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The current population-based matched-cohort study did not support the association between allopurinol therapy in gout patients with normal risk for cardiovascular sequels and beneficial future cardiovascular outcomes. Several important risk factors for cardiovascular disease, such as smoking, alcohol consumption, body mass index, blood pressure were not obtainable in the current retrospective cohort study, thus could potentially bias the effect estimate.
During the follow-up of 18.4 months (mean), 28 primary events occurred. Basal use of allopurinol was a significant beneficial factor (hazard ratio = 0.342, p = 0.0434, standard error = 0.53058) after adjusting for confounding factors.
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Allopurinol, an inhibitor of xanthine oxidase, is indicated in the management of patients with elevated serum and urinary uric acid levels. It was also reported to be beneficial in patients with epilepsy when added to traditional antiepileptic drug. Here, we investigated the effect of allopurinol upon the electrical seizure threshold and its effect on the protective efficacy of common antiepileptic drugs, carbamazepine (CBZ) and valproate (VPA) against maximal electroshock (MES)-induced convulsions in mice. We found that allopurinol administered at doses of 5, 15 or 45 mg/kg, did not affect electrical seizure threshold. When administered acutely or for a prolonged period of time (5 times every 24 h), it did not affect anticonvulsant activity of CBZ and VPAin MES. Free plasma concentration of both anticonvulsants was not affected by allopurinol given at a dose of 45 mg/kg for 5 days. Thus, our results did not support suggestions that allopurinol can be beneficial as add-on drug in the management of epilepsy at least in patients treated with CBZ or VPA.
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Compared with placebo, allopurinol significantly improved endothelium-dependent vasodilation, by both forearm venous occlusion plethysmography (93 ± 67% vs. 145 ± 106%, p = 0.006) and flow-mediated dilation (4.2 ± 1.8% vs. 5.4 ± 1.7%, p < 0.001). Vascular oxidative stress was completely abolished by allopurinol. Central augmentation index improved significantly with allopurinol (2.6 ± 7.0%, p < 0.001) but not with placebo.
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Gender distribution was similar between groups. Mean age was 53.5 +/- 18.9 years for study group and 52.8 +/- 19.8 years for controls. Also, the distribution of benign pathology was similar between groups. Hyperamylasemia was more common in the control group (P = 0.003). Mild PEP developed in two patients from the study group (2.3%) and eight (9.4%) from control group (P = 0.04), seven episodes were observed in high-risk patients of the control group (25%) and one in the allopurinol group (3.3%, P = 0.02). Risk factors for PEP were precut sphincterotomy (P = 0.02), pancreatic duct manipulation (P = 0.002) and multiple procedures (P = 0.000). There were no deaths or side effects.
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The many developments that have occurred and continue to occur have also meant that the quality of life experienced by recipients of a successful graft is excellent, with more than 85% of patients returning to normal life and work (even having children). While long-term survival still occurs more frequently in favorable groups such as children with metabolic abnormalities or biliary atresia, results are still extremely good for adults, with 3-year survival figures after transplantation for cirrhosis in the order of 75%. These figures also continue to improve, and with the skill and enthusiasm that workers in this field display they seem destined to continue unabated.
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Porcine livers were perfused with a newly developed machine perfusion (MP) system. The livers were perfused with modified University of Wisconsin solution (UW) - gluconate. All grafts were procured after acute hemorrhagic shock with the ventilator off. For group 1 (n = 6), grafts were procured after WIT of 60 minutes and preserved by hypothermic MP (HMP) for 3 hours. For group 2 (n = 5), grafts were preserved with 2 hours of simple cold storage (SCS) and HMP for 2 hours. For group 3 (n = 6), grafts were preserved with 2 hours of SCS and rewarming up to 25°C by MP for 2 hours (RMP). The preserved liver grafts were transplanted orthotopically.
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Livers from fed and fasted mice were perfused with oxygenated Krebs'-Henseleit buffer (RBKB). After depletion of glycogen, 31P and 13C nuclear magnetic resonance spectra were acquired. Livers were flushed with University of Wisconsin solution and stored at 4 degrees C for 0, 24, or 48 hours. At reperfusion with RBKB, recovery of nucleoside triphosphates (NTP) was followed up. After 45 minutes, [3-13C]alanine was added and substrate consumption and metabolic products assessed.
