allopurinol and Edema

Intestinal transplantation has become the therapy of choice for patients with intestinal failure and life-threatening complications from total parenteral nutrition. Results, however, remain inferior as compared with other transplant types with the quality of the organ graft as the most important factor of outcome after transplantation. The intestine is extremely sensitive to ischemia. Unfortunately, a relatively long ischemic preservation period is inevitable. The current standard in organ preservation [cold storage (CS) with University of Wisconsin solution] was developed for kidney/liver preservation and is suboptimal for the intestinal graft despite good results for other organs. This review aimed at appraising the results from the use of previously applied and recently developed preservation solutions and techniques to identify key areas for improvement. As the studies available do not reveal the most effective method for intestinal preservation, an optimal strategy will result from a synergistic effect of different vital elements identified from a review of published material from the literature. A key factor is the composition of the solution using a low-viscosity solution to facilitate washout of blood, including amino acids to improve viability, impermeants and colloids to prevent edema, and buffer for pH-homeostasis. Optimizing conditions include a vascular flush before CS and luminal preservation. The most effective composition of the luminal solution and a practical, clinically applicable optimal technique are yet to reach finality. Short-duration oxygenated arterial and/or luminal perfusion have to be considered. Thus, a tailor-made approach to luminal preservation solution and technique need further investigation in transplant models and the human setting to develop the ultimate technique meeting the physiologic demands of the intestinal graft during preservation.

Topics: Adenosine; Allopurinol; Amino Acids; Animals; Antioxidants; Buffers; Colloids; Disaccharides; Edema; Electrolytes; Glutamates; Glutathione; Histidine; Humans; Insulin; Intestine, Small; Mannitol; Organ Preservation; Organ Preservation Solutions; Raffinose; Viscosity

Oxygen-derived free radicals have been implicated as contributors to the development of lower limb oedema observed after femoropopliteal bypass grafting. This study investigates the occurrence of free radical-induced lipid peroxidation after this operation and the possible effects of allopurinol (xanthine oxidase inhibitor) in reducing free radical injury in order to minimise lower leg oedema. Twenty-nine patients undergoing femoropopliteal bypass surgery were randomised in a double blind fashion into two groups; those in one were given allopurinol 200 mg orally (n = 15) at 24 h and 2 h preoperatively and again at 24 h postoperatively, while those in the second group received a placebo (n = 14). Daily lower limb volume was calculated to assess swelling. Blood samples were taken from the femoral vein for measurements of malondialdehyde (MDA), an end product of lipid peroxidation, before the application of the femoral artery clamp, just prior to and immediately after clamp release, and at 20 minute intervals thereafter for 1 hour. The increase in lower limb volume in the placebo group was almost twice (8.9 +/- 1.6%) that of the allopurinol group (4.6 +/- 1%; p = 0.02). Six out of the 14 patients receiving placebo suffered swelling of 10% or more of original lower limb volume in comparison to only one out of 15 in those given allopurinol (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Allopurinol; Blood Vessel Prosthesis; Double-Blind Method; Edema; Femoral Artery; Free Radical Scavengers; Humans; Intermittent Claudication; Leg; Lipid Peroxidation; Malondialdehyde; Popliteal Artery; Postoperative Complications

Acute inflammation and hyperuricemia are associated with gouty arthritis. As an edible and therapeutic mushroom,

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Arthritis, Gouty; Edema; Hyperuricemia; Interleukin-8; Ligands; Matrix Metalloproteinase 9; Mice; Rats; Rodentia; Tumor Necrosis Factor-alpha; Uric Acid; Xanthine Oxidase

Gold nanoparticles (AuNPs) are gaining a lot of attention in recent decades from researchers due to their unique optoelectronic properties and their significance in the field of biomedicine. Keeping this in view, our research work was designed to investigate gold nanoparticles obtained by using a fungal endophytic strain Chaetomium globosum, isolated from Vitex negundo which showed significant activity on enzyme inhibition. In the present study, the fungal isolate C. globosum was characterized using HPLC and LC-MS. A novel compound Catechin was matched with standard Catechin. Further, the endophyte C. globosum extract was utilized to synthesize gold nanoparticles (CgAuNPs) which was analysed by UV-visible spectroscopy. The CgAuNPs exhibited wine red color and the absorption peak appeared at 542 nm confirming the formation of the AuNPs. Further, Fourier Transmission Infrared Spectroscopy (FTIR) was performed to confirm the various functional groups present in mycosynthesized CgAuNPs. FTIR analysis demonstrated the presence of amines, flavonoids, as well as the presence of amide I linkage which possibly reduces Au

Topics: Acetic Acid; Animals; Anti-Inflammatory Agents; Behavior, Animal; Carrageenan; Catechin; Chaetomium; Cyclooxygenase 2; Disease Models, Animal; Edema; Endophytes; Female; Gold; HeLa Cells; Humans; Hydrogen-Ion Concentration; Inflammation; Lipoxygenase; Male; Metal Nanoparticles; Mice; Plant Leaves; Vitex; Xanthine Oxidase

Topics: Animals; Anti-Inflammatory Agents; Edema; Gout; Gout Suppressants; Humans; Hyperuricemia; Mice; Mice, Nude; Oryza; Peptides; Plant Extracts; Uric Acid; Xanthine Oxidase

The present study aimed to test the anti-inflammatory and xanthine oxidase inhibitory activities of two synthesized molecules and compare them to routinely prescribed nonsteroidal anti-inflammatory drugs (NSAIDs), such as diclofenac and the serum urate-lowering drug, allopurinol. The anti-inflammatory effects of the designed compounds (A and B) were evaluated in carrageenan (CAR)-induced paw edema in mice. The levels of nitric oxide and myeloperoxidase activity were measured in paw skin using biochemical methods. Additionally, prostaglandin E2 (PGE2), C-reactive protein (CRP), cyclooxygenase-2 (Cox-2), tumor necrosis factor-α (TNFα), interleukin (IL)-1β, IL-2 and IL-10, and monocyte chemoattractant protein-1 (MCP1) were assessed by enzyme-linked immunosorbent assay (ELISA). The expression of inflammation-related genes was confirmed by real-time qPCR. The expression of inducible nitric oxide synthase (iNOS) and nuclear factor-kappa B (NF-κB) were estimated using immunohistochemistry, and xanthine oxidase inhibitory activity was evaluated using an in vitro assay. The results revealed that compounds A and B decreased inflammation, as was observed by a reduction in the elevation of all the tested markers. In addition, the tested compounds markedly decreased paw swelling, mobilization of inflammatory cells, iNOS-, and NF-κB-immunoreactive cells in a mouse model of paw edema. Interestingly, both compounds were potent xanthine oxidase inhibitors as well as Cox inhibitors with higher activity in favor of compound B providing potential dual acting series of anti-hyperuricemic and anti-inflammatory therapeutic agents.

Topics: Animals; Anti-Inflammatory Agents; C-Reactive Protein; Cells, Cultured; Chemokine CCL2; Cyclooxygenase 2; Dinoprostone; Edema; Gout Suppressants; Interleukins; Male; Mice; NF-kappa B; Nitric Oxide; Nitric Oxide Synthase Type II; Peroxidase; Skin; Tumor Necrosis Factor-alpha; Xanthine Oxidase

Topics: Anacardiaceae; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Gouty; Chalcone; Dose-Response Relationship, Drug; Edema; Enzyme Inhibitors; Flavanones; Hyperuricemia; Inflammation; Male; Mice; Mice, Inbred Strains; Molecular Structure; Oxonic Acid; Structure-Activity Relationship; Uric Acid; Xanthine Oxidase

Gout is a disorder that triggers a severe inflammatory reaction which generates episodes of intense pain and discomfort to the patient. Arctium minus (Hill) Bernh. (Asteraceae) is known as "burdock" and displays anti-inflammatory, antinociceptive, against rheumatic pain and radical-scavenging activities. Species of the genus Arctium have been used in assistant therapy of gout and other inflammatory processes. We investigated the antinociceptive and anti-edematogenic effects of the crude extract of A. minus seeds in an acute gout attack model induced by intra-articular injection of monosodium urate (MSU) crystals in adult male Swiss mice (25-30 g). The crude extract of A. minus (100 mg/kg, p.o.) reduced the mechanical allodynia induced by the injection of MSU (1.25 mg/site, i.a.) from 4 until 8 h after its administration. A. minus seeds crude extract prevented mechanical allodynia at doses of 30 and 100 mg/kg, but not 10 mg/kg. Allopurinol (10 µg/mL) and A. minus crude extract (10-300 µg/mL) inhibited the xanthine oxidase activity in vitro. The A. minus seeds crude extract did not cause adverse effects since did not change the toxicological parameters evaluated. A. minus crude extract can be used as an assistant therapy of gout pain, supporting its traditional use, without causing adverse effects.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Arctium; Disease Models, Animal; Edema; Gout; Hyperalgesia; Inflammation; Male; Mice; Plant Extracts; Xanthine Oxidase

Gnaphalium affine D. Don is a folk medicine of China believed to be efficacious in the treatment of many ailments, including hyperuricemia and gout.. Based on a previous study, we isolated two flavones, luteolin and luteolin-4'-O-glucoside, from G. affine. Our aim was to assess the potential beneficial effects of treatment and mechanisms of these two flavones on hyperuricemia and acute gouty arthritis.. The model of potassium oxonate (PO)-induced hyperuricemia and monosodium urate (MSU) crystal-induced inflammation in mice has been established. We evaluated serum uric acid (Sur), xanthine oxidase (XO) activity, protein expression of urate transporter 1 (mURAT1) and glucose transporter 9 (mGLUT9) in renal and kidney protection in a hyperuricemia model. In addition, paw swelling and levels of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in serum were assessed in MSU crystal-induced mice.. Luteolin and luteolin-4'-O-glucoside showed a potent clinical effect in treating hyperuricemia and gout. We observed that the two flavones possess potent effect in hyperuricemia mice by decreasing the level of mURAT1 and inhibiting XO activity, which contribute to enhancing uric acid (UA) excretion and improving hyperuricemia-induced renal dysfunction. In addition, luteolin and luteolin-4'-O-glucoside also alleviated paw swelling and inflammation induced by MSU crystals. Further investigation implied that luteolin and luteolin-4'-O-glucoside improved the symptoms of inflammation by decreasing the levels of IL-1β and TNF-α.. The present study suggests that luteolin and luteolin-4'-O-glucoside could be developed as therapeutics for treating hyperuricemia and gouty arthritis.

