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PubMed1981

Effects of some hypolipidemic drugs on biochemical values and on hepatic peroxisomal enzymes of normolipemic rat.

Effects of vitamin B2-butyrate, nicomol, ML-236B, KF 1492 and pantethine, which are hypolipidemic drugs, on biochemical values and on hepatic peroxisomal enzymes of normolipemic rat. 1) Vitamin B2-butyrate (100 mg/kg) and nicomol (lg/Kg) increased carnitine acetyltransferase and D-amino acid oxidase activities, respectively, while these drugs had no influence on body weight, liver weight, serum and liver triglyceride, and serum and liver cholesterol levels. 2) ML-236B (300 mg/kg) had no influence on biochemical values and on activities of peroxisomal enzymes containing catalase. 3) KF 1492 (300 mg/kg) had no influence on the biochemical values, but an increase in the activities of fatty acyl-CoA oxidizing system (FAOS) and carnitine acetyltransferase (CAT) participating hepatic lipid metabolism was observed. 4) Pantethine (lg/kg) had no influence on the biochemical values, except a little decrease in the growth rate. However, increase by about 10% in the activities of urate oxidase and D-amino acid oxidase was observed. Catalase activity was decreased to 60% of control level. From these results, it is concluded that, in contrast to clofibrate, vitamin B2-butyrate, nicomol, ML-236B, KF 1492 and pantethine have little influence on the lipid metabolism of normolipemic animal and on the hepatic peroxisomal enzymes, indicating that the action mechanism of these drugs may be different from that of clofibrate and that the participation of hepatic peroxisomes in hypolipidemic activities of these drugs may be little if any.

Animals↗

PubMed1996

Identification of a peroxisome proliferator-responsive element upstream of the human peroxisomal fatty acyl coenzyme A oxidase gene.

Peroxisome proliferators cause a rapid and coordinated transcriptional activation of genes encoding the enzymes of the peroxisomal beta-oxidation pathway in rats and mice. Cis-acting peroxisome proliferator responsive elements (PPREs) have been identified in the 5'-flanking region of H202-producing rat acyl-CoA oxidase (ACOX) gene and in other genes inducible by peroxisome proliferators. To gain more insight into the purported nonresponsiveness of human liver cells to peroxisome volume density and in the activity of the beta-oxidation enzyme system, we have previously cloned the human ACOX gene, the first and rate-limiting enzyme of the peroxisomal beta-oxidation system. We now present information on a regulatory element for the peroxidase proliferator-activated receptor (PPAR)/retinoid X receptor (RXR) heterodimers. The PPRE, consists of AGGTCA C TGGTCA, which is a direct repeat of hexamer half-sites interspaced by a single nucleotide (DR1 motif). It is located at -1918 to -1906 base pairs upstream of the transcription initiation site of this human ACOX gene. This PPRE specifically binds to baculovirus-expressed recombinant rat PPAR alpha/RXR alpha heterodimers. In transient transfection experiments, the maximum induction of luciferase expression by ciprofibrate and/or 9-cis-retinoic acid is dependent upon cotransfection of expression plasmids for PPAR alpha and RXR alpha. The functionally of this human ACOX promoter was further demonstrated by linking it to a beta-galactosidase reporter gene or to a rat urate oxidase cDNA and establishing stably transfected African green monkey kidney (CV1) cell lines expressing reporter protein. The human ACOX promoter has been found to be responsive to peroxisome proliferators in CV1 cells stably expressing PPAR alpha, whereas only a basal level of promoter activity is detected in stably transfected cells lacking PPAR alpha. The presence of a PPRE in the promoter of this human peroxisomal ACOX gene and its responsiveness to peroxisome proliferators suggests that factors other than the PPRE in the 5'-flanking sequence of the human ACOX gene may account for differences, if any, in the pleiotropic responses of humans to peroxisome proliferators.

Acyl-CoA Oxidase↗

PubMed1985

Tiadenol-mediated induction of peroxisomal enzymes in cultured C3H/10T1/2CL8 cells and in chemically transformed C3H/10T1/2 MCA16 cells.