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The aim of this systematic review was to analyze the available literature and define clinical practice guidelines for the use of the following agents for the prevention and treatment of oral mucositis (OM): allopurinol, midline mucosa-sparing radiation blocks, payayor, pentoxifylline, timing of radiation therapy (RT) (morning versus late afternoon), pilocarpine, bethanechol, chewing gum, propantheline, and tetrachlorodecaoxide.
The present work evaluates the ultrastructural changes during cerulein-induced acute pancreatitis in rat, with and without treatment with allopurinol.
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ADTKD-UMOD is defined by the presence of a heterozygous pathogenic variant in UMOD, the gene encoding uromodulin. The majority of persons with ADTKD-UMOD have the following laboratory test abnormalities: elevated serum creatinine (decreased estimated glomerular filtration rate), bland urinary sediment, elevated serum urate level, and reduced fractional excretion of uric acid. In children with the disorder, serum creatinine levels may be normal but elevated serum urate levels are usually present.
The 74.2% of the patients had a prothrombin time (INR) in the therapeutic range; 16.14% had minor complications; 60.2% of the patients complied with the criteria of multiple medication and 88.2% complied with the criteria of multiple medication in the last 6 months. The drugs used with a higher capacity to interact are: anti-ulcer (26.9%), locomotor system (10.7%), cardiovascular drugs (2.2%), lipid lowering drugs (8.6%), and antidiabetics (17.2%). The number of drugs used in the last 6 months is associated with the presence of haemorrhagic complications (odds ratio [OR], 1.10). Allopurinol and pantoprazole had a significant relationship with the presence of minor haemorrhages (OR, 19.25 and 7.37, respectively). The variables associated with the presence of a haemorrhage were: allopurinol (OR, 25.84), number of controls with an INR outside the therapeutic range in the last 6 months (OR, 1.31) and time on treatment (OR, 1.07).
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A very promising approach in drug discovery involves the integration of available biomedical data through mathematical modelling and data mining. We have developed a method called optimization program for drug discovery (OPDD) that allows new enzyme targets to be identified in enzymopathies through the integration of metabolic models and biomedical data in a mathematical optimization program. The method involves four steps: (i) collection of the necessary information about the metabolic system and disease; (ii) translation of the information into mathematical terms; (iii) computation of the optimization programs prioritizing the solutions that propose the inhibition of a reduced number of enzymes and (iv) application of additional biomedical criteria to select and classify the solutions. Each solution consists of a set of predicted values for metabolites, initial substrates and enzyme activities, which describe a biologically acceptable steady state of the system that shifts the pathologic state towards a healthy state.
We conducted an online case-crossover study of individuals with gout over 1 year. The following information was obtained during gout attacks: the onset dates, symptoms and signs, medications, and exposure to potential risk factors, including daily aspirin use and dosage, during the 2-day hazard period prior to the gout attacks. The same exposure information was also obtained over 2-day control periods.
Adenine phosphoribosyltransferase (APRT) deficiency is characterized by excessive production of 2,8-dihydroxyadenine (DHA), which is excreted in the urine, where it is poorly soluble and leads to kidney stone formation and chronic kidney disease (CKD). Kidney stones, the most common clinical manifestation of APRT deficiency, can occur at any age; in at least 50% of affected individuals symptoms do not occur until adulthood. In a significant number of individuals, intratubular and interstitial precipitation of DHA crystals can result in kidney failure (i.e., DHA crystal nephropathy).
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Protozoa possess a wealth of purine-salvage enzymes, many with unique, or unusual, substrate specificities. As a result, many opportunities for the chemotherapist exist. An exemplification is found in the conversion in schistosomes of allopurinol ribonucleoside to the corresponding ribonucleotide followed by further anabolism to the very toxic 4-aminopyrazolo(3,4-d)pyrimidine 1-ribonucleotide. The same organisms convert another inosine analog, formycin B, to the ribonucleotide, but its inhibitory effects appear to be exercised primarily by inhibition of the organism's adenylosuccinate synthase. A substantial segment of the Phylum Protozoa shows no vestigial traces of ability to synthesize purines de novo although thymidylate synthase appears to be present in many. The absence of other tetrahydrofolate catalyzed reactions suggests that these functions were never acquired.