Topics: Animals; Arthritis, Gouty; Disease Models, Animal; Drugs, Chinese Herbal; Edema; Glucose Transport Proteins, Facilitative; Glucosides; Gnaphalium; Hyperuricemia; Interleukin-1beta; Kidney; Luteolin; Male; Mice, Inbred ICR; Organic Anion Transporters; Uric Acid; Xanthine Oxidase

The Gnaphalium affine D. Don is used in China as a folk medicine to treat gout, anti-inflammatory, antitussive and expectorant activities. The aim of this study was to evaluate the potential of the extract of G. affine to treat hyperuricemia and acute gouty arthritis in animal model.. G. affine extract was evaluated in an experimental model with potassium oxonate (PO) induced hyperuricemia in mice which was used to evaluate anti-hyperuricemia activity and xanthine oxidase (XO) inhibition. Therapies for acute gouty arthritis was also investigated on monosodium urate (MSU) crystal induced paw edema model.. G. affine extract showed expressive results on active in reducing serum uric acid (Sur) through effect renal mGLUT9 and mURAT1 mainly and inhibit XO activity in vivo. The extract of G. affine also showed significant anti-inflammatory activity and reduced the paw swelling on MSU crystal-induced paw edema model. Meanwhile, eight major compounds were identified by HPLC-ESI-QTOF-MS/MS.. The extract of G. affine showed significant effect on evaluated models and therefore may be active agents for the treatment of hyperuricemia and acute gouty arthritis.

Topics: Animals; Anti-Inflammatory Agents; Arthritis, Gouty; Chromatography, High Pressure Liquid; Disease Models, Animal; Edema; Gnaphalium; Hyperuricemia; Male; Mice; Mice, Inbred ICR; Oxonic Acid; Plant Extracts; Tandem Mass Spectrometry; Uric Acid; Xanthine Oxidase

Lychnophora passerina (Mart ex DC) Gardn (Asteraceae), popularly known as Brazilian arnica, is used in Brazilian folk medicine to treat pain, rheumatism, bruises, inflammatory diseases and insect bites.. Investigate the influence of the seasons on the anti-inflammatory and anti-hyperuricemic activities of ethanolic extract of L. passerina and the ratio of the goyazensolide content, main chemical constituent of the ethanolic extract, with these activities.. Ethanolic extracts of aerial parts of L. passerina were obtained from seasons: summer (ES), autumn (EA), winter (EW) and spring (EP). The sesquiterpene lactone goyazensolide, major metabolite, was quantified in ES, EA, EW and EP by a developed and validated HPLC-DAD method. The in vivo anti-hyperuricemic and anti-inflammatory effects of the ethanolic extracts from L. passerina and goyazensolide were assayed on experimental model of oxonate-induced hyperuricemia in mice, liver xanthine oxidase (XOD) inhibition and on carrageenan-induced paw edema in mice.. HPLC method using aqueous solution of acetic acid 0.01% (v/v) and acetonitrile with acetic acid 0.01% (v/v) as a mobile phase in a gradient system, with coumarin as an internal standard and DAD detection at 270nm was developed. The validation parameters showed linearity in a range within 10.0-150.0µg/ml, with intraday and interday precisions a range of 0.61-3.82. The accuracy values of intraday and interday analysis within 87.58-100.95%. EA showed the highest goyazensolide content. From the third to the sixth hour after injection of carrageenan, treatments with all extracts at the dose of 125mg/kg were able to reduce edema. Goyazensolide (10mg/kg) showed significant reduction of paw swelling from the second hour assay. This sesquiterpene lactone was more active than extracts and presented similar effect to indomethacin. Treatments with ES, EA and EP (125mg/kg) and goyazensolide (10mg/kg) reduced serum urate levels compared to hyperuricemic control group and were able to inhibit liver XOD activity. One of the mechanisms by which ES, EA, EP and goyazensolide exercise their anti-hyperuricemic effect is by the inhibition of liver XOD activity. Goyazensolide was identified as the main compound present in ES, EA, EW and EP and it is shown to be one of the chemical constituents responsible for the anti-inflammatory and anti-hyperuricemic effects of the ethanolic extracts.. The anti-inflammatory and anti-hyperuricemic activities of the ethanolic extracts from L. passerina were not proportionally influenced by the variation of goyazensolide content throughout the seasons. The involvement of goyazensolide on in vivo anti-inflammatory and anti-hyperuricemic activities of L.passerina extracts was confirmed, as well as the possibility of participation of other constituents on these effects. This study demonstrated that the aerial parts of L. passerina may be collected in any season for use as anti-inflammatory agent. For use in hyperuricemia, the best seasons for the collection are summer, autumn and spring. The ethanolic extract of L. passerina and goyazensolide can be considered promising agents in the therapeutic of inflammation, hyperuricemia and gout.

Topics: Animals; Anti-Inflammatory Agents; Asteraceae; Brazil; Bridged-Ring Compounds; Chromatography, High Pressure Liquid; Disease Models, Animal; Edema; Ethanol; Furans; Gout; Gout Suppressants; Hyperuricemia; Indomethacin; Inflammation; Male; Medicine, Traditional; Mice; Plant Components, Aerial; Plant Extracts; Seasons; Sesterterpenes; Xanthine Oxidase

Granulomatous reactions to tattoo ink are most commonly associated with mercury sulfide, a component of red pigments. Treatment options show limited results. Allopurinol, an inhibitor of xanthine oxidase, has been reported as a successful alternative treatment to granulomatous disorders, such as sarcoidosis and granulomatous reactions to fillers and tattoos. We report a case of granulomatous reaction to red tattoo pigment treated with allopurinol for 6 months. Good clinical improvement could be noticed during this time. Two months after we stopped the treatment, the lesion recurred. Allopurinol emerges as an important drug for the management of granulomatous reactions caused by tattoo pigments. Based on the significant clinical improvement noticed during its use, we recommend new studies to elucidate all the potential benefits of the use of allopurinol for the treatment of granulomatous reactions to tattoo ink.

Topics: Allopurinol; Coloring Agents; Edema; Enzyme Inhibitors; Female; Granuloma; Humans; Recurrence; Tattooing; Xanthine Oxidase; Young Adult

Jatropha isabellei Müll Arg. (Euphorbiaceae) is a medicinal plant that has been used in South American folk medicine for the treatment of arthritic diseases, particularly gout.. This study was designed to verify the antinociceptive, anti-inflammatory and hypouricemic potential of Jatropha isabellei.. Rats were orally administered with the crude extract (100-300 mg/kg) or a fraction that is rich in alkaloids (0.15 mg/kg) of Jatropha isabellei. An intra-articular (i.a.) injection of 50 μl of monosodium urate (MSU) crystals (1.25mg/site) was used to generate the gout model to assess the effect of the treatment on nociception (thermal and mechanical hyperalgesia) and inflammation (oedema and neutrophil infiltration). The effect of Jatropha isabellei on the serum levels of uric acid was evaluated in a model of hyperuricaemia induced by the intraperitoneal injection of potassium oxonate (250 mg/kg). The side effects were analysed using an open-field test, gastric lesion assessment and by measuring the levels of the ALT and AST enzymes.. Our study demonstrated that the crude extract of Jatropha isabellei and a fraction rich in alkaloids were able to prevent the thermal hyperalgesia, mechanical allodynia, oedema and neutrophil infiltration induced by intra-articular MSU injection in rats. On the other hand, treatment with Jatropha isabellei did not alter the uric acid levels increased by potassium oxonate in the hyperuricaemia model. In addition, Jatropha isabellei did not induce gastric lesions or liver damage and did not alter spontaneous locomotor activity.. The crude extract of Jatropha isabellei and its fraction rich in alkaloid presents antinociceptive and anti-inflammatory effects in a rat gout model, similar to that observed after treatment with colchicine, supporting the traditional use of this plant in gouty patients.

Topics: Alkaloids; Animals; Anti-Inflammatory Agents; Arthritis, Gouty; Biomarkers, Pharmacological; Disease Models, Animal; Edema; Hyperalgesia; Hyperuricemia; Jatropha; Male; Motor Activity; Neutrophil Infiltration; Oxonic Acid; Peroxidase; Phytotherapy; Plant Extracts; Rats; Stomach Ulcer; Uric Acid; Xanthine Oxidase

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare, severe adverse drug reaction. The aim of this study was to characterize the aetiology, clinical features, laboratory findings, and management of patients with DRESS, diagnosed from January 2005 to April 2010 in a tertiary centre in Thailand. Twenty-seven patients were included in the study with a mean age of 52 years. Phenytoin, allopurinol, and nevirapine were the most commonly implicated medications. Mean duration of drug administration before the onset of symptoms was 34 days. The latent period was longer for allopurinol (103 days) and shorter for nevirapine (10 days). Skin rash was seen in all patients, while fever and lymphadenopathy were found in 88.9% and 22.2%, respectively. Hepatic and haematological involvement were the two most common systemic complications, occurring in 96.3% and 85.2%, respectively. Most patients were treated with systemic corticosteroids, for a mean duration of 49 days. The mortality rate in this study was 3.7%. Early detection and discontinuation of the suspected drug are the key steps of management.

