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Dermatologica 1975Notwithstanding the intense interest in systemic cytotoxic therapy in recent years, the great majority in psoriatics are likely to go on needing topical therapy with... (Review)
Review
Notwithstanding the intense interest in systemic cytotoxic therapy in recent years, the great majority in psoriatics are likely to go on needing topical therapy with tar, dithranol or corticosteroids, and a welcome trend is the spreading of interest in day care centres such as those in Paris (GRUPPER), Stockholm (THYRESSON), Stanford (FARBER) and San Francisco (CRAM) evolving from the out-patient regimes advocated by INGRAM in Leeds a generation ago.
Topics: Adrenal Cortex Hormones; Anthralin; Azathioprine; Azauridine; Fluorouracil; Humans; Hydroxyurea; Lomustine; Mechlorethamine; Methotrexate; Psoriasis; Tars; Tretinoin; Ultraviolet Therapy
PubMed: 1098945
DOI: 10.1159/000251415 -
Journal of Nutritional Science and... Oct 1983The effect of pyridoxine on 6-azauridine triacetate (6-AzUrd-TA) induced hyper beta-alaninemia was studied in New Zealand albino rabbits in three experiments. In each of...
The effect of pyridoxine on 6-azauridine triacetate (6-AzUrd-TA) induced hyper beta-alaninemia was studied in New Zealand albino rabbits in three experiments. In each of the three experiments the animals were administered by gavage: Group 1 (Control), drinking water; Group 2, 6-AzUrd-TA; and Group 3, 6-AzUrD-TA with pyridoxine. While no beta-alanine was found in the control group or in pretreatment samples of the 6-AZUrd-TA and 6-AzUrd-TA + pyridoxine treated animals, high concentrations of this amino acid (191.0 +/- 91.6, 220.2 +/- 116.3, 103.2 +/- 64.4 nmol/ml) were found on the fourth and seventh days of 6-AzUrd-TA treatment with daily doses of 1.0 g/kg and 0.5 g/kg B.W. respectively. The drug induced hyper beta-alaninemia was significantly (p less than or equal to 0.05) reduced in all three experiments by simultaneous pyridoxine administration in daily doses of 50 mg/kg B. W. These results indicate, that daily repeated oral administration of 6-AzUrd-TA causes elevation of serum beta-alanine, which can be partially prevented by oral administration of pyridoxine. They also indirectly support the hypothesis, that 6-AzUrd-TA induced hyper beta-alaninemia is at least partially caused by the inhibition of beta-alanine degrading enzymes, that use pyridoxal phosphate as a coenzyme. Direct measurement of the enzyme activity is planned in our future studies.
Topics: Alanine; Animals; Azauridine; Drug Interactions; Female; Male; Pyridoxine; Rabbits; beta-Alanine
PubMed: 6198500
DOI: 10.3177/jnsv.29.631 -
Archives of Dermatology Sep 1974
Review
Topics: Animals; Antineoplastic Agents; Azathioprine; Azauridine; Bleomycin; Chlorambucil; Cyclophosphamide; Cytarabine; Dactinomycin; Humans; Hydroxyurea; Immunosuppressive Agents; Mercaptopurine; Methotrexate; Procarbazine; Skin Diseases; Skin Neoplasms; Vinblastine; Vincristine
PubMed: 4141602
DOI: No ID Found -
The Journal of Clinical Investigation Jul 1964
Topics: Azauridine; Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Metabolism; Nucleosides; Pharmacology; Pyrimidines
PubMed: 14192530
DOI: 10.1172/JCI105025 -
Biochemistry Oct 19801-(5'-Phospho-beta-D-ribofuranosyl)barbituric acid, an analogue of orotidylic acid, binds to orotidine-5'-phosphate decarboxylase about 100000 times as strongly as does...
1-(5'-Phospho-beta-D-ribofuranosyl)barbituric acid, an analogue of orotidylic acid, binds to orotidine-5'-phosphate decarboxylase about 100000 times as strongly as does the substrate. The Ki at pH 6 is 9 X 10(-12) M and the half-time for dissociation at 4 degrees C is about 10 h. The binding of the barbiturate analogue to the enzyme is thus one of the strongest interactions between small molecules and proteins that have been measured. The possibility that the inhibitor is a transition-state analogue is discussed.
Topics: Carboxy-Lyases; Chromatography, Gel; Kinetics; Orotidine-5'-Phosphate Decarboxylase; Saccharomyces cerevisiae; Spectrophotometry, Ultraviolet; Uracil Nucleotides; Uridine Monophosphate
PubMed: 7006681
DOI: 10.1021/bi00563a010 -
The Journal of Infectious Diseases Jan 1976The antiviral agents cytosine arabinoside, adenine arabinoside, and 6-azauridine were shown to inhibit the replication of rabies virus in vitro but not the replication...
The antiviral agents cytosine arabinoside, adenine arabinoside, and 6-azauridine were shown to inhibit the replication of rabies virus in vitro but not the replication of Sindbis virus. These same drugs were not effective in reducing the mortality rate in mice challenged with street rabies virus.