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The aim of this work was to determine the possibility of using the organ preservation solution UW for the enzymatic collagenase digestion step of the isolation of islets of Langerhans, although this solution is a calcium-free medium (collagenase being a calcium-dependent enzyme), high sodium and low potassium medium, which may be toxic for cells at the temperature needed for islet isolation. The rationale behind this work was that porcine islets are fragile, and that islets are poorly protected against oxidative stress: thus the cytoprotective properties of UW solution might be able to protect the islets during the digestion step, and improve the function of the isolated islets. As a first step, we verified that pancreas digestion with collagenase in a modified (i.e. hydroxyethyl starch deprived) UW solution was feasible: islets were randomly isolated from rat pancreas under either conventional conditions (usual ionic solution, IS), when the pancreas was inflated with UW solution (UW), and again when the pancreas was incubated for an additional hour (UW + 1) after inflation with UW and before the digestion step, thus simulating the time lapse between pancreas collection and islet isolation. In the last two conditions, collagenase was dissolved in UW solution for the digestion step.(ABSTRACT TRUNCATED AT 250 WORDS)
Compared to UW alone, significantly fewer apoptotic cells were present in UW + rATG perfused and stored livers. There were early and sustained significant increases in Bcl-X(L) and decreases in Bcl-X(S) with rATG. There was an initial, but not sustained, significant decrease in Bax with rATG. Moreover, there was a significant one-third decrease in caspase-9 production with rATG at 0, 6, 12, and 18 h.
Twenty male Wistar rats were sensitized with lens proteins for eight weeks. Intravenous (IV) therapy was started after anterior capsule disruption in one eye of each animal. Five rats were randomly assigned to each of the four groups: controls, Allo (50 mg/kg bw), Pred (7.5 mg/kg bw) and Allo/Pred (50 mg/7.5 mg per kg bw). Eyes were enucleated 24 hours later and fixed in paraformaldehyde/glutaraldehyde. Sections at three levels were stained with Giemsa and examined using a 0 to 4+ score for each type of inflammatory cell. Granulocytes were seen as neutrophils and eosinophils. Neutrophils were divided into polymorphs and "others", and graded with lymphocytes.
We demonstrated for the first time that conservation with TLM significantly improves the outcome of kidney transplantation in a rat model and should therefore be further studied in larger animals.
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In a series of 10 patients who had been injected with a permanent filler of hydroxymethylmethacrylate and ethylmethacrylate (40%) in hyaluronic acid gel (60%) and had developed adverse reactions with inflammatory nodules after variable time elapsed, biopsies could be obtained for histologic and electron microscopic examinations.
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Comparison of the effect of the Wisconsin University (WU) conservation solution in the graft's functional evolution and survival, and its cost-benefit relationship versus the Eurocollins (EC) solution with regard to cold ischaemia duration in a series of 142 consecutive adults renal transplantations from corpse donor, removed with beating heart. Of 142 kidneys, 92 (64.7%) were kept in WU and 50 (35.2%) in EC. Of the WU group, 62 (67.3%) kidneys were transplanted after a cold ischaemia of under 24 hours and 30 (32.6%) after cold ischaemia of more than 24 hours. In the EC group, 23 (46%) were kept in cold ischaemia for an interval shorter than or equal to 24 hours and 27 (54%) for more than 24 hours. Incidence of initial graft dysfunction (IGD) was greater in the EC groups (65% and 78%) versus the WU groups (39% and 50%), the difference being statistically significant (p). The graft function, as indicated by the creatinine levels was always better in the WU groups. There was a decreased need for complementary dialysis sessions, less days of oliguria and shorter hospitalization in the WU groups (p). There were no significant differences in the four series with regard to rejection episodes, cyclosporin-related nephrotoxicity, and vascular and urinary tract complications. All of which turn cost-effective the higher cost per litre of the WU versus the EC solution. Graft survival at 12 and 24 months was also significantly (p) higher for grafts kept in WU. This paper presents the results obtained in the analysis of our transplanted patients. In our experience, the WU solution allows better conservation of renal grafts, with less IGD and better graft survival at 12 and 24 months. These results turn cost-effective the higher cost per litre of the WU versus the EC solution.