Topics: Adult; Aged; Aged, 80 and over; Allopurinol; Anti-HIV Agents; Anti-Inflammatory Agents; Anticonvulsants; Dexamethasone; Drug Eruptions; Edema; Enzyme Inhibitors; Eosinophilia; Face; Female; Fever; Humans; Liver; Male; Middle Aged; Nevirapine; Phenytoin; Prednisolone; Pruritus; Recurrence; Retrospective Studies; Thailand; Time Factors; Withholding Treatment; Young Adult

A series of synthesized novel biscoumarin-chalcone hybrids were evaluated for their anti-inflammatory and antioxidant activity. The tested compounds significantly inhibit the carrageenin induced paw oedema in albino rats and also exhibit important scavenging activities. These compounds thus constitute an interesting template for the design of new therapeutic tools against inflammation.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Chalcone; Coumarins; Edema; Microsomes; Rats

Tynanthus panurensis (Bureau) Sanwith (Bignoniaceae) is a liana vine used in traditional Amazonian medicine as a tonic and energizer as well as a treatment for rheumatism. These traditional indications prompted this study of the antioxidant and anti-inflammatory activities of T. panurensis bark extract (ETP). Phytochemical analysis of ETP showed the presence of saponins and a high concentration of phenols and flavonoids. A battery of in vitro tests revealed that the extract has free radical-scavenging antioxidant properties and reduces microsomal lipid peroxidation, uric acid synthesis, and tumor necrosis factor-α production. The anti-inflammatory properties of ETP were further confirmed in vivo in a rat carrageenan edema model, in which the extract exhibited a potent activity. These results support the idea that T. panurensis bark extract could be beneficial for treating inflammation and are in agreement with one of the main traditional uses of this plant.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Bignoniaceae; Edema; Enzyme Inhibitors; HL-60 Cells; Humans; Lipid Peroxidation; Liver; Medicine, Traditional; Plant Bark; Plant Extracts; Random Allocation; Rats; Rats, Sprague-Dawley; Rats, Wistar; South America; Tumor Necrosis Factor-alpha; Xanthine Oxidase

Aristotelia chilensis leaves (Elaeocarpaceae) are used in Chilean folk medicine to treat pain and inflammation. A bioguided study was carried out on serial extracts (hexane, dichloromethane, methanol, aqueous extract (INFU) and a crude mixture of alkaloids (ALK-MIX). All extracts were evaluated for (1) topical administration against both arachidonic acid and 12-deoxyphorbol-13-decanoate (TPA)-induced inflammation in mice and (2) per-os administration against inflammation by λ-carrageenan-induced paw oedema in guinea-pigs and (3) topical analgesia in tail flick and formalin models and per-os writhing test in mice.. Greater anti-inflammatory effects were obtained against TPA with dichloromethane extract and methanol extract (63.9 and 66.0%, respectively). INFU showed the most potent effect (56.2%) against arachidonic acid. Greater effects were obtained in the writhing test with hexane and dichloromethane extracts (89.2% both). In the topical analgesia models, all the extracts and ALK-MIX were active with exception of the hexane extract in the formalin assay. In tail flick test, ALK-MIX and the methanol extract were the most active (58.2 and 55.2%, respectively). In relation to the tail formalin assay, the methanol extract (74.1%) was the most active. Concerning antioxidant activity, both INFU and the methanol extract were the most active either in the inhibition of xanthine oxidase (52.9 and 62.7%, respectively) or in the DPPH free radical scavenging activity (EC50 (concentration that produced 50% of activity) = 12.1 and 9.7 µg/ml, respectively).. Aristoteline, aristone, serratoline and hobartinol were isolated from ALK-MIX. Ursolic acid, friedelin and quercetin 5,3'-dimethyl ether were present in the dichloromethane extract while quercetin 3-O-β-D-glucoside and kaempferol were present in the methanol extract. From INFU were isolated protopine, aristoteline and caffeic and ferulic acids.. The effects of A. chilensis are herein demonstrated, validating its use in traditional medicine. Protopine is reported for the first time in Elaeocarpaceae.

Topics: Administration, Topical; Alkaloids; Analgesia; Analgesics; Animals; Anti-Inflammatory Agents; Antioxidants; Arachidonic Acid; Behavior, Animal; Biphenyl Compounds; Carrageenan; Chile; Edema; Elaeocarpaceae; Female; Formaldehyde; Guinea Pigs; Inflammation; Male; Medicine, Traditional; Mice; Mice, Inbred Strains; Pain; Phorbol Esters; Phytotherapy; Picrates; Plant Extracts; Plant Leaves; Xanthine Oxidase

The synthesis and characterization of 3-formylchromone (1) and its derivatives 2-24 and evaluation of their potential antiinflammatory activities is reported here. These compounds were characterized by (1)H NMR, EI MS, IR, and UV spectroscopic techniques and elemental analysis. The synthesized compounds were evaluated by using various in vitro and in vivo assay models for antiinflammatory activity and their effects were compared with known standard drug such as aspirin and indomethacin. Among all tested compounds, 1, 2, 5, 6, 9, 14, 16-19, 21-23, showed promising antiinflammatory activities. The results and SAR has been discussed in this report.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Carrageenan; Chromones; Cyclooxygenase Inhibitors; Edema; Female; Inflammation; Male; Prostaglandin-Endoperoxide Synthases; Rats; Rats, Wistar; Respiratory Burst; Xanthine; Xanthine Oxidase

Topics: Acute Disease; Adult; Allopurinol; Ankle Joint; Anti-Inflammatory Agents, Non-Steroidal; Arthralgia; Arthritis, Gouty; Celecoxib; Cyclooxygenase 2 Inhibitors; Diagnosis, Differential; Edema; Gout Suppressants; Humans; Male; Pyrazoles; Sulfonamides

The impact of different preservation solutions for washout of kidney grafts was evaluated regarding temperature, kidney weight, remaining red blood cells (RBCs) and histological evaluation after ex vivo washout using 500 mL cold preservation solution at 4 degrees C followed by 24 hours cold storage (CS).. Kidneys retrieved from Landrace pigs (20-30 kg) were immediately washed (warm ischemic time 0 min [WIT 0]), using 500 mL cold University of Wisconsin solution (UW), histidine-tryptophan-ketoglutarate (HTK), or Polysol (PS) followed by 24 hours, CS. Also, kidneys were retrieved after a WIT of 30 minutes followed by washout using HTK or PS.. After washout, the weight of kidneys washed out with HTK had increased, whereas that of organs in the UW or PS group had decreased. After washout with UW, the core temperature of WIT 0 kidneys was lower than that with HTK. The time needed for washout using 500 mL solution was shorter using PS compared with HTK for both WIT 0 and WIT 30 groups. The amount of remaining RBCs was similar between all WIT 0 groups; whereas in the WIT 30 groups the amount was higher in kidneys washed out using HTK compared with PS. Histological evaluation showed less tissue injury among PS-washed kidneys compared with UW or HTK.. Overall, kidneys washed-out with PS showed better preservation of structural integrity after 24 hours, CS compared with either UW or HTK. Washout of warm ischemically damaged kidneys was more effective using PS compared with HTK.

Topics: Adenosine; Allopurinol; Animals; Edema; Erythrocyte Count; Glucose; Glutathione; Insulin; Kidney; Kidney Glomerulus; Kidney Transplantation; Kidney Tubules; Mannitol; Organ Preservation; Organ Preservation Solutions; Potassium Chloride; Procaine; Raffinose; Swine; Tissue Donors

Activated protein C (APC) is a serine protease with anticoagulant and ant-inflammatory activities. APC has been shown to attenuate deleterious effects of ischemia/reperfusion (I/R) injury in many organs. In this study, we aimed to investigate the effects of APC on intestinal mucosal injury induced by superior mesenteric occlusion.. Male Wistar-albino rats were allocated into four groups: (1) sham-operated group, laparotomy without I/R injury (n = 12); (2) sham + APC group, identical to Group 1 except for APC treatment (n = 12); (3) I/R group, 60 min of ischemia followed by 3-h of reperfusion (n = 12); and (4) I/R + APC-treated group, 100 mug/kg injection of APC intravenously, 15 min before reperfusion (n = 12). We evaluated the degree of intestinal mucosal injury on a grading scale from 0 to 5, histopathologically, and by measuring activities of oxidative and antioxidative enzymes as well as nitrate/nitrite levels, biochemically. Intestinal edema was estimated by using wet/dry weight ratios. The plasma levels of proinflammatory cytokines and D-dimer were measured. Animal survival was observed up to 1 wk.. Intestinal mucosal injury scores were significantly decreased with APC administration (P < 0.05). APC treatment significantly reduced activities of oxidative enzymes and nitrate/nitrite levels in the intestinal tissues, and plasma levels of proinflammatory cytokines and D-dimer, and also significantly increased activities of antioxidative enzymes in the intestinal tissues (P < 0.05). Intestinal edema was significantly alleviated with APC treatment (P < 0.05). The survival rate of rats in the APC-treated group were significantly higher than that of the I/R-treated group (P < 0.05).. This study clearly showed that APC treatment significantly attenuated intestinal mucosal injury caused by superior mesenteric ischemia/reperfusion. Further clinical studies are required to clarify whether APC has a useful role in reperfusion injury during particular surgeries in which I/R-induced organ injury occurs.

Topics: Animals; Anticoagulants; Edema; Fibrin Fibrinogen Degradation Products; Glutathione; Glutathione Reductase; Interleukin-6; Intestinal Mucosa; Male; Malondialdehyde; Mesenteric Artery, Superior; Mesenteric Vascular Occlusion; Nitrates; Nitrites; Peroxidases; Protein C; Rats; Rats, Wistar; Reperfusion Injury; Tumor Necrosis Factor-alpha; Warm Ischemia; Xanthine Oxidase

This study aimed to explore the hypothesis that activated complement components contribute significantly to I/R (ischaemia/reperfusion) injury in skeletal muscle. After 50, 70 and 90 min of tourniquet ischaemia and 24 h of reperfusion, viability of the medial gastrocnemius muscle in CBA-C57BL/6 wild-type mice, assessed histochemically by reduction of NBT (Nitro Blue Tetrazolium) dye, was 60, 21 and 8% respectively. Skeletal muscle viability after 70 min of ischaemia and 24 h of reperfusion in transgenic mice expressing a combination of human CD46, CD55 and CD59, all inhibitors of complement activation, was 45% compared with 24% in ischaemic reperfused wild-type mice (P=0.008; n=6 per group). Muscle from sham-treated transgenic mice and wild-type littermates had no significant loss of viability relative to normal contralateral gastrocnemius muscle. A significant reduction in myeloperoxidase activity (a measure of neutrophil infiltration), xanthine oxidase activity (a source of free radicals) and water content (a measure of oedema) was observed in ischaemic reperfused muscle from transgenic mice compared with ischaemic reperfused wild-type muscle (P<0.05). Haematoxylin and eosin-stained histological sections also showed less damage and less apparent leucocyte infiltration in muscles from ischaemic reperfused transgenic mice than those from wild-type animals given the same degree of injury. Muscles from sham-treated transgenic and wild-type controls were almost identical with normal muscle. It is concluded that complement activation contributes to the pathogenesis of I/R injury in murine skeletal muscle, resulting in increased neutrophil infiltration into the injured muscle, increased free radical production and vascular permeability during reperfusion, and a net detrimental effect on muscle viability.