The levels of peroxisomal enzyme activities in cultured C3H/10T1/2 CL8 cells and in chemically transformed C3H/10T1/2 MCA16 cells were studied after treatment with tiadenol and niadenate, two hypolipidemic drugs which are both carcinogenic and cause peroxisome proliferation in vivo. Administration of these peroxisome proliferators to the cells resulted in large increases in specific palmitoyl-CoA hydrolase, carnitine acetyl-transferase, and catalase activities. A reproducible induction of cyanide-insensitive palmitoyl-CoA oxidative activity was observed 5 and 9 days after initiation of tiadenol treatment. Basal activity was 0.16 nmole/min/mg protein compared to 0.95 nmole/min/mg protein in cells treated with 18 microM tiadenol (cytotoxicity of about 25%) for 9 days. The enzyme activities were more increased in the transformed MCA 16 cells than in the non-transformed cells and the order of increase in enzyme activities was: niadenate greater than tiadenol. In non-transformed cells, the specific activity of palmitoyl-CoA hydrolase was enhanced approximately 2.1-fold within 4 days after tiadenol treatment. During this time period the enzyme activity was constant in untreated cells, but decreased during longer incubation periods. The enhancement of palmitoyl-CoA hydrolase, carnitine acetyl-transferase and catalase activities was dose-related over a concentration range of 2 to 20 microM tiadenol, depending on the enzyme assayed. Tiadenol concentrations above 10 microM were increasingly cytotoxic, while 18 microM niadenate had no toxic effect on the C3H/10T1/2 C18 cells. Moreover, the stimulation of the 3 enzyme activities by the peroxisome proliferators were inhibited by cycloheximide. Neither of the two cell lines contained any appreciable urate oxidase activity. The responses of these cells to hypolipidemic drugs show that they constitute a useful system for studies on the role of peroxisomes in lipid metabolism and the relationship between hypolipidemic activity and carcinogenic potential of these drugs.

Animals↗

PubMed2004

Outcome of children with B cell lymphoma in Venezuela with the LMB-89 protocol.

BACKGROUND: We analyzed the results of the LMB-89 protocol performed in seven centers in Venezuela in 96 children having B-cell non-Hodgkin lymphoma treated from 1995 to 2002. PROCEDURE: Mean age was 7.1 years with 71 (74%) been male. Eighty-two patients (85%) had diffuse small cell lymphoma Burkitt and Burkitt-like, and 14 (15%) had diffuse large B-cell lymphoma. Initial disease sites included the abdomen in 67%, peripheral nodes in 8%, and mediastinal in 4%. Treatment was directed to risk groups as described for LMB-89 protocol. Group A: seven patients (7%), group B: 80 patients (83%), and group C: nine patients (9%). RESULTS: Mean follow-up was 35 +/- 31 months. Complete remission (CR) occurred in 70 patients (73%); four patients (6%) had relapse during the first year and ten patients (10%) had progressive disease. Overall survival (OS) and event free survival (EFS) were 85 and 80% at 1 year, and 82 and 75% at 2 years, respectively. The EFS by therapeutic groups at 3 years was A: 100%; B: 76%, and C: 56%. TOXICITY: neutropenia in 75%, thrombocytopenia in 63%, febrile neutropenia in 39%. Viral infections: hepatitis B in 20%, hepatitis C in 2%, and Herpes zoster in 3%. Tumor lysis syndrome (TLS) occurred in 9% during induction phase with a high mortality of 44% (urate-oxidase was available only at the end of the study). CONCLUSIONS: The high mortality rate during induction phase prohibited a better EFS. Prophylactic use of xantine-oxidase may improve future results. The high incidence of hepatitis B requires a vaccination program.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1996

Iodixanol (Optiprep), an improved density gradient medium for the iso-osmotic isolation of rat liver peroxisomes.

