Nature and prevalence of risk factors associated to type B and C acute viral hepatitis cases in Bucharest, 1998-2000.

The main objective of the study was to calculate and report the prevalence of probable risk factors involved in the transmission of pathogenic agents among type B and C acute viral hepatitis cases confirmed in Bucharest (1998-2000). The standardized values of the risks detected in the 45-180 days preceding the onset of illness suggest that in both types of acute viral hepatitis considered in our study transmission associated to the individuals' behaviour (19.0%-hepatitis B and 20.1%-hepatitis C) seems more frequent than "iatrogenic" transmission; in case of hepatitis B, sexual contacts with more than one partner coming first (15.7%), whilst in case of hepatitis C the use of i.v. drugs (heroine) was most frequently incriminated (12.4%). The study reviews the present knowledge of the risk factors involved in the transmission of the disease and approaches prevention strategies.

DNA topoisomerases as targets for the anticancer drug TAS-103: DNA interactions and topoisomerase catalytic inhibition.

TAS-103 is a novel anticancer drug that kills cells by increasing levels of DNA cleavage mediated by topoisomerase II. While most drugs that stimulate topoisomerase II-mediated DNA scission (i.e., topoisomerase II poisons) also inhibit the catalytic activity of the enzyme, they typically do so only at concentrations above the clinical range. TAS-103 is unusual in that it reportedly inhibits the catalytic activity of both topoisomerase I and II and does so at physiologically relevant concentrations [Utsugi, T., et al. (1997) Jpn. J. Cancer Res. 88, 992-1002]. Without a topoisomerase activity to relieve accumulating torsional stress, the DNA tracking systems that promote the action of TAS-103 as a topoisomerase II poison would be undermined. Therefore, the effects of TAS-103 on the catalytic activity of topoisomerase I and II were characterized. DNA binding and unwinding assays indicate that the drug intercalates into DNA with an apparent dissociation constant of approximately 2.2 microM. Furthermore, DNA strand passage assays with mammalian topoisomerase I indicate that TAS-103 does not inhibit the catalytic activity of the type I enzyme. Rather, the previously reported inhibition of topoisomerase I-catalyzed DNA relaxation results from a drug-induced alteration in the apparent topology of the nucleic acid substrate. TAS-103 does inhibit the catalytic activity of human topoisomerase IIalpha, apparently by blocking the DNA religation reaction of the enzyme. The lack of inhibition of topoisomerase I catalytic activity by TAS-103 explains how the drug is able to function as a topoisomerase II poison in treated cells.

5,7-Disubstituted analogues of the mixed topoisomerase I/II poison N-[2-(dimethylamino)ethyl]acridine-4-carboxamide (DACA): DNA binding and patterns of cytotoxicity.

DACA is a DNA-intercalating agent and dual topoisomerase (topo) I/II inhibitor currently in clinical trial as an anticancer drug. Substitutions in the acridine ring of DACA have significant effects on biological activity, with 5-substituted analogues being more potent but relatively less active against cell lines that underexpress topo II, and the converse for 7-substituted analogues. A small series of 5,7-disubstituted analogues was therefore prepared and evaluated. The compounds were prepared by CDI-assisted coupling of the appropriate acridine acids. When these contained no or only one halogen atom, they could be prepared by Al/Hg amalgam reduction of the corresponding acridine acids. However, this method could not be used to prepare dihalogen-substituted acridine acids due to substantial dehalogenation, and these intermediates were synthesized via cyclization of the appropriate aldehydes to give the acridines directly. These compounds showed enhanced DNA binding compared with the parent DACA, indicating that the known favourable influence of 5-substituents on DNA binding is retained. Cell line studies showed that the 5,7-disubstituted compounds retained both the broad-spectrum effectiveness of the 7-monosubstituted analogues and the higher cytotoxic potency of the 5-monosubstituted analogues. The 7-chloro-5-methyl and 5-chloro-7-methyl analogues showed comparable in vivo antitumour activity to DACA in the subcutaneous colon 38 model, but were substantially more potent (optimal doses of 60 mg/kg compared with 200 mg/kg for DACA).