Topics: Animals; Antigens, CD; CD55 Antigens; CD59 Antigens; Complement Inactivator Proteins; Edema; Hindlimb; Humans; Membrane Cofactor Protein; Membrane Glycoproteins; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; Mice, Transgenic; Models, Animal; Muscle, Skeletal; Neutrophil Infiltration; Peroxidase; Reperfusion Injury; Xanthine Oxidase

To find the antiinflammtory constituents of Acanthopanax chiisanensis (Araliaceae) leaves, phytochemical isolation procedures were performed by activity-guided fractionation in carrageenan- and Freund's complete adjuvant (FCA) reagent-induced rat models, respectively. In the two assay system, the MeOH extract (100 and 250 mg/kg, p.o.) showed significant antiinflammtory effects. Since BuOH extract among the fractionated extracts exhibited the most potent effect, it was subjected to column chromatography to yield a main triterpene glycoside, chiisanoside (1). This compound was hydrolyzed in alkaline solution to find the biological activity of produced aglycone, chiisanogenin (1a). Oral treatment with compounds 1 and 1a produced significant antiinflammtory effects at 10 and 30 mg/kg dose, and 1a was more potent than 1. The antiiflammtory effects of the two compounds were supported by the reduction of carrageenan-induced lipid peroxidation and hydroxy radical in serum. Furthermore, treatment with 1 and 1a significantly reduced rheumatoid arthritis (RA) and C-reactive protein (CRP) factors in the rat induced by Freund's complete adjuvant reagent. Compounds, 1 and 1a, inhibited xanthine oxidase activity and increased superoxide dismutase (SOD), glutathione peroxidase and catalase indicating that both compounds scavenged reactive oxygen species (ROS).

Topics: Animals; Anti-Inflammatory Agents; Arthritis, Experimental; Arthritis, Rheumatoid; Edema; Eleutherococcus; Enzyme Inhibitors; Male; Phytotherapy; Plant Leaves; Rats; Rats, Sprague-Dawley; Xanthine Oxidase

The antiinflammatory (per os and topic) and analgesic (per os) properties of the aerial part of Proustia pyrifolia a species in danger of extinction were investigated, and the major compounds of two of its active extracts were isolated. In addition, the evaluation of cytotoxicity in three tumoral cell lines and the acute toxicity of the crude methanol extract were also assayed, together with the antioxidant activity for the different extracts of this species. The results of the evaluation of the topic antiinflammatory activities induced by arachidonic acid, and phorbol 12-myristate 13-acetate of the different extracts showed that this species possesses active constituents that could diminish cyclo-oxygenase and lipoxygenases activities, the enzymes that allow the synthesis of proinflammatory endogenous substances as prostaglandin E(2) and leukotrienes, respectively. Our results corroborate the antiinflammatory and analgesic effects of Proustia pyrifolia, and could justify its use in folk medicine for the treatment of rheumatic and gout illnesses. From bio-active extracts beta-sitosterol, quercetin and dihydroquercetin were obtained, and these compounds could explain in part the antiinflammatory, analgesic and antioxidant activities of this species. The crude methanol extract did not present acute toxicity or cytotoxic activity, however only this extract exhibited antioxidant activity.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents, Phytogenic; Antioxidants; Asteraceae; Carrageenan; Chemical Phenomena; Chemistry, Physical; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Edema; Female; Guinea Pigs; Lethal Dose 50; Magnetic Resonance Spectroscopy; Male; Mice; Pain Measurement; Plant Extracts; Solvents; Spain; Tumor Cells, Cultured; Xanthine Oxidase

Although hypothermic machine perfusion (HMP) preservation has been shown to improve organ function and to expand the organ donor pool, problems still exist with the current HMP technology for liver preservation. The present study was conducted to investigate endothelial and hepatocellular functions following extended HMP (> r =24 hr) in rat liver model.. Following 24-hour hypothermic HMP with University of Wisconsin (UW) solution or 24-hour simple cold storage (SCS), livers were reperfused with Krebs-Henseleit buffer solution at 37 degree C for 30 minutes. Hepatocyte damage and function were assessed by measuring lactate dehydrogenase (LDH) activity, bile production, and indocyanine green (ICG) extraction. Sinusoidal endothelial cell (SEC) function and permeability were determined by hyaluronic acid (HA) uptake and multiple indicator dilution (MID) method, respectively.. After 24-hour hypothermic preservation, HMP livers showed lower released LDH levels, higher bile flow rate, and greater hepatic ICG uptake compared with SCS livers. However, LDH levels became significantly higher in HMP than in SCS after 30 minutes of warm perfusion. The increased enzyme levels were accompanied by a significant increase in endothelial permeability to albumin and a decrease in hyaluronic acid uptake in HMP compared to SCS. Liver wet/dry weight ratio confirmed a greater edema in HMP livers than SCS livers.. These results suggest that 24-hour hypothermic HMP may help preservation of hepatocyte function, but endothelial cell dysfunction during the cold preservation may play a key role in hepatocyte dysfunction and parenchymal cell death upon reperfusion.

Topics: Adenosine; Albumins; Allopurinol; Animals; Bile; Cryopreservation; Edema; Endothelium; Glucose; Glutathione; Hepatocytes; Hyaluronic Acid; Insulin; L-Lactate Dehydrogenase; Liver; Liver Diseases; Male; Organ Preservation; Organ Preservation Solutions; Perfusion; Permeability; Raffinose; Rats; Rats, Sprague-Dawley; Time Factors; Tromethamine

We report a case of DRESS syndrome also called drug hypersensitivity reaction occurring a 47 years old Senegalese man who has been taking allopurinol for 3 months. That drug was prescribed for peripheric arthralgias associated to a hyperuricemia. He presented a generalised pruritus, cutaneous lesions, fever and facial oedema. On the biological examens, hyperleucocytosis with hypereosinophilia and hyperlymphocytosis associated to the presence of segmented basophiles. In addition, a hepatic cytolysis and cholestasis were documented. Liver ultrasound was normal. The hemocults were negative. These following serologies have been performed and were negative: hepatitis B and C, Epstein Barr-virus, cytomegalovirus, syphilis, toxoplasma and parvovirus B19. The anti-nuclear and anti-DNA antibodies were negative. A favourable clinical evolution was remarked after allopurinol treatment withdrawal. A desquamation occurred after 6 days and hemogram turned out to the normal as well as the hepatic tests after 2 weeks. The virologic examens performed 2 months later were unremarkable. This case point out the importance of the early diagnosis and quick withdrawal of the drug in order to prevent serious forms leading to the 10% of death.

Topics: Allopurinol; Antimetabolites; Arthralgia; Drug Eruptions; Edema; Fever; Humans; Hyperuricemia; Male; Middle Aged; Senegal; Syndrome

University of Wisconsin (UW) solution (Viaspan) is currently used to preserve organs from nonheartbeating donors. Histidine-tryptophan-ketoglutarate (HTK) solution (Custodiol) is of proven efficacy in experimental pancreas preservation, but its efficacy in combined warm ischemia (WI) and cold ischemia (CI) is unknown. The viability of HTK-preserved porcine pancreatic grafts was assessed after various periods of WI and compared with grafts flushed and preserved with UW solution.. A total of 14 pigs were used: G1 (n=4, UW) and G2 (n=4, HTK) with 15-min WI and 16-hr cold storage; G3 (n=3, UW) and G4 (n=3, HTK) with 30-min WI and 16-hr cold storage.. All animals in G1 and G2 were normoglycemic, whereas only 66% of pancreases were functioning in G3 and G4. HTK perfusion was associated with increased wet weight. Transient hyperinsulinemia was noted in all the groups on postoperative day 1 (mean range: 8.9-12.4 microU/L). Postoperative serum amylase and lipase were more pronounced in G3 and G4. However, HTK-stored grafts exhibited less evidence of biochemical pancreatitis as compared with UW-stored grafts on the first postoperative day in the group with 15-min WI. Mean K values of intravenous glucose tolerance tests on postoperative day 14 were similar in both groups. Vascular congestion was uniformly observed and was considered a typical feature of WI.. Porcine pancreatic grafts are viable after 16-hr CI following 15-min WI in this experimental nonheartbeating donor model. HTK solution seems to provide reliable graft function in this setting and to be equivalent to UW.

Topics: Adenosine; Allopurinol; Amylases; Animals; Cold Temperature; Edema; Glutathione; Graft Survival; Hot Temperature; Hyperinsulinism; Hypoglycemia; Insulin; Lipase; Models, Animal; Organ Preservation; Organ Preservation Solutions; Pancreas; Pancreas Transplantation; Raffinose; Reperfusion Injury; Swine

To find out the effect of combining allopurinol with non-steroidal anti-inflammatory drugs on carrageenan-induced rat paw edema.. The study was carried out at the College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia, over the period 1999 to 2000. Male wistar rats were randomly divided into 12-16 rats in each group. Edema was induced by subplantar injection of 0.1 ml of carrageenan (10 mg/ml) and the resulting edema volume was measured by plethysmograph, 3 hours after the injections. Saline of 0.9% (0.1 ml/100 g) was administered to the first group serving as control. The second and third groups received variable concentration of allopurinol (12.5, 25, 50 mg/kg) and tenoxicam (0.0625, 0.125, 0.25 mg/kg) 30 minutes before carrageenan injection. The fourth group received a combination of tenoxicam and allopurinol. Similar procedures were carried out with respect to diclofenac at 1.25, 2.5, 5.0 mg/kg and indomethacin at 0.25, 0.5, 1.0 mg/kg. The activities of the drugs were expressed as percentage inhibition of edema.. Pre-treatment of the rats with the 4 drugs individually resulted in dose-dependent reduction of volume of paw edema. The combination of allopurinol and diclofenac acted synergistically to reduce edema. A similar synergistic action was obtained when allopurinol was combined with indomethacin. By contrast, tenoxicam-allopurinol combination resulted in antagonistic action and produced an effect on edema, which was less than their individual inhibitory action.. Combining allopurinol with either diclofenac or indomethacin produced synergistic inhibitory action on rat's paw edema. However, tenoxicam, when combined with allopurinol, produced antagonism.

