the anti-ICAM-1 monoclonal antibody, allopurinol, and methylene blue on intestinal reperfusion injury.

Ilhan H, Alatas O, Tokar B, cOlak O, Pasaoglu O, Koku N.

Department of Pediatric Surgery, Osmangazi University, School of Medicine, Eskisehir, Turkey.

PURPOSE: The aim of this study was to evaluate the effect of allopurinol, methylene blue, and a monoclonal antibody to the adhesion molecule ICAM-1 in intestinal ischemia and reperfusion injury. METHODS: The rats were divided into 5 groups. CG (n = 8) was untreated controls, SISG (n = 11) received sterile isotonic saline solution, ICAMG (n = 12) received a monoclonal antibody to rat ICAM-1, ALLOG (n = 12) received allopurinol, and MBG (n = 14) received methylene blue. Intestinal ischemia was performed for 60 minutes followed by 60 minutes of reperfusion. The agents were injected 10 minutes before the reperfusion to animals. After 60 minutes of reperfusion, the plasma samples for myeloperoxidase (MPO) activity, tumor necrosis factor alpha (TNF-alpha) and uric acid levels, and the intestinal biopsies of ileum and jejunum for histopathologic examination were taken. RESULTS: The mucosal damage was attenuated, and TNF-alpha level significantly decreased in ALLOG and ICAMG compared with SISG. The MPO activity was the lowest in ICAMG, and uric acid level was significantly decreased in ALLOG compared with the other groups. Methylene blue decreased TNF-alpha response to reperfusion injury but significantly increased the grade of the mucosal damage and the MPO activity. CONCLUSIONS: This study shows that prereperfusion application of allopurinol and monoclonal antibody to the adhesion molecule ICAM-1 may attenuate the damage caused by intestinal ischemia and reperfusion, but the different time-points for application, the effects observed in the different ischemia and reperfusion durations, and the long-term results also should be investigated in the same experimental model before the final conclusion. Methylene blue was not effective to prevent or attenuate the intestinal tissue injury, but because this was the first study examining the effect of methylene blue on intestinal reperfusion injury, further studies with the different doses, ischemic duration, and application times will be needed.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14614706&dopt=Abstract allopurinol Zyloprim



Allopurinol
Stimulation of healing by free radical scavengers of ischemia-induced acute gastric mucosal injury in the rat.

Salim AS.

University Department of Surgery, Royal Infirmary, Glasgow, U.K.

Allopurinol and dimethyl sulfoxide (DMSO; 1 mL of 1, 2, or 5% by gavage daily) were used to examine the influence of scavenging oxygen-derived free radicals on the healing of reserpine- (5 mg/kg, intraperitoneal) and 5-hydroxytryptamine- (50 mg/kg, intraperitoneal) induced acute ischemic injury of the rat gastric mucosa. Allopurinol and DMSO demonstrated a time- but not dose-dependent power to stimulate healing of this injury. The magnitude of injury produced by reserpine or 5-hydroxytryptamine (serotonin) followed by gavage with allopurinol or DMSO was significantly (p < 0.01) less after day 4 than that after day 3 of this gavage, and the magnitude after day 3 was itself significantly (reserpine, p < 0.001; 5-hydroxytryptamine, p < 0.01) less than that after day 2 of the same gavage. The actions of allopurinol and DMSO were not associated with any significant influence on H+ output. These results suggest that oxygen-derived free radicals are detrimental to the integrity of the rat gastric mucosa and that scavenging them stimulates healing of the ischemia-induced injury of the mentioned mucosa.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1447712&dopt=Abstract allopurinol Zyloprim



Allopurinol
Effects of allopurinol pretreatment with pulmonary flush on lung preservation.

Aiba M, Yokoyama Y, Snow TR, Novitzky D, McKeown PP.

Department of Surgery, University of South Florida, Tampa 33612.

