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Z Zídek

Publications and source records attributed to Z Zídek.

50 records · Page 3Linked to original sources
PubMed1981

Increased acetylation and elimination of sulphadimidine in rats with adjuvant induced arthritis.

Control rats and rats with adjuvant-induced arthritis (AA) were given sulphadimidine (40 mg/kg body weight, i.v.). The absolute amount of total sulphadimidine (unchanged + acetylated) eliminated in urine was similar in both sexes of control rats, females, having, however, a higher proportion of acetylsulphadimidine (Ac-S) than males (on average 64% and 46%, respectively). Marked promotion of elimination of sulphadimidine to urine was found after adjuvant treatment in both sexes (by 52% in females and 64% in males). The main component of this excess was Ac-S, representing 99.6% of the increased amount in males, and 74.1% in females. Due to the developing hypoalbuminemia, blood protein-bound sulphadimidine decreased from the control value of 74% to 60% in AA animals. This change had no immediate relation, however, to the elevated production and elimination of Ac-S. It is suggested that as contrary to the impairment of microsomal drug metabolism, mycobacterial adjuvant does not impair, but even stimulates the extra-microsomal metabolism, at least as far as the acetylation is concerned.

Acetylation↗
PubMed1976

Sex and genetic differences in the elimination of sulphadimidine in rats.

Rats of five inbred strains and two random-bred stocks were intravenously given sulphadimidine (40 mg/kg body weight). A relatively low percentage of acetylsulphadimidine (Ac-S) in urine and absence of strain differences were found in males, whereas two phenotypes can be distinguished in females: (1) high percentage of Ac-S in urine, and (2) low percentage of Ac-S in uirne. An autosomal control of these differences is suggested. A dominant allele which determines the high percentage of excreted Ac-S manifests itself only in female endo-environment.

Acetylation↗
PubMed1975

Adjuvant arthritis in Lewis and AVN inbred strain of rats.

The authors analysed the manifestations of adjuvant arthritis in inbred Lewis and AVN rats and in subsequent generations (F1, F2, B1, B2), using a subjective (scoring system) and an objective criterion (paw volume). The results obtained were in good correlation. Marked variability of the systemic symptoms of the disease was found not only in the parent generation but also in the subsequent generations.

Animals↗
PubMedDate not supplied

Immunomodulatory properties of antiviral acyclic nucleotide analogues: cytokine stimulatory and nitric oxide costimulatory effects.

Acyclic nucleotide analogues exhibit strong activity against a broad range of viruses, including HIV-1 and -2. We have investigated their effects on in vitro secretion of cytokines and production of nitric oxide (NO) by murine peritoneal macrophages, factors known to play a role in virus replication. Included in the study were the most prominent compounds of the series: 9-(2-phosphonomethoxyethyl)adenine, 9-(2-phosphonomethoxyethyl)-2,6-diaminopurine, the (R)- and (S)-enantiomers of 9-(2-phosphonomethoxypropyl) adenine [(R)- or (S)-PMPA], (R)- and (S)-enantiomers of 9-(2-phosphonomethoxypropyl)-2,6-diaminopurine [(R)- or (S)-PMPDAP], 9-(2-phosphonomethoxyethyl)guanine (PMEG), and (S)-enantiomer of 1-(3-hydroxy-2-phosphonomethoxypropyl)cytosine [(S)-HPMPC]. PMEG, (R)-PMPA, and (S)-PMPA greatly enhanced the secretion of both tumour necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10), (R)-PMPDAP stimulated only TNF-alpha, other test compounds were ineffective. None of them influenced the secretion of IL-2 or interferon-gamma (IFN-gamma). Both TNF-alpha and IL-10 have been found to be major factors determining enhancing effects of PMEG, (R)-PMPA, and (S)-PMPA on production of NO generated by exogenous IFN-gamma. The study points to a possible implication of immunomodulatory properties in the antiviral effects of some acyclic nucleotide analogues. In addition, our data support the view that endogenous IL-10 can stimulate certain macrophage functions.

Adjuvants, Immunologic↗
PubMedDate not supplied

Antiinflammatory effects of phosphonomethoxyethyl analogues of adenine in a model of adjuvant arthritis.

The 9-(2-phosphonomethoxyethyl)adenine (PMEA) and its more bioavailable bis(pivaloyloxymethyl) ester, (bis-POM-PMEA), applied s.c. at doses of 5-50 mg/kg, profoundly suppress symptoms of rat adjuvant arthritis, such as paw swelling, sple-nomegaly, fibroadhesive perisplenitis and systemic NO levels. The 9-(2-phosphonomethoxypropyl)adenine, PMPA and bis-POC-PMPA are ineffective. The antiarthritic effect does not depend on the influence of the drugs on macrophage NO production.

Adenine↗
PubMedDate not supplied

Stimulation of cytokine and nitric oxide production by acyclic nucleoside phosphonates.

Several antiviral acyclic nucleotide analogues activate expression of genes for cytokines, such as TNF-alpha, IL-10 in macrophages and IFN-gamma in splenocytes. This is an underlying mechanism for substantially enhanced production of nitric oxide generated by IFN-gamma. More lipophilic prodrugs, bis-POM-PMEA and bis-POC-PMPA, are cytocidal for macrophages and thus inhibit nitric oxide formation.

Animals↗
PubMedDate not supplied

Antitumor activity of novel purine acyclic nucleotide analogs PMEA and PMEDAP.

PMEDAP and/or PMEA treatment of SD rat lymphomas significantly prolonged the mean survival time of tumor-bearing animals. Dose-dependent genotoxicity of both PMEDAP and PMEA was not observed in in vitro tests on stabilized diploid MRC-5 cell line. The mitotic activity of MRC-5 cells was completely inhibited after 48 hours exposure in culture medium containing PMEDAP (10 micrograms/ml), or PMEA (25 micrograms/ml), respectively. Significant concentration dependent inhibition of cell proliferation caused by PMEDAP and/or PMEA was also observed in murine splenocytes. The analogs specifically inhibit proliferation of mitogen-activated T-lymphocytes. Modulation of subpopulations of peripheral blood cells under in vivo conditions was found in inbred SD animals. Intraperitoneal administration of PMEDAP to young healthy SD animals induced the decrease of the CD4+/CD8+ value from 1.3-1.6 to 0.72 while i.p. application of PMEA caused a decrease of the same ratio to 0.62.

Adenine↗