Topics: Allopurinol; Animals; Anti-Inflammatory Agents, Non-Steroidal; Carrageenan; Diclofenac; Dose-Response Relationship, Drug; Drug Interactions; Edema; Free Radical Scavengers; Hindlimb; Indomethacin; Male; Random Allocation; Rats; Rats, Wistar; Treatment Outcome

Topics: Adenosine; Allopurinol; Amylases; Animals; Disaccharides; Edema; Electrolytes; Endothelin-1; Female; Glutamates; Glutathione; Histidine; Insulin; Lipase; Mannitol; Organ Preservation; Organ Preservation Solutions; Oxygen Consumption; Pancreas; Pancreas Transplantation; Raffinose; Swine; Swine, Miniature

Topics: Adenosine; Allopurinol; Cold Temperature; Edema; Follow-Up Studies; Glutathione; Graft Rejection; Humans; Insulin; Organ Preservation; Organ Preservation Solutions; Pancreas; Pancreas Transplantation; Postoperative Complications; Raffinose; Safety; Time Factors; Treatment Failure; Treatment Outcome

We measured the amount of edema and the free radical production in burn-injured skin and the serum histamine levels, as well as changes in dermal interstitial fluid pressure.. Thirty-six Wistar rats with 20% total body surface area burns of different depth were resuscitated by lactated Ringer's solution intravenously. The rats were divided into a deep burn (DB) group (n = 12), a superficial dermal burn (SDB) group (n = 12), and a sham burn (Sham) group (n = 12). Dermal interstitial fluid hydrostatic pressure (Pif), total skin water and xanthine oxidase activity, and serum histamine levels were measured until 60 minutes postburn.. In the DB group, dermal Pif significantly fell to -35.9 +/- 11.0 and -40.9 +/- 7.0 mm Hg at 10 and 15 minutes postburn, respectively (p < 0.05); it returned to preburn values at 50 minutes postburn. In the SDB group, dermal Pif was slightly negative but did not markedly change. Total skin water was significantly higher than that of the DB and the Sham groups; however, in the SDB group, serum histamine and dermal xanthine oxidase were significantly higher than in the DB group at 15, 30, and 45 minutes postburn (p < 0.05).. The fluid-resuscitated DB produced a more negative dermal Pif than the SDB, but less dermal edema. In contrast, the SDB appeared to mainly generate dermal edema formation by wound free radical production and serum histamine release. The dermal Pif is one of the factors associated with edema formation immediately after deep burns. However, an increase in vascular permeability associated with oxygen radical production plays a more important role in dermal edema formation than does dermal Pif.

Topics: Animals; Body Water; Burns; Edema; Extracellular Space; Free Radicals; Histamine; Rats; Rats, Wistar; Xanthine Oxidase

Reactive oxygen species have been shown to play an important role in the pathogenesis of lung injury. This study was designed to clarify the role of intrapulmonary neutrophils in the development of xanthine/xanthine oxidase (X/XO)-induced lung injury in isolated buffer-perfused rabbit lungs. We measured microvascular fluid filtration coefficient (K(f)) and wet-to-dry weight ratio to assess lung injury. X/XO induced a significant increase in K(f) and wet-to-dry weight ratio in neutrophil-replete lungs, whereas the lung injury was attenuated in neutrophil-depleted lungs. A neutrophil elastase inhibitor, ONO-5046, also attenuated the lung injury. In addition, X/XO induced a transient pulmonary arterial pressure (P(pa)) increase. The thromboxane inhibitor OKY-046 attenuated the P(pa) increase but did not alter the increase in permeability. Neutrophil depletion reduced the K(f) increase but had no effect on the P(pa) increase. These results suggest that intrapulmonary neutrophils activated by X/XO play a major role in development of the lung injury, that neutrophil elastase is involved in the injury, and that the X/XO-induced vasoconstriction is independent of intrapulmonary neutrophils.

Topics: Animals; Blood Pressure; Capillary Permeability; Drug Combinations; Edema; In Vitro Techniques; Lung; Lung Diseases; Neutrophils; Oxidants; Peroxidase; Pulmonary Artery; Pulmonary Circulation; Rabbits; Vasoconstriction; Xanthine; Xanthine Oxidase

Studies of myocardial edema and diastolic dysfunction in rat heart transplantation have been flawed by ischemic injury. This study uses improved methods to prevent ischemic contracture.. Hearts of 30 ACI rats were transplanted into the abdomen of Lewis rats by use of cold University of Wisconsin solution for improved preservation. Left ventricular diastolic properties were expressed as volume at standardized pressure intervals.. On posttransplantation day 3, mean left ventricular volume at 15 mm Hg in allografts (290 +/- 9 microl, SEM) was not significantly different vs isografts (299 +/- 32 microl), allografts on day 0 (337 +/- 28 ml) or day 1 (324 +/- 20 microl), or native hearts (334 +/- 19 microl). However, volume was reduced to 173 +/- 17 microl on day 4 and to 70 +/- 23 microl on day 5 (p < 0.05). Similar findings were obtained for volume at 5 and 10 mm Hg. Allograft myocardial water content on day 3, 76.3% +/- 5%, similar to allografts on day 0 and 1 and to isografts on day 3, increased to 77.6% +/- 8% on day 4 (NS) and 79.4% +/- 6% on day 5 (p < 0.05 vs day 0). Histologically, rejection in allografts was mild on day 3, moderate on day 4, and severe on day 5.. Reduced left ventricular filling volume during rejection is only partially explained by edema. Abnormalities of diastolic properties previously attributed to the unloaded state of nonworking heart models may actually reflect inadequate peritransplantation myocardial protection.

Topics: Adenosine; Allopurinol; Animals; Cardiomyopathies; Cardioplegic Solutions; Diastole; Edema; Glutathione; Graft Rejection; Heart Transplantation; Insulin; Male; Organ Preservation; Organ Preservation Solutions; Raffinose; Rats; Rats, Inbred ACI; Rats, Inbred Lew; Transplantation, Heterotopic; Ventricular Dysfunction, Left

Ethanolic extracts from 15 plant species, representing eight different families, used in traditional medicine in Ecuador were evaluated for antiinflammatory and antioxidant activities. Conyza floribunda, Eupatorium articulatum, Bonafousia longituba, Bonafousia sananho, Tagetes pusilla and Piper lenticellosum extracts showed a significant antiinflammatory activity in vivo in the carrageenan-induced paw oedema model in mice. The extracts were also tested in vitro for their ability to inhibit lipid peroxidation and to scavenge superoxide and hydroxyl radicals. E. articulatum extract possesses both activities. Baccharis trinervis, E. articulatum and Phytolacca rivinoides extracts were active as antioxidants.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Ecuador; Edema; Ethanol; Female; Free Radical Scavengers; Hydroxyl Radical; In Vitro Techniques; Lipid Peroxidation; Male; Medicine, Traditional; Mice; Microsomes; Microsomes, Liver; Plant Extracts; Plants, Medicinal; Rats; Rats, Wistar; Superoxides; Xanthine Oxidase

The University of Wisconsin solution has been proven to be effective for prolonged heart preservation. However, 24-hour heart preservation by simple cold immersion in University of Wisconsin solution has been disappointing. We have performed hypothermic low-pressure continuous coronary perfusion with oxygenated University of Wisconsin solution for experimental prolonged heart preservation. However, the high potassium concentration of University of Wisconsin solution combined with prolonged ischemia has detrimental effects on endothelial function, which increases coronary tone during preservation and after reperfusion. The severe vasoconstriction and tissue edema result in damage to the coronary microcirculation. The purpose of this study was to determine whether hypothermic low-pressure continuous coronary perfusion technique with oxygenated University of Wisconsin solution containing a selective endothelin-A receptor antagonist (FR139317) would increase the effectiveness of the perfusion technique and improve postischemic cardiac function, both minimizing tissue edema and suppressing vasoconstriction.. Preischemic and postischemic cardiac function of isolated rabbit hearts was evaluated with a Langendorff apparatus. The hearts were divided into three groups (n = 7 each): group I (hypothermic low-pressure continuous coronary perfusion with University of Wisconsin solution), group II (hypothermic low-pressure continuous coronary perfusion with oxygenated University of Wisconsin solution), and group III (hypothermic low-pressure continuous coronary perfusion with oxygenated University of Wisconsin solution containing 10 mg/L of FR139317). Preservation was performed for 24 hours. The initial perfusion pressure for continuous coronary perfusion was set at 5 mm Hg. Measurement of percentage of tissue water content and ultrastructural examination of the myocardium was then performed. In groups I, II, and III, the perfusion pressures at the end of the 24-hour preservation period increased from 5 mm Hg to 12.2 +/- 2.5, 8.1 +/- 1.3, and 5.4 +/- 0.8 mm Hg (p < 0.05), respectively. Percent recovery rate of cardiac output was 56.6 +/- 2.8, 82.3 +/- 8.2, and 93.3 +/- 6.0 (p < 0.05), respectively. And percent recovery rate of coronary flow was 55.5 +/- 8.1, 80.0 +/- 8.0, and 94.3 +/- 9.4 (p < 0.05), respectively. A significant inverse correlation was found between continuous coronary perfusion pressure at the end of preservation and the recovery rate of cardiac output (r = 0.85, p < 0.05). Tissue water content was significantly higher in group I than in groups II and III. These effects were inhibited by oxygenation of the University of Wisconsin solution (group II) and by the addition of the selective endothelin-A receptor antagonist (FR139317) (group III). Damage to coronary circulation was reduced by oxygenation and the addition of endothelin-A receptor antagonist during prolonged heart preservation.. We concluded that hypothermic low-pressure continuous coronary perfusion technique with oxygenated UW solution containing endothelin-A receptor antagonist (FR139317) maintained coronary circulation by suppressing tissue edema and vasoconstriction during preservation, which improved postischemic functional recovery.

