Virucidal and chlamydicidal activities of eye drops with povidone-iodine liposome complex

Povidone-iodine (PVP-I) is a broad-spectrum microbicide with in vitro activity against bacteria, viruses, fungi and protozoans. A 5% solution of PVP-I proved to be highly effective in ophthalmic surgery for the prophylaxis of endophthalmitis. For the antiseptic treatment of eye infections a novel application form of PVP-I has been developed by using a PVP-I liposome complex which demonstrated an excellent antimicrobial efficacy. In this study it could be shown that the novel liposomal formulations containing 2.5 or 5% PVP-I were as active as the aqueous solution against herpes simplex virus type 1, adenovirus type 8, coxsackievirus A9 and Chlamydia trachomatis in cell culture referring to equal PVP-I concentrations. Long-term cytotoxicity experiments demonstrated a moderate cytotoxicity for both formulations with a better tolerability of the liposomal PVP-I formulation compared with the aqueous solution. There is no evidence for a genotoxic activity of these agents.     

Differential morphological reaction of experimental CNS tumour clonesin vitro to dibutyryl cyclic AMP or serum-free medium,resp.

Six clones from methylnitrosourea (MNU) or ethylnitrosourea (ENU) induced tumours obtained in the nervous system of the rat were cultured in serum-free medium or treated with dibutyryl cyclic AMP (db cAMP) in vitro. All clones originated from longterm cultures. Three clones forming sarcomas after syngeneic transplantation showed only very slight changes following treatment, whereas the three glioma clones showed striking alterations. They formed long processes or showed rounding of their perikarya. In serum-free medium the cellular shape is intermediate between that seen in normal conditions and the seen in db cAMP treated cultures. The altered cultures resemble the primary cultures of the respective tumours. The relationship of these alterations to tumour types are discussed.     

Cytogenetic genotoxicity of anti-herpes purine nucleoside analogues in CHO cells expressing the thymidine kinase gene of herpes simplex virus type 1: comparison of ganciclovir, penciclovir and aciclovir

The three anti-herpes nucleoside analogues ganciclovir, penciclovir and aciclovir were investigated as to their recombinogenic [sister chromatid exchange (SCE) inducing] and clastogenic activity in CHO cells expressing the thymidine kinase gene of HSV-1, which is a precondition of therapeutic activity of these drugs. The compounds were applied for the duration of one cell cycle and cytogenetic end-points were measured between 0 and 42 h after exposure. Although the nucleoside analogues are quite similar with respect to chemical structure, they differ basically in their genotoxic potency, aberration types induced as well as the time course of chromosomal damage. Aciclovir induced SCEs and chromosomal aberrations immediately after exposure but only in a concentration range much higher than that reached in blood plasma during anti-herpes therapy. The direct genotoxic activity is explained by the obligate chain terminating property of aciclovir upon incorporation into genomic DNA. On the other hand, genotoxic damage caused by ganciclovir and penciclovir is of the delayed type requiring at least one post-exposure cell cycle for its expression. Unlike aciclovir, ganciclovir is an extremely potent inducer of SCEs and chromosome breaks and translocations at concentrations far below those impairing the proliferative activity and triggering apoptosis of the target cells (as shown by our previous investigation). Penciclovir is essentially devoid of genotoxic activity. It induces SCEs only at cytotoxic/apoptotic concentrations, is only weakly clastogenic and induces premature chromosome condensation which appears to result from uncoupling of karyokinesis and cytokinesis. The genotoxic activity of ganciclovir is explained as due to repair processes triggered in the second post-exposure replication cycle at the sites of nucleoside analogue incorporation into genomic DNA. The findings have considerable implications with respect to the use of ganciclovir or other antiviral drugs in suicide gene therapy of malignant diseases.     

Triapten ointment in the treatment of herpes genitalis in the female

We report about the therapy of Herpes simplex infections. We applied triapten ointment topically in 166 women with relapse illnesses. In cases with early application we cured 80 per cent of vulvitis herpetica. In 17 per cent we observed side effects we tried to clarify the reasons.     

Serine hydrolases activate/inactivate trisubstituted nitrosoureas in dependence on intra- and extracellular enzyme location: an SCE study in Chinese hamster V79-E cells

Trisubstituted nitrosoureas are very stable in aqueous systems.But they are potent genotoxins in Chinese hamster V79-E cells,if no exogenous metabolizing system is added, and the mechanismof their genotoxic and carcinogenic activity has been largelyunknown. This investigation shows that the sister-chromatid-exchange(SCE)-inducing capacity of 1,3-dimethyl-3-phenyl-1-nitrosourea(DMPNU) is eliminated by adding dlisopropylfluorophospbate (DFP)or porcine liver carboxylesterase to the incubation system.These effects are caused by two different mechanisms: (i) DFPinhibits endogenous amidases existing in V79-E cells, thus preventingthe intracellular decomposition, which means an activation;and (ii) exogenous carboxylesterase cleaves DMPNU extra cellularly,and the genotoxic decomposition product is obviously too short-livedto reach a critical intracellular target. A second trisubstitutednitrosourea, 3,3-diethyl-1-methyl-1-nitrosourea (DEMNU), whichis mainly activated by monooxygenases, but in the absence ofan exogenous metabolizing system also induces SCEs in V79-Ecells, was studied in the same way. It was found that the ‘direct’genotoxicity of DEMNU may be inhibited by DFP as well, but carboxylesterasedecomposes this trialklynitrosourea with a much lower efficiencythan DMPNU suggesting a low substrate affinity. The SCE-inducingcapacity of both compounds is strongly influenced by the presenceof calf serum in the culture medium. The nature of the serumfactor is still unknown. Pathways for the amidase catalysisof DMPNU and for the activation of DEMNU by monooxygenases andamidases are proposed and discussed with respect to the topicalor systemic carcinogenicity of these agents.     

Comparative studies on thein vitro andin vivo morphology of clones of experimental CNS tumours in the rat

Summary Two sarcomas, one neurosarcoma and one polymorphous tumour of uncertain classification of the central nervous system of the rat induced by N-nitrosomethylurea or ethylnitrosourea were the source of 14 clones. The cytomorphology and the aggregation pattern of the clonesin vitro are described. The malignancy and histology were checked by homologous transplantation. All the clones formed sarcoma-like structuresin vivo, but it was difficult to decide whether these neoplasias were real sarcomas or very dedifferentiated glial tumours. The differences in cytology observedin vitro were greater than the histological differencesin vivo.     

Establishment and cidofovir sensitivity of a cell line from a heart transplant recipient with multiple cutaneous tumors

A new cell line, designated as Tuwei00, is described. It originated from an Epstein-Barr virus-positive skin tumor biopsy of a heart transplant recipient, whose numerous cutaneous neoplasms were treated with the antiviral drug cidofovir what caused at least transient remissions. The cell line was established in vitro and maintained for more than 70 passages. Cells of early passages were characterized by a slower growth, the inability to form colonies and a higher sensitivity to cidofovir. After overcoming a crisis, the cells grew faster, to a higher density and were able to form adherent colonies from single cells as well as colonies in soft agar. Chromosome analysis showed diploidy/hyperdiploidy at the earlier and hypodiploidy at the later passages. Sensitivity to cidofovir was distinctly higher in early passages of Tuwei00 cells than in later passages and was characterized by distinct decline of cell survival after long term cidofovir exposure. Established normal human keratinocytes, HaCaT cells, which were checked for comparison, showed a low cidofovir sensitivity similar to late passage Tuwei00 cells.