The suitability of Iodixanol {5,5'-[(2-hydroxy-1, 3-propanediyl)-bis(acetylamino)] bis-[N,N'-bis(2, 3-dihydroxypreopyl-2,4,6-triiodo-1,3-benzenecarboxamide)]}, a nonionic iodinated compound with a molecular weight of 1550, for the isolation of peroxisomes from rat liver was investigated. Centrifugation of light mitochondrial fractions in 20 to 40% (w/v) Iodixanol gradients, made iso-osmotic by the addition of sucrose, resulted in an excellent separation of peroxisomes from the remaining organelles, which were not able to enter the gradient. Peroxisomes banded around 30% (w/v) Iodixanol (d approximately 1.175) and, as revealed by marker enzyme analysis, were enriched 35- to 40-fold. Morphological examination of the peroxisomal fractions confirmed the near absence of other organelles and revealed structurally well-preserved peroxisomes. Free cores, also present in the starting fractions, migrated to higher densities and were trapped on a cushion. No interference of Iodixanol with marker enzyme determinations was observed, except for the UV-metric determination of urate oxidase and for the analysis of protein.

Animals↗

PubMed2000

A missense mutation in the RING finger motif of PEX2 protein disturbs the import of peroxisome targeting signal 1 (PTS1)-containing protein but not the PTS2-containing protein.

SK24 and PT54 mutant cells, which are peroxisome-deficient Chinese hamster ovary (CHO) cells isolated using peroxisomal forms of green fluorescent protein (GFP), were found to be defective in the PEX2 gene. The nucleotide sequences of PEX2 cDNA from the mutant cells were determined to identify mutation sites in the mutant cells. The mutation in SK24 cells changed cysteine to tyrosine at amino acid position 258, which is a component of the RING finger (C(3)HC(4)) motif in the carboxyl terminus of the protein. PT54 cells contained a nonsense mutation in the codon for glutamine at position 101, resulting in premature termination. The immunocytochemical analyses revealed distinct phenotypes between mutant cells defective in the PEX2 gene. Both mutant cells exhibited cytosolic mislocalizations on catalase and urate oxidase containing PTS1. On the other hand, on 3-ketoacyl-CoA thiolase containing PTS2, PT54 cells exhibited cytosolic mislocalization, but SK24 cells exhibited peroxisomal localization. When wild-type or mutant-type PEX2 cDNA was transfected into both mutant cells, the stable transformants restored the phenotype in accordance with the transfected cDNA. These observations indicate that an amino acid substitution, cysteine-258 to tyrosine, in the RING finger motif of PEX2 protein, whose function is required for peroxisomal localizations of both PTS1- and PTS2-containing proteins, results in a complete defect in the PTS1 pathway but not in the PTS2 pathway.

Amino Acid Sequence↗

PubMed2001

Temperature-sensitive phenotype of Chinese hamster ovary cells defective in PEX5 gene.

SK32 mutant cells, which were isolated as peroxisome-deficient Chinese hamster ovary (CHO) cells by an advantage of a visible peroxisome form of green fluorescent protein (GFP), were found to suffer from a functional loss of PEX5 gene encoding for PTS1R. The sequence analysis of cDNA indicated that PEX5 gene encoded for the two isoforms composed of 603 amino acids (PTS1RS) and 640 amino acids (PTS1RL). The mutation changed glycine to arginine at amino acid position 343 of PTS1RL (corresponding to the position 306 of PTS1RS) in SK32 cells. The mutant cells exhibited a temperature-sensitive (TS) phenotype on the peroxisomal localizations of the recombinant GFP and urate oxidase appending a genuine peroxisome targeting signal 1 (PTS1), a tripeptide of Ser-Lys-Leu (SKL) at the C-terminus, but did not on that of catalase harboring a divergent PTS1, Lys-Ala-Asn-Leu (KANL) sequence. 3-ketoacyl-CoA thiolase (hereafter referred to as thiolase), which harbors an extension sequence (PTS2) at the N-terminus, never appeared to be affected on the peroxisomal localization in the mutant cells. When thiolase was examined on the molecular size in the mutant cells, the enzyme existed as the larger precursor form in the peroxisomes at 37 degrees C and a considerable part (almost half) was converted to the mature size at 30 degrees C. These results indicate that the amino acid substitution, Gly306Arg in PTS1RS and/or Gly343Arg in PTSRL, gives rise to TS phenotype on the peroxisomal translocation of PTS1 proteins and the maturation of PTS2 protein.