Topics: Adenosine; Allopurinol; Animals; Azepines; Blood Pressure; Body Water; Cardiac Output; Cardioplegic Solutions; Coronary Circulation; Cryopreservation; Edema; Endothelin Receptor Antagonists; Glutathione; Heart Transplantation; Hypothermia, Induced; Indoles; Insulin; Ischemia; Microcirculation; Myocardial Contraction; Myocardium; Organ Preservation; Organ Preservation Solutions; Oxygen; Rabbits; Raffinose; Reperfusion; Time Factors; Vasoconstriction

The effectiveness of University of Wisconsin (UW) and University of Pittsburgh (UP) solutions for the preservation of rat hearts was compared. Lewis rat hearts were preserved with UW (group A, n = 45) or UP (group B, n = 45) solution for 0 or 24 h and then transplanted heterotopically into the recipients' abdomen. Ten recipients in each group were observed to obtain 1-week graft survival rates. Tissue water content and tissue content of adenine nucleotides were measured 2 h after transplantation in six grafts from each group. Six hearts preserved for 0 h and seven hearts preserved for 24 h were taken from each group 24 h after grafting for histopathology. The 1-week graft survival rates of groups A24 and B24 were 60% and 10%, respectively. In the 24-h preserved grafts, adenosine triphosphate (ATP) and energy charge [(ATP + adenosine diphosphate/2)/(ATP + adenosine diphosphate + adenosine monophosphate)] of groups A and B were 0.972 +/- 0.165 and 0.200 +/- 0.123 mg/g wet tissue (P < 0.05) and 74.4% and 61.1% (P < 0.05), respectively. The tissue water content of group A24 was 71.7%, whereas that of group B24 was 74.1% (P < 0.05). Histopathology revealed more severe muscle edema and necrosis and infiltration of polymorphonuclear cells in group B24 than in group A24. We conclude that UW solution is more appropriate for rat heart preservation than UP solution.

Topics: Abdomen; Adenine Nucleotides; Adenosine; Allopurinol; Animals; Body Water; Cardioplegic Solutions; Edema; Energy Metabolism; Glutathione; Graft Survival; Heart; Heart Transplantation; Insulin; Male; Myocardium; Organ Preservation; Organ Preservation Solutions; Raffinose; Rats; Rats, Inbred Lew; Transplantation, Heterotopic

Topics: Adenosine; Allopurinol; Analysis of Variance; Animals; Cardioplegic Solutions; Coronary Vessels; Edema; Glutathione; Heart; Heart Arrest, Induced; Insulin; Magnetic Resonance Spectroscopy; Male; Organ Preservation; Organ Preservation Solutions; Perfusion; Polyethylene Glycols; Raffinose; Rats; Rats, Wistar; Time Factors; Ventricular Function, Left

Topics: Adenosine; Adolescent; Adult; Allopurinol; Amylases; Edema; Female; Glutathione; Humans; Insulin; Magnetic Resonance Imaging; Male; Middle Aged; Organ Preservation; Organ Preservation Solutions; Pancreas Transplantation; Pancreatic Diseases; Raffinose; Time Factors; Tissue Donors

We investigated the effects of D-neopterin (NP) and its reduced form, 5,6,7,8-tetrahydro-D-neopterin (NPH4), in two models of ischemia-reperfusion injury, i.e., ischemic paw edema in mice and gastric ischemia in rats. In ischemic paw edema, iv administration of either NP or NPH4 more potently inhibited the increase of paw thickness after release from ischemia than did administration of superoxide dismutase plus catalase or allopurinol. In gastric ischemia, NP and NPH4 also significantly suppressed the formation of gastric mucosal erosions. Lipid peroxidation in the stomach was increased by ischemia-reperfusion treatment, and the increase was inhibited by the administration of NP or NPH4. The minimum dose of NPH4 required to suppress the gastric ischemic injury in this experiment was 0.3 mg/kg of body weight. These results suggest that neopterin may be effective as a protective agent against ischemia-reperfusion injury, in which active oxygen species are believed to play a major role.

Topics: Allopurinol; Animals; Biopterins; Catalase; Disease Models, Animal; Dose-Response Relationship, Drug; Edema; Gastric Mucosa; Lipid Peroxidation; Male; Mice; Neopterin; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Reperfusion Injury; Superoxide Dismutase

The role of eicosanoid metabolism and its relationship with nitric oxide production in the ischemia-reperfusion associated with pancreas transplantation in the rat is explored in this study. Twenty-six male Sprague-Dawley rats were randomized into 3 groups, as follows: group 1, control animals not surgically manipulated; group 2, pancreas transplantation, after 12 hr of organ preservation in University of Wisconsin solution; group 3, same as group 2 but with administration of NG-nitro-L-arginine methyl ester (a nitric oxide synthase inhibitor) (10 mg/kg) before organ revascularization. The results show posttransplantation increases in edema and in 6-keto-prostaglandin F1 alpha (x1.9), thromboxane B2 (x4), and prostaglandin E2 (x5) levels in pancreatic tissue. Nitric oxide synthase inhibition reversed the increases in edema and eicosanoid production, which suggests that eicosanoid generation in the recipient rat would be mediated, in part, through a nitric oxide-dependent mechanism.

Topics: Adenosine; Allopurinol; Animals; Arginine; Dinoprostone; Edema; Glutathione; Insulin; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide; Organ Preservation; Organ Preservation Solutions; Pancreas Transplantation; Prostaglandins F; Raffinose; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Thromboxane B2

Topics: Adenosine; Adolescent; Adult; Allopurinol; Edema; Glutathione; Humans; In Vitro Techniques; Insulin; Magnetic Resonance Imaging; Organ Preservation; Organ Preservation Solutions; Pancreas; Pancreas Transplantation; Pancreatic Diseases; Raffinose; Time Factors; Tissue Donors; Water

The aim of this study was to explore whether intraperitoneal administration of ascorbic acid (AA) at a dose of 500 mg/kg, once a day for 3 following days, affected the peroxidase (PO) activity in inflamed feet of mice. The foot inflammatory reaction induced by the carrageenan (CAR), n-formyl-methionyl-leucyl-phenylalanine (FMLP) and xanthine-xanthine oxidase was accompanied by suppression of PO activity. Administration of AA, having no effect on the degree of foot oedema, skin temperature and microscopic picture of tissue specimens significantly enhanced the decline in PO activity provoked by inflammatory agents. This activity decreased 2.0-, 1.6- and 1.9-fold (p < 0.001, p < 0.01, p < 0.05) when inflammatory response was induced with FMLP, CAR and X-XO, respectively. Also in vitro AA (50-100 micrograms/ml) inhibited PO activity of leukocyte lysate and foot extract obtained from untreated animals. In conclusion we found that AA, having no effect on inflammatory response, significantly enhanced inhibition of PO activity in inflamed tissues in mice which could be a result of direct action of AA on the enzyme molecule.

Topics: Animals; Ascorbic Acid; Carrageenan; Edema; Foot; Inflammation; Male; Mice; Mice, Inbred BALB C; N-Formylmethionine Leucyl-Phenylalanine; Peroxidase; Skin Temperature; Xanthine; Xanthine Oxidase; Xanthines

Oxygen free radicals and prostaglandins are implicated in the pathophysiology of acute pancreatitis, although their mechanisms of action remain unclear. We have studied the effect of administration of exogenous 16,16-dimethyl prostaglandin E2 and superoxide dismutase on oxygen free radical production in acute pancreatitis. For this purpose, five experimental rat groups were studied: group I, control; group II, sodium taurocholate-induced acute pancreatitis; group III, same as group II but with previous administration of 16,16-dimethyl prostaglandin E2; group IV, same as group II but with previous administration of indomethacin; and group V, same as group II but with previous administration of superoxide dismutase. In sodium taurocholate-treated rats, xanthine dehydrogenase is completely converted to xanthine oxidase within the first 5 min with subsequent oxygen free radical production while in 16,16-dimethyl prostaglandin E2-treated rats this enzyme transformation does not occur. In the superoxide dismutase-treated group xanthine oxidase activation is partially prevented. These data suggest that xanthine oxidase is the main source of oxygen free radicals, which contribute to extending the cellular damage in sodium taurocholate-induced acute pancreatitis.

Topics: 16,16-Dimethylprostaglandin E2; Acute Disease; Animals; Edema; Enzyme Activation; Free Radicals; Indomethacin; Lipase; Lipid Peroxidation; Male; Pancreatitis; Rats; Rats, Wistar; Reactive Oxygen Species; Superoxide Dismutase; Taurocholic Acid; Xanthine Dehydrogenase; Xanthine Oxidase

There has been great interest stimulated by reports on factors influencing the survival of skin flaps which possess only venous inflow and outflow, i.e., venous flaps. The present study serially (Days 1, 2, and 4 postoperatively) observed several biochemical factors which might affect flap survival. ATP levels were measured to assess endogenous energy stores, malonyldialdehyde (MDA) and xanthine oxidase (XO) to estimate free radical production, superoxide dismutase (SOD) to quantify antioxidant defenses, and edema to measure inflammatory changes. Eighteen thighs on nine dogs were assigned randomly to one of three groups: full-thickness skin grafts, flaps based solely on the saphenous artery and vein (AV flaps), or flaps based solely on the saphenous vein (venous flaps). These were regarded as being mostly ischemic, totally perfused, and partially ischemic, respectively. Control skin biopsies were obtained adjacent to surgical sites. AV flaps and control skin were similar in all respects. Venous flaps compared with skin grafts were significantly less edematous (P less than 0.01) had less MDA and XO (P less than 0.05), but no significant differences in SOD and ATP levels. However venous flaps had significantly less ATP than AV flaps (P less than 0.01). Thus venous flaps survive despite depletion of ATP levels. These results suggest that decreased free radical production and lessened edema may be important factors in promoting ultimate survival of venous flaps.