A clinical, epidemiological and laboratory study on avoiding the risk of transmitting viral hepatitis during vaccinations with the Dermojet protected by an anticontaminant disposable device.

Jet injectors may transmit blood-borne infections, such as hepatitis B virus (HBV) and human immunodeficiency virus (HIV). To evaluate the safety of an anticontaminant disposable device which protects the jet injector apparatus, 22,714 healthy subjects were intradermally inoculated (38,162 inoculations) with a variety of vaccines. All the subjects were systematically followed-up clinically and epidemiologically for 6-18 months after inoculation; blood samples from 1619 subjects, before and 60-75 days after inoculation, were examined by enzyme-linked immunosorbent assay (ELISA) for HBV, hepatitis C virus (HCV) and HIV. Before vaccination 212 (13.09%) subjects were positive: 204 positive for HBV markers and eight for the HCV marker. None of the subjects were positive for the anti-HIV marker. During the clinico-epidemiological surveillance and the laboratory investigations mentioned above no clinical viral hepatitis B or C case and no seroconversion to positivity for HBV or HCV markers among the susceptible persons in the group were reported. Considering that in similar situations there is a theoretical risk of transmission as high as 1 per 388 to 1 per 3367 injections and that in our case 38,162 inoculations were performed in 22,714 subjects with the same Dermojet protected by the same type of anticontaminant disposable device, no contamination risk being reported, the conclusion can be reached that jet injectors can be safely used in the medical practice if they are protected by the sterile anticontaminant disposable device.

[The epidemiological characteristics of influenza in a large urban center (B.) of Romania in 1991]. / Caractéristiques épidémiologiques de la grippe dans un grand centre urbain (B.) de Roumanie, en 1991.

The peculiarities of the 1991 influenza epidemics in a big urban centre (B.) of Romania were evaluated through clinical and epidemiological active survey and laboratory assays. The results revealed the low rate of endemic morbidity and its significant risk during the fourth trimester as compared to the first, the important implication of the infant population in maintaining the endemic morbidity and of the less than one year old children in the seasonal peaks of the first and fourth trimesters. The laboratory assays revealed the simultaneous circulation but with variable intensity of type A(H3N2), A(H1N1) and B influenza viruses, inducing a high humoral specific protection level in the population. So the risk is low of an important epidemics during 1992. The opportunity is discussed of the prophylactic vaccination with type A(H3N2), A(H1N1) and B circulating strains of all high risk groups, especially of the preschool children from collectivities.

[The evolutionary characteristics of an influenza epidemic in a large urban center (B.) of Romania between 1988 and 1990]. / Caractéristiques de l'évolution de l'épidémie de grippe dans un grand centre urbain (B.) de Roumanie dans l'intervalle 1988 à 1990.

The report presents the peculiar characteristics of influenza epidemics in a big urban centre (B.) of Romania, between 1988 and 1990, surveyed by clinical, epidemiological and laboratory methods. Among the peculiarities of the epidemics: the low rate of endemic morbidity, the seasonal and preseasonal peaks, the very high implication of infantile population in influenza A(H3N2), A(H1N1) and B virus circulation, as well as the high level of mass specific humoral protection against these viruses. Elements of epidemiologic prognosis are suggested for 1991. Opportunity of vaccine prophylaxis using WHO recommended virus strains of the three types: A(H3N2), A(H1N1) and B, for risk groups is discussed.

Comparative study of the immunogenicity of aqueous versus aluminium phosphate adsorbed split influenza vaccine C.I.

The antibody responses induced by the split influenza vaccine adsorbed on aluminium phosphate and the corresponding, nonadsorbed vaccine, both prepared in the Cantacuzino Institute, were studied in subjects belonging to three different age groups: 3-6, 10-15 and over 60 years of age, respectively. In all age groups the immunogenicity of the two vaccine preparations was similar, being uninfluenced by the level of preexisting antibodies. The immunogenicity of both vaccines was similar even in children considered to be non-primed. There were no differences in the persistence and specificity of antibodies induced by the two vaccines. No significant enhancement of the immunogenicity by aluminium phosphate was observed.