Amino Acid Sequence↗

PubMed1984

Trichosporon adeninovorans sp. nov., a yeast species utilizing adenine, xanthine, uric acid, putrescine and primary n-alkylamines as the sole source of carbon, nitrogen and energy.

A new yeast species, Trichosporon adeninovorans, was isolated from soil by the enrichment culture method. Apart from adenine, the strain utilized uric acid, guanine, xanthine, hypoxanthine, 6,8-dihydroxypurine, putrescine, propylamine, butylamine, pentylamine, hexylamine and octylamine as sole source of carbon, nitrogen and energy. The structure of the cell wall of Tr. adeninovorans was ascomycetous. On the subcellular level growth on adenine or uric acid was accompanied with the development of microbodies in the cell. These cell organelles probably were the site of urate oxidase, an enzyme that, after growth on purine substrates, together with allantoinase was present at high activities. Low activities of adenine amidohydrolase and xanthine dehydrogenase were also demonstrated.

Adenine↗

PubMed1991

Pancreatic hepatocytes. An in vivo model for cell lineage in pancreas of adult rat.

Multiple foci of hepatocytes differentiate in the pancreas of adult rats subjected to a copper depletion-repletion regimen. Copper deficiency for seven to nine weeks causes an irreversible depletion of over 80% of the acinar cells in the pancreas. When transferred to a normal diet, these rats exhibit only a minimal and spotty acinar cell recovery. This disruption of tissue organization appears to trigger a profound change in cellular commitment, which leads to hepatocyte differentiation in the "oval cells" in the periductal interstitium and the epithelial cells lining the small pancreatic ductules. Pancreatic hepatocytes express several liver-specific genes including albumin, a2u-globulin, carbamoylphosphate synthetase-I, and urate oxidase. Both carbamoylphosphate synthetase-I and glutamine synthetase, the ammonia-metabolizing enzymes, are expressed by all pancreatic hepatocytes; in liver, these are expressed by different populations of hepatocytes. The magnitude of hepatocyte differentiation in this model should facilitate studies on the molecular events regulating changes in cell lineage or differentiation commitment within the pancreas.

Animals↗

PubMed1987

Localization of pipecolic acid metabolism in rat liver peroxisomes: probable explanation for hyperpipecolataemia in Zellweger syndrome.

The metabolism of [14C]pipecolic acid was studied in peroxisomal fractions of rat liver obtained by density gradient centrifugation in Percoll. The production rate of [14CO2] was used to measure the metabolic activity of the fractions towards [14C]carboxypipecolic acid as a substrate. It was shown that this activity was located in the peroxisomal fractions by comparison with the peroxisomal marker enzyme urate oxidase (EC 1.7.3.3). The process was markedly elevated by the addition of FAD. The apparent Km for DL-pipecolic acid was found to be 1.2 mmol L-1. Addition of ATP (1 mmol L-1) did not influence the decarboxylation rate of pipecolic acid. These results might explain the defective metabolism of pipecolic acid in patients with Zellweger syndrome who are lacking peroxisomes.

Animals↗

PubMed1996

Mutational analysis of the C-terminal region of AREA, the transcription factor mediating nitrogen metabolite repression in Aspergillus nidulans.

In Aspergillus nidulans the positive-acting, wide domain regulatory gene areA mediates nitrogen metabolite repression. Previous analysis demonstrated that the C-terminal 153 residues of the areA product (AREA) are inessential for at least partial expression of most genes subject to regulation by areA. Paradoxically, areAr2, a -1 frameshift replacing the wild-type 122 C-terminal residues with a mutant peptide of 117 amino acids, leads to general loss of function. To determine the basis for the areAr2 mutant phenotype, and as a means of delineating functional domains within the C-terminal region of AREA, we have selected and characterised areAr2 revertants. Deletion analysis, utilising direct gene replacement, extended this analysis. A mutant areA product truncated immediately after the last residue of the highly conserved GATA (DNA-binding) domain retains partial function. The areAr2 product retains some function with respect to the expression of uaZ (encoding urate oxidase) and the mutant allele is partially dominant with respect to nitrate reductase levels. Consistent with the areAr2 product having a debilitating biological activity, we have demonstrated that a polypeptide containing both the wild-type DNA-binding domain and the mutant C-terminus of AREA2 is able to bind DNA in vitro but no longer shows specificity for GATA sequences.