This study was designed to test whether use of allopurinol could improve lung preservation after 6 hours of cold storage. Thirty-two rabbits were divided into four groups (n = 8 each group): (1) the control group received no flush or storage, (2) the EC group received Euro-Collins (EC) solution for both flush and storage, (3) the Allo-F group received Euro-Collins solution with allopurinol (1 mmol/L) for both flush and storage, and (4) the Allo-R group received Euro-Collins solution to which allopurinol (1 mmol/L) was added only to the reperfused blood. For groups 2 through 4, the lungs were flushed (40 ml/kg) in situ, excised, and then stored at 4 degrees C. After storage, the lungs were reperfused for 1 hour with an in vitro blood-perfused ventilated model. Lung function was measured during reperfusion with mean pulmonary arterial pressure, end-inspiratory airway pressure, and blood gas data. The lung wet/dry weight ratio was used to measure lung edema. The lungs in the EC group had a significant increase in mean pulmonary arterial pressure, airway pressure, and wet/dry weight ratio when compared with the control group. The mean pulmonary arterial pressure in either of the groups receiving allopurinol was consistently lower than that in the EC group. The airway pressure in the Allo-R group also significantly decreased compared with the EC group.(ABSTRACT TRUNCATED AT 250 WORDS)

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1457426&dopt=Abstract allopurinol Zyloprim



Allopurinol
Purpurogallin is a more powerful protector of kidney cells than Trolox and allopurinol.

Zeng LH, Wu TW.

Department of Clinical Biochemistry, University of Toronto, Ont., Canada.

Phase contrast and electron microscopic experiments demonstrated that oxyradicals generated with xanthine oxidase and hypoxanthine markedly damage rat kidney mesangial and porcine tubular epithelial cells. Purpurogallin, a phenol found in oak nutgalls, prolongs survival of the xanthine oxidase exposed renal cells three- to nine-fold longer than those without purpurogallin present. At levels equimolar to purpurogallin, either Trolox or allopurinol is less effective in delaying cell necrosis. Purpurogallin scavenges not only xanthine oxidase generated oxyradicals, but also non-enzymatically produced peroxyl radicals, more actively than equimolar levels of Trolox or allopurinol. Purpurogallin inhibits xanthine oxidase with severalfold higher potency than allopurinol and its more active metabolite oxypurinol. Therefore, purpurogallin is a stronger antioxidant than Trolox and a more potent inhibitor of xanthine oxidase than allopurinol as well as oxypurinol.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1476704&dopt=Abstract allopurinol Zyloprim



Allopurinol
Effects of allopurinol on reperfusion arrhythmias in isolated ventricles.

Li GR, Ferrier GR.

Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.

Electrophysiological effects of allopurinol on arrhythmias were studied in isolated segments of guinea pig right ventricular free walls paced from endocardium. A high-gain electrocardiogram as well as transmembrane electrical activity from endo- and epicardium were recorded. Tissues were exposed to simulated ischemia for 15 min and then were reperfused with normal Tyrode solution. Sustained or nonsustained ventricular tachycardia, bigeminy, and trigeminy with characteristics of transmural reentry occurred in early reperfusion in 75% of 20 control preparations. Arrhythmias were associated with prolongation of transmural conduction time and abbreviation of endocardial effective refractory period (ERP). Allopurinol strongly reduced the incidence of reperfusion arrhythmias (20-33%) between 10 and 100 microM, whereas either lower or higher concentrations (5 or 500 microM) were less effective (43 and 50%). Antiarrhythmic efficacy correlated with significant attenuation of reperfusion-induced transmural conduction delay (P less than 0.05 or 0.01). Allopurinol did not affect endocardial conduction times nor did it significantly alter endocardial action potential duration or ERP. Our results indicate that allopurinol exerts antiarrhythmic efficacy during reperfusion by selectively attenuating defects related to anisotropic tissue properties.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1510130&dopt=Abstract allopurinol Zyloprim