Topics: Animals; Antiviral Agents; Azauridine; Cell Line; Cytarabine; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; In Vitro Techniques; Mice; Purine Nucleosides; Rabies; Rabies virus; Vidarabine
PubMed: 1245759
DOI: 10.1093/infdis/133.1.7 -
Biopolymers Aug 1979
Theoretical drug design: 6-azauridine-5'-phosphate--its X-ray crystal structure, potential energy maps, and mechanism of inhibition of orotidine-5'-phosphate decarboxylase.
Topics: Azauridine; Carboxy-Lyases; Models, Molecular; Molecular Conformation; Orotidine-5'-Phosphate Decarboxylase; Thermodynamics; Uracil Nucleotides; X-Ray Diffraction
PubMed: 497352
DOI: 10.1002/bip.1979.360180814 -
Journal of Cellular Physiology Jun 1982A novel synergistic effect of several purine derivatives such as adenine, adenosine, hypoxanthine, and guanine on the toxicity of nucleoside analogs pyrazofurin and...
A novel synergistic effect of several purine derivatives such as adenine, adenosine, hypoxanthine, and guanine on the toxicity of nucleoside analogs pyrazofurin and 6-azauridine towards cultured Chinese hamster ovary (CHO) cells has been observed. The presence of the above purine derivatives enhanced the toxicity of pyrazofurin and 6-azauridine, in a dose dependent manner. The growth inhibitory effects of these nucleoside analogs either alone or in combination with the purine derivatives were reversed by uridine and cytidine, providing evidence that the synergistic effect of the purine derivatives was exerted at the level of pyrimidine nucleotide biosynthesis. Studies with mutant cells lacking various purine phosphorylating enzymes show that phosphorylation of purine derivatives through reactions utilizing phosphoribosylpyrophosate (PRPP) is essential for observing the synergistic response. It is suggested that the above purine derivatives (including adenosine, via conversion to hypoxanthine) exert their synergistic effects by depleting the cellular pool of PRPP by two separate mechanisms (direct utilization and feedback inhibition of its synthesis), which as a result becomes rate limiting in the synthesis of orotidine monophosphate (OMP). The reduced levels of OMP, which is a competing substrate with pyrazofurin- and 6-azauridine-5'-monophosphates for binding to the target enzyme OMP decarboxylase, could then account for the inhibition of the enzyme at lower concentrations of these analogs.
Topics: Adenine; Adenosine; Amides; Animals; Antimetabolites, Antineoplastic; Azauridine; Cell Line; Cell Survival; Cricetinae; Cricetulus; Dose-Response Relationship, Drug; Drug Synergism; Female; Hypoxanthines; Ovary; Purines; Pyrazoles; Ribonucleosides; Ribose; Structure-Activity Relationship
PubMed: 6178748
DOI: 10.1002/jcp.1041110310 -
Acta Virologica Apr 1976Twenty-five metabolites (purines, pyrimidines, nucleosides and nucleosides) were tested for their simultaneous action with 6-azauridine (AzUrd) in inhibition of...
Twenty-five metabolites (purines, pyrimidines, nucleosides and nucleosides) were tested for their simultaneous action with 6-azauridine (AzUrd) in inhibition of Newcastle disease virus (NDV) replication. With the exception of deoxyadenosine and cyclic AMP all natural adenine derivatives exerted a synergic effect with AzUrd like ATP. Glutamine in combination with AzUrd did not inhibit NDV replication. The inhibitory effect of the combination of AzUrd and adenine derivatives was reversible by guanosine, uridine and cytidine but not by orotic acid or orotidylic acid.
Topics: Adenine; Azauridine; Culture Techniques; Drug Synergism; Newcastle disease virus; Orotic Acid; Purine Nucleosides; Purine Nucleotides; Pyrimidine Nucleosides; Pyrimidine Nucleotides; Virus Replication
PubMed: 5863
DOI: No ID Found -
Scientific Reports Jun 2021Reverse genetics is an important tool in the elucidation of viral replication and the development of countermeasures; however, these methods are impeded by laborious and...
Reverse genetics is an important tool in the elucidation of viral replication and the development of countermeasures; however, these methods are impeded by laborious and inefficient replicon delivery methods. This paper demonstrates the use of a baculovirus to facilitate the efficient delivery of autonomous CHIKV replicons into mosquito and mammalian cells in vitro as well as adult mosquitoes in vivo. The efficacy of this approach was verified via co-localization among an eGFP reporter, nsP1, and dsRNA as well as through the inhibition of an RNA-dependent RNA polymerase (RdRp) null mutation (DDAA) in nsP4, or the treatment of a known antiviral compound (6-azauridine). We also investigated the correlation between CHIKV replicon-launched eGFP expression and the effectiveness of CHIKV replicon variants in inducing IFN-β expression in human cell lines. This delivery method based on a single vector is applicable to mosquito and mammalian cells in seeking to decipher the mechanisms underlying CHIKV replication, elucidate virus-host interactions, and develop antivirals. This study presents an effective alternative to overcome many of the technological issues related to the study and utilization of autonomous arbovirus replicons.
Topics: Aedes; Animals; Antiviral Agents; Chikungunya Fever; Chikungunya virus; Chlorocebus aethiops; Culicidae; Humans; Mosquito Vectors; RNA, Viral; RNA-Dependent RNA Polymerase; Vero Cells; Viral Nonstructural Proteins; Virus Replication
PubMed: 34112897
DOI: 10.1038/s41598-021-91830-y