Amino Acid Sequence↗

PubMed1996

Contributions of the immunogold technique to investigation of the biology of peroxisomes.

The immunogold labeling technique has been extremely useful in investigation of the structure and function of peroxisomes. In this report a few examples of the application of this technique with significant implications in the field are briefly reviewed. The problem of extra-peroxisomal catalase, the subject of long controversy between the biochemists and cytochemists, was settled with the immunogold technique, which unequivocally revealed the presence of that enzyme not only in the cytoplasm, but also in the euchromatin region of nucleus, in addition to peroxisomes. On the other hand, lactate dehydrogenase, a typical cytoplasmic protein, has also been shown recently to be present in peroxisomes and to be involved in the reoxidation of NADH produced by the peroxisomal beta-oxidation system. The immunogold technique has revealed several distinct compartments in the matrix of mammalian peroxisomes: urate oxidase in the crystalline cores, alpha-hydroxy acid oxidase B in the marginal plates and D-amino acid oxidase in a non-crystalline condensed region of matrix. The specific alterations of peroxisomal proteins are reflected in their immunolabeling density with gold particles. Quantitation of gold-label by automatic image analysis has revealed that the induction of lipid beta-oxidation enzyme proteins by diverse hypolipidemic drugs is initiated and more pronounced in the pericentral regions of the liver lobule. Finally, immunogold labeling with an antibody to 70 kDa peroxisomal membrane protein has identified a novel class of small peroxisomes that initially incorporate radioactive amino acids more efficiently than regular peroxisomes and thus may represent early stages in the biogenesis of peroxisomes.

Animals↗

PubMed1999

Species differences in induction of hepatic enzymes by BM 17.0744, an activator of peroxisome proliferator-activated receptor alpha (PPARalpha).

BM 17.0744, a new anti-diabetic and lipid-lowering agent, leads also to strong hepatomegaly and carnitine acetyl transferase (CAT) increase in the liver of rats, a phenomenon known from fibrates. For information on the relevance of changes in liver of rats to other species, we investigated the effects of BM 17.0744 on lipids and selected marker enzymes related to beta-oxidation in rats, dogs and guinea-pigs, so-called high and low responders to peroxisome proliferators. To examine selectivity other enzymes were also determined, e.g. esterase, urate oxidase (UOX) and cytochrome c oxidase (CYT.C.OX.). Lowering of triglycerides and cholesterol in blood serum and/or liver was observed in pharmacological dose range in the three species tested. In dogs and guinea-pigs, liver and kidney weights were unaffected even in dogs in medium and high dose groups with high systemic exposure and severe toxicity. In male Sprague-Dawley rats treatment with 1.5, 3, 6 and 12.5 mg/kg per day BM 17.0744 selectively elevated the activities of CAT and acyl-CoA oxidase (AOX) by < or =200 and 20-fold, respectively. Administration of BM 17.0744 to Beagle dogs (1.5, 4, 12 mg/kg per day) and guinea-pigs (3 and 12 mg/kg per day) enhanced the activities of CAT and AOX dose-dependently by a factor of two to three only. Immunoblotting revealed a drug-specific enhancement of the amount of beta-oxidation enzymes in rats, which is in accord with the rapid and coordinated transcriptional activation shown in Northern dot blot analysis. Nuclear run-on assays demonstrated a real transcriptional activation. BM 17.0744 activates peroxisome proliferator-activated receptor alpha (PPARalpha), which could be shown by transactivation assays. The stimulation of PPARalpha by BM 17.0744 was stronger than that of the known ligands WY 14.643 and ETYA. Activation of PPARgamma can be excluded. Taken collectively, the data demonstrate an enhancement of the beta-oxidation system by BM 17.0744 paralleled by lipid-lowering in all species investigated. The activation of the nuclear factor PPARalpha may explain the changes in liver and the metabolic effects on the molecular level. The lack of an increase in liver and kidney weights and the relatively moderate enhancement of activities of beta-oxidation-related enzymes in dogs and guinea-pigs indicate that the excessive response observed in rats is not applicable to other, predominantly non-rodent, species. On the basis of these data and the experience with fibrates a specific risk for humans is not expected.

