Synthesis, biological properties and anti-HIV-1 activity of new pyrimidine P1,P2-dinucleotides.

New homo- and hetero-P(1),P(2)-dinucleotides were prepared with the use of multistep procedures starting from the monophosphates of 3'-fluoro-2-thiothymidine, 3'-fluoro-4-thiothymidine, AZT and 1-[(2-hydroxyethoxy)-methyl-5-propyl-6-phenylselenenyl]uracil. Anti-HIV properties of the synthesized P(1),P(2)-dinucleotides were evaluated against laboratory syncytia inducing strain HIV-1 in CEM-T4 cells. Anti-HIV activities were in the range of 5-45 nM, and therapeutic indexes were higher than 4666-14000. Interactions of the above mentioned compounds with recombinant HIV-1 reverse transcriptase were also investigated. The obtained results point to reverse transcriptase inhibition, with somewhat lower inhibitory activity than that of their parental nucleoside-5'-triphosphates. Compound 6 may be regarded as a potent anti-HIV/AIDS drug.

[Uniform programme in caring for patients with acute hepatic porphyria]. / Ujednolicony program postepowania z chorymi na ostre porfirie watrobowe.

The programme commissioned by the Ministry of Health is presented. Data basis for the years 1996-1998 were created. A booklet on diagnosis, treatment and prophylaxis of porphyrias was edited and distributed in Poland in 5000 copies to all hospitals, major laboratories, medical libraries, regional officers as well as patients. The booklet lists simple diagnostic methods which can be easily introduced to hospital laboratories for early diagnosis of porphyria. It also includes a list of the safe drugs for patients with porphyria. Several lectures for doctors and medical staff were delivered, nine publications appeared and six others were accepted for publication. Results of the work, evaluated after three years are as follows. Early clinical diagnosis of porphyria and its prophylaxis among family members has significantly improved. The frequency of severe attacks and the mortality rate due to porphyria has been reduced to singular cases. The proposed organization of small regional centers (with help of Porphyria Center), oriented at early diagnosis of porphyria appears to be impossible without further financial support.

cDNA cloning of Physarum polycephalum DNA topoisomerase I and expression analysis in plasmodia treated with cAMP.

cDNA encoding DNA topoisomerase I from Physarum polycephalum was isolated from a poly(A)+ -primed library (3'-region) and by PCR (5'-region). The coding region of cDNA was 3045 bp, encoding a polypeptide of molecular mass of 112 kDa. Identity between predicted amino acids sequences of conserved domains and corresponding domains from another eukaryotic type I DNA topoisomerases varied from 33.2 to 53.5% for the core domain and from 33.8 to 57.4% for the C-terminal domain. A peculiar feature of Physarum DNA topoisomerase I was a stretch of repeated KPAX...X motifs in the N-terminal domain of the polypeptide. Although treatment of the plasmodia with db-cAMP increased relaxing activity of the DNA topoisomerase I several-fold, there was only a slight increase in the mRNA level.

[Initial evaluation of the diagnostic usefulness of tuberculin tests among the patients of the Center of Diagnosis and Treatment of AIDS]. / Wstepna ocena przydatnosci diagnostycznej próby tuberkulinowej w populacji pacjentów Centrum Diagnostyki i Terapii AIDS.

Tuberculin and Candida skin tests were done on 98 HIV(+) and 42 control HIV(-) patients of AIDS Diagnosis and Therapy Center in Warsaw. Prevalence of the positive Tuberculin tests in the control group was 29% and it was not significantly different from those groups of patients HIV(+) whose CD4 cell count was higher than 350. For those with CD4 cell count 350 or below, tests were positive only in two cases both of the patients with active tuberculosis. The prevalence of positive Candida tests was in the control group only 12% and such result did not differ significantly from any other group of HIV positive patients with different CD4 cell counts. It is concluded that routine Tuberculin skin tests might be of value due to low initial prevalence among patients of the AIDS Center and that those persons who undergo conversion into positive tests will be under high suspicion of TB asymptomatic infection. Low prevalence and rather random distribution of positive Candida skin tests shows their insufficiency as single reference tests in anergy panel.

[Initial assessment of the use of polymerase chain reaction (PCR) in diagnosis of tuberculosis among patients of the Center for Diagnosis and Treatment of AIDS]. / Wstepne badania zastosowania techniki reakcji lancuchowej polimerazy (PCR) w diagnostyce gruzlicy w populacji pacjentów Centrum Diagnostyki i Terapii AIDS.

This initial report on the use of PCR in diagnosis of TB was based on a group of 180 patients observed in the AIDS Diagnosis and Therapy Center in Warsaw. Out of 6 patients with positive results of PCR assay for MTB, five had positive AFB smears in induced sputum or BAL, two had positive MTB cultures. Five of them were treated with tuberculostatic drugs with clinical improvement and had negative sputum PCR MTB results after several weeks. Additional 11 patients with AFB positive sputum or BAL smears and negative PCR MTB were observed. None of them developed pulmonary tuberculosis, and none of them was confirmed by culture as MTB infection. The results presented in this paper confirm high specificity and sensitivity of polymerase chain reaction (PCR) as an fast diagnostic test very useful in the clinical settings of AIDS. With the increase of collected material further evaluation will be continued.