5-fluorouracil (5-FU) is an antimetabolite which prevents thymine synthesis and suppresses the utilization of preformed uracil. A variety of cutaneous reactions have been reported with the use of systemic 5-FU, the most common being photosensitivity. We report a case of 5-FU induced phototoxicity in a 73-year-old male. The patient had tender and slightly pruritic scaly and crusted erythema on sun-exposed areas. A biopsy revealed necrotic keratinocytes with epidermal degeneration. After the cessation of 5-FU, the skin lesions showed a marked improvement, and there was no further photosensitivity to the skin.
Aged ; Biopsy ; Dermatitis, Phototoxic* ; Erythema ; Fluorouracil ; Humans ; Keratinocytes ; Male ; Skin ; Thymine ; Uracil

The second-generation oral anticancer agent UFT is a combination of uracil, which has fluorouracil's (5-FU) degradation-inhibitory effect, and tegafur, which is slowly converted to 5-FU in vivo, and UFT shows a higher 5-FU concentration in the tumor tissues than is achieved by tegafur alone or with comparable doses of intravenous 5-FU. Mucocutaneous side reactions induced by UFT are rare and these include photosensitivity of the lichenoid and eczematous types, acral erythema, hyperpigmentation, palmoplantar keratoderma and scleroderma-like reactions, and discoid lupus erythematosus (DLE)-like eruption. However, there has been no report in the Korean medical literature on patients presenting with a DLE-like eruption associated with UFT. So, we report here a case of DLE-like eruption induced by oral UFT.
Erythema ; Fluorouracil ; Humans ; Hyperpigmentation ; Keratoderma, Palmoplantar ; Lupus Erythematosus, Discoid ; Tegafur ; Uracil

A mixture of tegafur and uracil (TEGASIL) is a common antineoplastic agent. Tegafur is a fluoropyrimidine structurally similar to 5-fluorouracil (5-FU); uracil slows the degradation of 5-FU by dihydropyrimidine dehydrogenase, which results in higher 5-FU concentrations in tumors. Mucocutaneous side effects induced by this agent are rare and include photosensitivity of lichenoid and eczematous types, acral erythema, hyperpigmentation and palmoplantar keratoderma. However, there have been no reports of fixed drug eruption associated with TEGASIL. We report here on a case of fixed drug eruption due to oral TEGASIL.
Dihydrouracil Dehydrogenase (NADP) ; Drug Eruptions ; Erythema ; Fluorouracil ; Hyperpigmentation ; Keratoderma, Palmoplantar ; Tegafur ; Uracil

PURPOSE: Tegafur, an oral prodrug of 5-fluorouracil (5-FU), has been used in the treatment of gastric cancers. UFT (tegafur + uracil) has been developed to enhance the efficacy of tegafur. This study was conducted to assess the pharmacokinetics (PK) of tegafur in gastric cancer patients given the ECU-E regimen (epirubicin, cisplatin, UFT-E, an enteric-coated formula of UFT). A preliminary evaluation of antitumor efficacy and toxicity of ECU-E regimen was also performed. MATERIALS AND METHODS: Of the 32 gastric cancer patients registered for the ECU-E regimen, 8 participated in the PK study. The plasma concentration of tegafur was determined using HPLC. RESULTS: Seven out of the 8 patients were evaluable for response after 2 cycles, and showed 3 partial responses, 1 stable disease and 3 progressive diseases. No major toxicities were observed. Plasma profiles of the tegafur after the first dose showed significant differences in the amount and rate of absorption, i.e., rapid absorption group vs. slow absorption group. The level of C(max) in the rapid absorption group was 1.8 fold higher, and the AUC(0-5h) 4 fold greater, than those in the slow absorption group, nonetheless, the steady state concentrations showed no significant difference. These data indicate that the different absorption rates may not affect the overall exposure to tegafur. The patients with low Cp(ss, peak) showed poor efficacy compared to those with high Cp(ss, peak), suggesting that the concentration of tegafur may be one of the pharmacodynamic determinants in patients administered with ECU-E. CONCLUSION: This study evaluated the pharmacokinetics of tegafur in gastric patients given the ECU-E regimen, and provides preliminary data on the relationship between the plasma tegafur level and the efficacy, which warrants further evaluation.
Absorption ; Chromatography, High Pressure Liquid ; Cisplatin* ; Epirubicin* ; Fluorouracil ; Humans ; Pharmacokinetics* ; Plasma ; Stomach Neoplasms* ; Tegafur* ; Uracil