Animals↗

PubMed2003

Acute tumor lysis syndrome in solid tumors--a case report and review of the literature.

PURPOSE: Tumor lysis syndrome (TLS) is a potential complication in cancer therapy. It may occur in highly sensitive tumors, especially in childhood cancers and acute leukemias, whereas it is rare in the treatment of adult solid tumors. TLS is characterized by hyperuricemia, hyperkalemia, hyperphosphatemia and hypocalcemia following massive lysis of malignant cells. Complications include acute renal failure and metabolic acidosis. We report the first case of TLS during chemotherapy in a patient with metastatic medulloblastoma, together with a review of the literature regarding the occurrence of TLS in patients with solid tumors. METHODS: Data regarding clinical and biochemical parameters were extracted from the actual patients' files. Reports of TLS in the English language literature up to 2002 were identified by searching Medline. RESULTS: A 23-year old male with metastatic medulloblastoma received chemotherapy with cisplatin and etoposide due to massive extracerebral manifestations including metastases to the liver, mediastinal lymph nodes and bone marrow metastases. The patient developed classical signs of TLS on the second day of chemotherapy, including acute renal failure. A 17-fold increase in plasma LDH up to 87608 U/l was observed together with a 4-fold increase in plasma creatinine. The patient was treated with aggressive hydration, allopurinol and repeated hemodialysis. During the following days the patient improved and the biochemical markers all returned to normal. REVIEW. Reviewing the literature, a total of 45 patients with solid tumors who developed TLS have been reported. Most of the patients presented with metastatic, therapy-sensitive disease. Although preventable in practically 100% of patients, TLS is a potentially fatal complication, and in this material the mortality rate was one in three. Risk factors included increased LDH, hyperuricemia and pretreatment azotemia. CONCLUSIONS: TLS is only rarely associated with treatment of solid tumors. Precautions should be taken to avoid this potentially fatal complication in (chemo)therapy of solid tumors, especially in therapy-sensitive tumors presenting with bulky, metastatic disease and preexisting risk factors, including azotemia, elevated LDH and hyperuricemia. Prophylactic treatment to avoid TLS includes allopurinol, hydration prior to treatment and alkalization of the urine. Urate oxidase (rasburicase) is now beginning to replace allopurinol as a more effective way of reducing hyperuricemia and thereby the risk of TLS.

Adult↗

PubMed2006

The relationship between uric acid and its oxidative product allantoin: a potential indicator for the evaluation of oxidative stress in birds.

Uric acid is the main nitrogenous waste product in birds but it is also known to be a potent antioxidant. Hominoid primates and birds lack the enzyme urate oxidase, which oxidizes uric acid to allantoin. Consequently, the presence of allantoin in their plasma results from non-enzymatic oxidation. In humans, the allantoin to uric acid ratio in plasma increases during oxidative stress, thus this ratio has been suggested to be an in vivo marker for oxidative stress in humans. We measured the concentrations of uric acid and allantoin in the plasma and ureteral urine of white-crowned sparrows (Zonotrichia leucophrys gambelii) at rest, immediately after 30 min of exercise in a hop/hover wheel, and after 1 h of recovery. The plasma allantoin concentration and the allantoin to uric acid ratio did not increase during exercise but we found a positive relationship between the concentrations of uric acid and allantoin in the plasma and in the ureteral urine in the three activity phases. In the plasma, the slope of the regression describing the above positive relationships was significantly higher immediately after activity. We suggest that the slope indicates the rate of uric acid oxidation and that during activity this rate increases as a result of higher production of free radicals. The present study demonstrates that allantoin is present in the plasma and in the ureteral urine of white-crowned sparrows and therefore might be useful as an indicator of oxidative stress in birds.