Topics: Adenosine Triphosphate; Analysis of Variance; Animals; Arteries; Dogs; Edema; Malondialdehyde; Saphenous Vein; Skin; Skin Transplantation; Superoxide Dismutase; Surgical Flaps; Time Factors; Vascular Surgical Procedures; Xanthine Oxidase

Topics: Adenine Nucleotides; Allopurinol; Animals; Creatinine; Edema; Endothelium; Free Radicals; Kidney; Kidney Transplantation; Organ Preservation; Oxygen; Rats; Rats, Inbred Lew; Superoxide Dismutase; Xanthine Oxidase

In this study rat epigastric island flaps were used as a model to investigate selected tissue biochemical changes occurring during secondary ischemia. It was hypothesized that free radical damage, depletion of free radical scavengers, depletion of ATP, and increased edema might explain differences in flap survival between partial (venous obstruction) and total (arteriovenous obstruction) ischemia and decreased flap survival with increasing ischemia time. Flaps were given 2 hr or primary ischemia, 8 hr of normal perfusion, then secondary ischemia of 0, 2, 4, 8, or 12 hr with either arteriovenous obstruction or venous obstruction. Biochemical analysis of the skin was performed after 0, 24, or 96 hr reperfusion. Only minor differences were found between arteriovenous and venous ischemia for any of five biochemical parameters, despite a previous finding that venous ischemic flaps are more susceptible to necrosis. Levels of xanthine oxidase and malonyldialdehyde (both indices of free radical generation) increased with ischemia time. Levels of superoxide dismutase (a free radical scavenger) correspondingly decreased. Tissue levels of ATP decreased after ischemia and recovered to normal for shorter but not for longer ischemia times after 96 hr of reperfusion in parallel with flap survival. Edema increased immediately after the ischemic insult but decreased once the tissue became necrotic. These results imply roles for free radicals, ATP, and edema in secondary ischemia, but do not distinguish between arteriovenous and venous secondary ischemia.

Topics: Adenosine Triphosphate; Animals; Constriction; Edema; Ischemia; Male; Malondialdehyde; Rats; Rats, Inbred Strains; Reperfusion Injury; Superoxide Dismutase; Surgical Flaps; Xanthine Oxidase

The excessive generation of free radicals is thought to be one of the major mechanisms leading to tissue injury in various pathological conditions, including ischemia, inflammation, and trauma. Conversion of xanthine dehydrogenase (XDH) to xanthine oxidase (XO) contributes to the formation of superoxide, an oxygen radical. We measured XDH and XO activity using a newly developed fluorometric assay in an experimental spinal cord injury model in rats. XO activity increased by more than 100% 4 h after spinal cord trauma. Total (XDH + XO) activity also increased by 96% during the same period. Allopurinol, an inhibitor of XO (100 mg/kg/day x 2 days, i.p.), completely inhibited plasma and spinal cord XO activity but did not affect posttraumatic edema determined by water content or polymorphonuclear (PMN) cell infiltration reflected by myeloperoxidase (MPO) activity in traumatized spinal cord. These results indicate that XDH conversion to XO may not be the major mechanism of oxygen radical formation in the pathogenesis of vasogenic edema or inflammatory response in this experimental spinal cord injury model in rats.

Topics: Allopurinol; Animals; Body Water; Edema; Neutrophils; Peroxidase; Rats; Rats, Inbred Strains; Spectrometry, Fluorescence; Spinal Cord; Spinal Cord Injuries; Xanthine Dehydrogenase; Xanthine Oxidase

1. Nilvadipine (FK 235, FR 34235) suppressed ischemia (20 min)-reflow (20 min)-induced paw edema of mice (ED30:0.4 mg/kg i.v. and 2 mg/kg p.o.). Other calcium entry blockers of dihydropyridine-type also suppressed the edema, but 30-fold higher doses were required. 2. Oral dosing of nilvadipine suppressed carrageenan-induced paw edema (ED30:15 mg/kg in rats and 20 mg/kg in mice) at a potency corresponding to that of an anti-inflammatory drug, ibuprofen. Nifedipine, nicardipine and nimodipine resulted in a suppression of 30% only with 100 mg/kg oral dosing in rats. Nitrendipine, diltiazem and verapamil were without effect. 3. Nilvadipine inhibited superoxide radical (O-2production from xanthine oxidase (XOD) both with lactate dehydrogenase + NADH method and cytochrome c method (IC50:90 and 100 micrograms/ml, respectively). Nifedipine and nicardipine showed some inhibition, but the other calcium entry blockers failed to inhibit significantly even at 320 micrograms/ml. As uric acid formation was not reduced by the tested drugs, the inhibitory action might be due to their O-2scavenging effects. 4. Superoxide production of neutrophils from casein-induced peritoneal fluid in rats was most strongly inhibited by nilvadipine when the cells were stimulated by a calcium ionophore, A23187 (IC50:4 micrograms/ml). Inhibition by this drug when stimulated by f-methonyl-leucyl-phenylalanine and phorbol myristate acetate was less effective (IC50:20 and 30 micrograms/ml, respectively). Nifedipine and nicardipine inhibited neutrophil O-2production at higher concentrations (30-200 micrograms/ml) with all stimulants. Inhibitory actions by other drugs were weak. 5. Triggering of atherosclerosis depends largely on the oxidative stress on blood vessels after recently established concept.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Calcimycin; Carrageenan; Edema; Free Radicals; Ischemia; L-Lactate Dehydrogenase; Male; Mice; Mice, Inbred Strains; N-Formylmethionine Leucyl-Phenylalanine; Neutrophils; Nifedipine; Rats; Rats, Inbred Strains; Superoxides; Tetradecanoylphorbol Acetate; Xanthine Oxidase

Oxygen-derived free radicals are thought to injure the ischemic heart during coronary microvascular embolization.. To test this idea, microspheres (15 microns in diameter) were repetitively administered into the left anterior descending coronary artery to cause microvascular embolization in dogs. Myocardial contractile and metabolic dysfunctions were significantly attenuated after treatments with recombinant human superoxide dismutase, an acyl derivative of ascorbic acid (CV3611, 2-O-octadecylascorbic acid), and xanthine oxidase inhibitor (allopurinol). The free radical scavengers and inhibitor enhanced the coronary hyperemic flow response during embolization, and the total number of microspheres causing maximal embolization was increased by these drugs. When 8-phenyltheophylline was additionally administered with superoxide dismutase, these beneficial effects were abolished, indicating that coronary effects of these drugs may be due to increased release of adenosine during coronary microvascular embolization.. We conclude that oxygen radicals worsen the ischemic injury in coronary microembolization.

Topics: Allopurinol; Animals; Ascorbic Acid; Body Water; Cardiomyopathies; Coronary Disease; Dogs; Edema; Embolism; Free Radical Scavengers; Free Radicals; Microcirculation; Microspheres; Oxygen; Superoxide Dismutase; Theophylline

Pyrroloquinoline quinone (PQQ) inhibited the chemiluminescence (CL) from mouse peritoneal cells initiated by zymosan, carrageenin and N-formyl-methionyl-leucyl-phenylalanine and CL generated by the xanthine-xanthine oxidase reaction and the lipid peroxidation in the rat brain homogenate. The inhibitory activity of PQQ was more potent than that of idebenone, alpha-tocopherol and ascorbic acid in all the three assay systems. In the xanthine-xanthine oxidase reaction, PQQ had no effect on the formation of uric acid at the concentration of CL inhibition. These results suggest that PQQ might have a radical scavenger-like activity. Structure-activity relationship of PQQ and its six related compounds showed that the 7- and 9-carboxyl groups of PQQ as well as the orthoquinone structure are responsible for the radical scavenger-like activity. In addition, the -NH group in the pyrrole ring of PQQ seemed to be essential for the antilipid peroxidative activity in the rat brain homogenate. When administered i.p., PQQ inhibited the development of 0.1% carrageenin-induced paw edema in rats. These results suggest that PQQ might have therapeutic effects on various diseases, of which development or exacerbation has been known to be associated with radical oxygens.

Topics: Animals; Brain; Carrageenan; Edema; Lipid Peroxidation; Luminescent Measurements; Male; Mice; Mice, Inbred ICR; N-Formylmethionine Leucyl-Phenylalanine; Peritoneal Cavity; PQQ Cofactor; Quinolones; Rats; Rats, Inbred Strains; Structure-Activity Relationship; Xanthine; Xanthine Oxidase; Xanthines; Zymosan

We measured lipid peroxidation of plasma, lung, and liver in anaesthetized sheep after third-degree burns involving 30% of total body surface. Animals were resuscitated to baseline filling pressures with lactated Ringer's solution and killed 10 hours after burn. Six sheep were pretreated with ibuprofen (12.5 mg/kg) and five with allopurinol (50 mg/kg). We used conjugated dienes and malondialdehyde as measures of lipid peroxidation. Circulating conjugated dienes increased from a baseline of 0.48 +/- 0.06 to 0.64 +/- 0.05 after burn, while protein-rich burn tissue lymph flow increased up to eightfold. We also noted a significant increase in lung tissue malondialdehyde from 45 +/- 4 to 60 +/- 6 nmol/gm and liver malondialdehyde from 110 +/- 20 to 271 +/- 34 nmol/gm along with increased tissue neutrophil sequestration. Ibuprofen attenuated lung-tissue malondialdehyde but had no effect on lung inflammation, circulating lipid peroxides or burn edema, indicating that ibuprofen most likely decreased O2 radical release in lung tissue by the already-sequestered neutrophils. Allopurinol, possibly via xanthine oxidase inhibition, markedly attenuated burn QL and circulating lipid peroxides and prevented all pulmonary lipid peroxidation and inflammation, indicating that release of oxidant from burn tissue was in part responsible for local burn edema, as well as distant inflammation and oxidant release, the latter most likely from complement activation. Neither antioxidant decreased lipid peroxidation in the liver; this indicates that its mechanism of production was different from that seen in burn tissue, in plasma, or in the lung. An ischemic event resulting from a selective decrease in splanchnic blood flow may be the cause of the liver changes.