Purine & pyrimidine nucleotides are basic constituents of cellular DNA and RNA polynucleotides. Their function includes regulation of cell metabolism and function, energy conservation and transport and formation of coenzymes and active intermediates of phospholipids and carbohydrate metabolism. The origin of cellular purines and pyrimidines is almost exclusively endogenous source, and the dietary purines play only a minor role. Diagnostic and clinical markers of purine and pyrimidine nucleotide disorders are the level of uric acid, xanthine, hypoxanthine, orotic acid, uracil, thymine, dihydrouracil, dihydrothymine, and succinyladenosine. Clinical manifestations of purine and pyrimidine metabolic disorders are crystalluria and acute renal failure, infections, failure to thrive, and anemia. One of purine metabolic disorders, Lesch-Nyhan disease, is X-linked recessive disorder, presenting motor delay, cerebral palsy, involuntary movements, self-injurious behavior, hyperurcemia, uricosuria, urinary calculi and gouty arthritis. Hypoxanthine-guanine phosphoribosyl transferase(HPRT) is deficient.
Acute Kidney Injury ; Anemia ; Arthritis, Gouty ; Carbohydrate Metabolism ; Cerebral Palsy ; Coenzymes ; DNA ; Dyskinesias ; Failure to Thrive ; Hypoxanthine ; Lesch-Nyhan Syndrome* ; Metabolism* ; Orotic Acid ; Phospholipids ; Polynucleotides ; Purines ; Pyrimidine Nucleotides ; Pyrimidines ; RNA ; Self-Injurious Behavior ; Thymine ; Uracil ; Uric Acid ; Urinary Calculi ; Xanthine ; Biomarkers

OBJECTIVETo establish a RP-HPLC method for simultaneous determination of thymine, hypoxanthine and uracil contents in medical pipefish.

METHODSamples were extracted with distilled water by ultrasonic wave and separated on Waters C18 column eluted with a mobile phase of 0.05 mol x L(-1) KFI2PO4-acetonitrile (97:3). The flow rate was 0.6 mL x min(-1). The determination wavelength was 260 nm and the column temperature was set at 40 degrees C.

RESULTThe method had good linearity in the range of 0.033-0.660 (r = 0.9996), 0.620-12.400 (r = 0.9999), 0.048-0.960 microg (r = 0.9995), with average recoveries of 98.67% (RSD 1.6%), 99.03% (RSD 0.74%), 98.65% (RSD 1.8%), for thymine, hypoxanthine and uracil respectively.

CONCLUSIONThe simultaneous determination method of thymine, hypoxanthine and uracil in medical pipefish is established by RP-HPLC for the first time. The contents of the three constituents in different kinds of medical pipefish are significantly different. The method is simple, rapid and sensitive, and can be used for control the quality of medical pipefish.

Animals ; Chromatography, High Pressure Liquid ; methods ; Hypoxanthine ; analysis ; Medicine, Chinese Traditional ; Smegmamorpha ; Thymine ; analysis ; Uracil ; analysis

BACKGROUND: UFT/oral leucovorin (LV) provided a safer, more convenient oral alternative to bolus i.v. 5-Fluorouracil/LV regimen for advanced colorectal cancer while producing equivalent survival. We evaluated the efficacy and safety of a combination of oxaliplatin and UFT/LV in patients with advanced colorectal cancer. METHODS: From January 1999 to December 2001, a total 28 patient with metastatic or relapsed colorectal cancer were enrolled in this study. Treatment was consisted of oxaliplatin 130 mg/m2 i.v. for 2 hours on day 1, and UFT 300 mg/m2 p.o. and LV 30 mg p.o. on day 1-21. Chemotherapy repeated every three weeks until disease progression. RESULTS: Of the 28 patients, 1 complete response and 10 partial responses were observed. The overall response rate was 39.3%. The estimated median time to progression and survival were 6.0 months and 18.2 months, respectively. Peripheral neuropathy was the most common adverse effect. But, peripheral neuropathy was mild (grade 1, 2) and reversible. From the 129 cycles analyzed, grade 3, 4 adverse effects were observed only 3% included neutropenia (1.5%), and thrombocytopenia (1.5%). There were no treatment-related deaths. CONCLUSION: This combination of oxaliplatin and UFT/oral leucovorin is active and feasible in patients with advanced colorectal cancer. The regimen deserve further evaluation in a phase III prospective study.
Colorectal Neoplasms* ; Disease Progression ; Drug Therapy ; Drug Therapy, Combination* ; Humans ; Leucovorin* ; Neutropenia ; Peripheral Nervous System Diseases ; Tegafur ; Thrombocytopenia ; Uracil