Allantoin↗

PubMed2005

[Tumor lysis syndrome: risk factors and treatment].

Tumor lysis syndrome is a typical oncological complication, characterized by hyperuricemia, hyperkalemia, hyperphosphatemia with secondary hypocalcemia, acidosis and acute renal failure. it occurs particularly in patients with lymphoproliferative diseases during therapy with potent myelosuppressive substances. patients with solid tumors rarely develop a tumor lysis syndrome during anti-neoplastic therapy (chemo-, hormonal-, steroid therapy, radiotherapy). host-related (e.g. pre-existing volume depletion, hyperuricemia, acidic urine) and tumor-related (e.g. large tumor burden, tumor sensitivity to therapy, advanced stage) risk factors contribute markedly to the development of tumor lysis syndrome. prophylaxis and treatment of tumor lysis syndrome consist of adequate hydration of the patients (3 l fluid/m2/day) in order to maintain urine production of > or =100 ml/h, controlled alkalinisation (urine pH 7.0-7.5) and, if necessary, extracorporeal therapy (intermittent or continuous hemodialysis or hemodiafiltration). recombinant urate oxidase (rasburicase) reduces uric acid values by far more effectively than allopurinol. treatment with rasburicase (01.-0.2 mg/kg for 1-7 days) does not only markedly reduce the incidence of tumor lysis syndrome in patients with malignancy but also morbidity and mortality. hyperphosphate-induced acute renal failure due to intrarenal calcium phosphate precipitation may, however, occur even during rasburicase therapy

Clinical Trials as Topic↗

PubMed2001

Difficult gout and new approaches for control of hyperuricemia in the allopurinol-allergic patient.

A major obstacle to the treatment of hyperuricemia in patients allergic to allopurinol is the limited availability of suitable, equally effective, alternative, urate-lowering drugs. Conventional uricosuric drugs, including probenecid and sulfinpyrazone, are recommended for allopurinol- intolerant patients with gout and "underexcretion" hyperuricemia who have normal renal function and no history of nephrolithiasis. Therapeutic options in those in whom traditional uricosuric drugs are contraindicated, ineffective, or poorly tolerated include slow oral desensitization to allopurinol and cautious administration of oxipurinol. Allopurinol desensitization is useful particularly in those who have failed other treatment modalities. If available (as in Europe, South Africa, and Japan), benzbromarone may be tried in patients with gout and mild-to-moderate renal insufficiency. Recombinant urate oxidase can be used in the short-term prophylaxis and treatment of chemotherapy- associated hyperuricemia in patients with lymphoproliferative and myeloproliferative disorders. Hyperuricemia and gout occur with increased frequency in cyclosporine-treated allograft transplant recipients. The management of gout in these patients is complicated by two main factors: cyclosporine-induced renal impairment, and interactions with medications used to preserve the allograft.

Allopurinol↗

PubMed1983

Peroxisomal and mitochondrial palmitoyl coenzyme A beta-oxidation activities in rat white adipose tissue and their regulation in hypothyroidism.

A peroxisomal fraction with catalase and CN- -insensitive palmitoyl CoA beta-oxidative activity different from the CN- -sensitive mitochondrial palmitoyl CoA beta-oxidative activity was purified from rat epididymal and perirenal white adipose tissue by differential and sucrose density gradient centrifugations. The degree of purification of this fraction as compared to the nuclei-free and fat-free homogenate was 10 and 34 for catalase and palmitoyl CoA beta-oxidative activity, respectively. The finding that it was devoid of urate oxidase activity suggests that white adipose tissue peroxisomes are anucleoid. The contributions of the peroxisomes and of the mitochondria to total beta-oxidative activity in white adipose tissue were 65 and 35%, respectively. Hypothyroidism induced a 2.0- and 2.4-fold decrease of mitochondrial and peroxisomal beta-oxidation specific activities, respectively. These results are discussed in terms of a possible thermogenic role for white adipose tissue peroxisomes.

Adipose Tissue↗