Topics: Allopurinol; Animals; Burns; Disease Models, Animal; Edema; Ibuprofen; Inflammation; Lipid Peroxidation; Liver; Lung; Malondialdehyde; Neutrophils; Oxygen Consumption; Reference Values; Sheep

These studies were designed to assess pathophysiologic factors responsible for increased vascular permeability occurring in rat skin that has been thermally injured in vivo. Under the conditions employed, permeability changes and edema formation progressed over time, with peak changes occurring 60 minutes after thermal trauma. The plasma of thermally injured rats showed dramatic increases in levels of xanthine oxidase activity, with peak values appearing as early as 15 minutes after thermal trauma. Excision of the burned skin immediately after thermal injury significantly diminished the increase in plasma xanthine oxidase activity. The skin permeability changes were attenuated by treatment of animals with antioxidants (catalase, superoxide dismutase [SOD], dimethyl sulfoxide [DMSO], dimethylthiourea [DMTU]) or an iron chelator (deferoxamine), supporting the role of oxygen radicals in the development of vascular injury as defined by greatly increased vascular permeability. Studies employing laser Doppler velocimetry in thermally injured skin revealed a pronounced and sustained decrease in blood flow after thermal trauma, a pattern not affected by protective interventions. The failure of neutrophil depletion to protect against the vascular permeability changes and the protective effects of the xanthine oxidase inhibitors (allopurinol and lodoxamide tromethamine) suggest that xanthine oxidase is the most likely source of the oxygen radicals involved in edema formation. Lodoxamide was found to have some hydroxyl radical (HO.) scavenging ability (greater than that of allopurinol) but no iron chelating activity. Some of the protective effects of lodoxamide and allopurinol may be linked to their HO. scavenging ability. These data suggest that, in this model of thermal trauma, vascular injury defined by increased vascular permeability is, in part, related to the activation of xanthine oxidase and the generation of toxic oxygen metabolites that damage microvascular endothelial cells.

Topics: Animals; Burns; Edema; Enzyme Inhibitors; Free Radicals; Hydroxides; Hydroxyl Radical; Microcirculation; Oxygen; Rats; Skin; Xanthine Oxidase

The pathogenesis of burn edema in the skin of rats appears to be related to a role for histamine, xanthine oxidase and oxygen radicals. Histamine and its metabolic derivatives increase the catalytic activity of xanthine oxidase (but not xanthine dehydrogenase) in rat plasma and in rat pulmonary artery endothelial cells. In thermally injured rats levels of plasma histamine and xanthine oxidase rise in parallel, in association with increases in uric acid. Burn edema is greatly attenuated by treatment of rats with the mast cell stabilizer, cromolyn, by complement depletion and by treatment with the H2 receptor antagonist, cimetidine, but is unaffected by neutrophil depletion. These studies suggest the following pathogenesis of burn edema: thermal trauma causes complement activation with anaphylatoxin release and mast cell secretion of histamine, leading to enhancement of xanthine oxidase activity and increased production of oxygen radicals which damage endothelial cells.

Topics: Animals; Burns; Cimetidine; Complement Inactivator Proteins; Complement System Proteins; Cromolyn Sodium; Edema; Elapid Venoms; Endothelium, Vascular; Histamine; Histamine H1 Antagonists; Hydroxides; Hydroxyl Radical; Kinetics; Male; Radioimmunoassay; Rats; Skin; Superoxides; Uric Acid; Xanthine Oxidase

The role of oxygen-derived free radicals in the pathogenesis of acute pancreatitis was studied by evaluating the effects of catalase, allopurinol, and dimethylsulfoxide on diet-induced acute hemorrhagic pancreatic necrosis in mice. The mortality rate and degree of hyperamylasemia associated with this model of pancreatitis were reduced by catalase but a similar result followed the administration of heat-denatured catalase, suggesting that the apparent protective effect of catalase was not the result of reductions in free radical levels. Neither allopurinol nor dimethylsulfoxide reduced mortality or degree of hyperamylasemia. The increased pancreatic content of amylase and the necrosis that characterize this model of pancreatitis were not altered by any of the agents tested. In contrast, both allopurinol and dimethylsulfoxide reduced peripancreatic edema formation, suggesting that edema, but not the other features that characterize this model of pancreatitis, may result from generation of oxygen-derived free radicals.

Topics: Acute Disease; Allopurinol; Amylases; Animals; Catalase; Choline Deficiency; Diet; Dimethyl Sulfoxide; Edema; Ethionine; Female; Free Radicals; Hemorrhage; Mice; Necrosis; Oxygen; Pancreatitis

Topics: Acute Disease; Allopurinol; Animals; Ceruletide; Edema; Esters; Gabexate; Guanidines; Male; Pancreatitis; Rats; Rats, Inbred Strains; Trypsin Inhibitors

We evaluated whether supplemental pharmacologic interventions that altered formation or degradation of reactive oxygen metabolites, when added to hypothermic crystalloid cardioplegic solution (procaine-free St. Thomas' Hospital solution), alter postischemic function of isolated rabbit hearts. Hypoxic, substrate-free cardioplegic solutions cooled to 27 degrees C were perfused through isolated rabbit hearts for 5 minutes before and after an uninterrupted 2 hour period of global ischemia at 27 degrees C. Hearts were then reperfused with standard buffer for 1 hour at 37 degrees C. In some experiments, the cardioplegic solution was supplemented with the following: superoxide dismutase (30 micrograms/ml; degrades superoxide anion); catalase (1.7 micrograms/ml; degrades hydrogen peroxide); allopurinol (1 mmol/L; inhibits xanthine oxidase); or deferoxamine (Desferal, 0.5 mmol/L; selectively chelates ferric iron). Postreperfusion contractile parameters of supplemented hearts, including left ventricular pressure development and its first derivative, left ventricular compliance, spontaneous heart rate, and coronary vascular resistance, were statistically compared to data obtained from hearts arrested with unsupplemented cardioplegic solution. Catalase supplementation provided statistically significant improvement of most functional parameters; somewhat less protection was obtained with allopurinol. Deferoxamine provided little added protection except for the ability to prevent ischemia-induced increases of coronary vascular resistance. There was no evidence of added protection by superoxide dismutase. The data suggest that an important component of ischemia-induced cardiac cell damage in an asanguineous setting is hydrogen peroxide-dependent, and interventions that either inhibit production of superoxide anion or degrade hydrogen peroxide offer best protection. They may be clinically efficacious additives to crystalloid cardioplegic solutions.

Topics: Allopurinol; Animals; Bicarbonates; Blood Pressure; Calcium Chloride; Catalase; Coronary Circulation; Coronary Disease; Deferoxamine; Diastole; Edema; Heart Arrest, Induced; Heart Rate; Magnesium; Myocardial Contraction; Myocardial Revascularization; Myocardium; Potassium Chloride; Rabbits; Sodium Chloride; Superoxide Dismutase

Recent studies examining the effect of allopurinol on bacterial killing by leukocytes [Tubaro et al., Biochem. Pharmac. 29, 3018 (1980); Tritsch and Neiswander, Life Sci. 32, 1359 (1983)] have been interpreted by those authors as proof that xanthine oxidase is the major superoxide producing enzyme in activated leukocytes. To test the assertion that xanthine oxidase is involved in the production of superoxide by activated human neutrophils, the xanthine oxidase content of neutrophils was measured, and the effect of allopurinol on neutrophil functions, including superoxide production, was studied. Neutrophils were found to contain a level of xanthine oxidase insufficient to account for the flux of superoxide associated with neutrophil activation. Allopurinol did not inhibit superoxide production induced by opsonized zymosan, phorbol myristic acetate, or formylmethionylleucylphenylalanine. Furthermore, neither chemotaxis nor degranulation was affected by allopurinol. Allopurinol was also found ineffective in blocking superoxide-mediated carrageenan-induced foot edema in the rat. These studies are interpreted as evidence that xanthine oxidase is not a major superoxide-generating system in activated neutrophils as has been suggested by others.

Topics: Allopurinol; Animals; Carrageenan; Drug Interactions; Edema; Humans; N-Formylmethionine Leucyl-Phenylalanine; Neutrophils; Rats; Superoxides; Tetradecanoylphorbol Acetate; Xanthine Oxidase

Topics: Allopurinol; Animals; Catalase; Edema; Free Radicals; Hypoxanthines; Inflammation; Male; Oxygen; Rats; Superoxide Dismutase; Time Factors; Xanthine Oxidase

Total starvation is effective for acute weight reduction in obesity. However, in 200 patients, most of whom also had internal diseases, 8% exhibited sometimes severe complications, i.e. reversible cerebral ischemia in 3 hypertensive patients when the blood pressure was lowered to the normal range by natriuresis of fasting; breakdown of water and electrolyte homeostasis with circulatory collapse, vomiting and vertigo; acute crises of paroxysmal nocturnal hemoglobinuria and porphyria respectively and increase of transaminases up to 200 mu/ml, or cardiac arrhythmias. Relative (?) contraindications for total fasting appear to be clinical sings of arteriosclerosis such as vascular bruits, angina pectoris and intermittent claudication. In case of doubt, the method should only be used in hospital.

Topics: Acetone; Adult; Allopurinol; Arrhythmias, Cardiac; Diet, Reducing; Edema; Female; Humans; Ischemic Attack, Transient; Male; Middle Aged; Obesity; Spironolactone; Starvation; Transaminases; Urea; Water-Electrolyte Imbalance

Topics: Allopurinol; Animals; Anti-Inflammatory Agents; Arthritis; Edema; Kaolin; Male; Models, Biological; Pleurisy; Rats; Turpentine; Xanthine Oxidase