The study is to investigate the pharmacokinetics of S-1 capsule (tegafur, gimeracil and potassium oxonate capsule) in patients with advanced gastric cancer after single and multiple oral administration. Twelve patients with advanced gastric cancer were recruited to the study. The dose of S-1 for each patient was determined according to his/her body surface area (BSA). The dose for single administration was 60 mg every subject. The dose for multiple administration for one subject was as follows: 100 mg x d(-1) or 120 mg x d(-1), 28-days consecutive oral administration. The pharmacokinetic parameters of tegafur, 5-fluorouracil, gimeracil, potassium oxonate and uracil after single oral administration were as follows: (2,207 +/- 545), (220.0 +/- 68.2), (374.9 +/- 103.0), (110.5 +/- 100.8) and (831.1 +/- 199.9) ng x mL(-1) for Cmax; (11.8 +/- 3.8), (4.4 +/- 3.3), (7.8 +/- 5.1), (3.1 +/- 0.9) and (8.8 +/- 4.1) h for t1/2, respectively. After six days oral administration, the average steady state plasma concentrations (Cav) of tegafur, 5-fluorouracil, gimeracil, potassium oxonate and uracil were (2,425 +/- 1,172), (73.88 +/- 18.88), (162.6 +/- 70.8), (36.89 +/- 29.35) and (435.3 +/- 141.0) ng x mL(-1), respectively, and the degree of fluctuation (DF) were (1.0 +/- 0.2), (2.5 +/- 0.4), (3.1 +/- 0.8), (2.4 +/- 0.8) and (1.5 +/- 0.3), respectively. The cumulative urine excretion percentage of tegafur, 5-fluorouracil, gimeracil and potassium oxonate in urine within 48 h were (4.2 +/- 2.8) %, (4.7 +/- 1.6) %, (18.5 +/- 6.0) % and (1.7 +/- 1.2) %, repectively, after single oral administration of S-1. The results exhibited that tegafur had some drug accumulation observed, and gimeracil, potassium oxonate, 5-fluorouracil and uracil had no drug accumulation observed.
Administration, Oral ; Adult ; Aged ; Antimetabolites, Antineoplastic ; pharmacokinetics ; Capsules ; Drug Combinations ; Female ; Fluorouracil ; blood ; urine ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; Oxonic Acid ; blood ; pharmacokinetics ; urine ; Pyridines ; blood ; urine ; Stomach Neoplasms ; blood ; metabolism ; pathology ; urine ; Tegafur ; blood ; pharmacokinetics ; urine ; Uracil ; blood ; urine

We cultured the rabbit inner medullary collecting duct (IMCD) cells as monolayers on collagen-coated membrane filters, and investigated distribution of the P2Y receptors by analyzing nucleotide-induced short circuit current (Isc) responses. Exposure to different nucleotides of either the apical or basolateral surface of cell monolayers stimulated Isc. Dose-response relationship and cross-desensitization studies suggested that at least 3 distinct P2Y receptors are expressed asymmetrically on the apical and basolateral membranes. A P2Y2-like receptor, which responds to UTP and ATP, is expressed on both the apical and basolateral membranes. In addition, a uracil nucleotide receptor, which responds to UDP and UTP, but not ATP, is expressed predominantly on the apical membrane. In contrast, a P2Y1-like receptor, which responds to ADP and 2-methylthio-ATP, is expressed predominantly on the basolateral membrane. These nucleotides stimulated intracellular cAMP production with an asymmetrical profile, which was comparable to that in the stimulation of Isc. Our results suggest that the adenine and uracil nucleotides can interact with different P2Y nucleotide receptors that are expressed asymmetrically on the apical and basolateral membranes of the rabbit IMCD cells, and that both cAMP- and Ca2+-dependent signaling mechanisms underlie the stimulation of Isc.
Adenine ; Adenosine Diphosphate ; Adenosine Triphosphate ; Membranes ; Nucleotides ; Uracil ; Uracil Nucleotides ; Uridine Diphosphate ; Uridine Triphosphate

OBJECTIVETo study the chemical constitutes of Acantophora spicifera.

METHODCompounds were isolated by normal phase silica gel and Sephadex LH-20 gel column chromatography, and reverse-phase HPLC, as well as recrystallization. Their structures were elucidated by spectroscopic methods.

RESULTSeven compounds were isolated from A. spicifera and their structures were identified as aplysin (1), loloilide (2), (R)-(-)-dehydrovomifoliol (3), uracil (4), thymine (5), 1-methoxy-4-(1-propenyl) benzene (6).

CONCLUSIONThe compounds were obtained from this genus for the first time. Compound 6 was firstly obtained from marine organisms.

Chromatography ; methods ; Chromatography, High Pressure Liquid ; methods ; Rhodophyta ; chemistry ; isolation & purification ; Sesquiterpenes ; chemistry ; isolation & purification ; Styrenes ; chemistry ; isolation & purification ; Thymine ; chemistry ; isolation & purification ; Uracil ; chemistry ; isolation & purification