Karl Heinz Dr. Schmidt-Ruppin

Genital herpes in guinea-pigs. An experimental model with herpesvirus hominis.

The differentiation of herpesvirus hominis (HVH) into two serological types 1 and 2 (1), of which t tVH2 is predominantly found in genital herpes (2), the increasing incidence of genital herpes in man and certain evidence implicating HVH2 in carcinoma of the cervix (e.g. 3, 4, 5) have stimulated efforts to elaborate a suitable experimental model of genital herpes. Studies in mice have yielded no satisfactory results (6, 7). For some years, we have been endeavouring to develop a model of genital infection in other species of animal. NA~MIAS et. al. (8) have meanwhile reported on positive results in monkeys, which have been confirmed by other authors (9, 10, 11). The results we have obtained so far are summed up below: In our initial experiments, male (preputium and penis) and female (intravaginal) guinea-pigs, adult rabbits and beagle-dogs, oestradiol-progestercne primed juvenile female rabbits, rats and mice, were inoculated with HVH2/Angelotti 1, grown in HeLa cell culture. None of the male animals showed any symptoms of genital infection. In female beagles and adult rabbits, slight transient local symptoms were observed. In mice only encephalitis developed in about 30 per cent of the animals. Clearly positive symptoms were found in female guinea-pigs. In these, strain differences were seen between albino (Pirbright) and eoloured animals in that albinos proved more sensitive to the infection (see Table). The method of infection adopted in female guinea-pigs (i50--200 g body weight) was developed as a model for genital herpes. After slight abrasion of the vaginal mucosa, a small piece of fibrin foam (SEvAc, Prague), measuring 10 • 5 • 4 ram, was introduced into the vagina. The foam was impregnated with various PFU of

Herpes genitalis in guinea-pigs. I. Kinetic study in infection with Herpesvirus hominis type 2.

SummaryThe kinetics of virus replication after vaginal infection of guinea-pigs with HVH 2/Angelotti were studied in relation to the appearance of local and general symptoms. Most virus was isolated from the genital tract 24–48 hours post infection. Virus was first isolated from the spinal cord 48–72 hours post infection. Penetration into the brain only occurred occasionally, and later. Under the experimental conditions employed, no virus was found in the blood, spleen, kidneys, adrenals or inguinal lymph nodes. The local symptoms (typical genital herpes) and the general symptoms (paralysis and death) started after maximum virus replication had been reached and seemed to be a consequence of neural, rather than of haematogenic or lymphogenic spread.

Herpes genitalis in guinea-pigs. II. Morphological studies in female guinea-pigs infected with Herpesvirus hominis type 2.

SummaryGross and microscopial morphological changes developing in female guinea-pigs after vaginal infection with HVH 2/Angelotti were studied. In the mucosa of the external genital tract there were inflammatory changes with formation of intra-epithelial vesicles, erosions and ulcerations. In the late stages of the infection signs of inflammatory dysplasia were also observed. The infection spread into the nervous system and produced characteristic inflammatory changes. The inflammation began as a bilateral posterior myelitis and ascended in the course of infection through the upper spinal-cord towards the brain-stem. The morphological changes were preceded by increased virus replication in the respective tissues and were correlated in time with clinical symptoms. The morphological changes seen at the site of inoculation in the external genital tract of the guinea-pig bore a certain resemblance to those seen in some cases of human infection with the same type of virus.

CGP 6809, a sugar-containing nitrosourea derivative: pharmacological and physicochemical properties.

SummaryCGP 6809 is a water-soluble nitrosourea derivative with quite distinct chemical and biological properties as compared with the well-known representatives of this class of compounds. It is related to the antibiotic streptozotocin, from which it is distinguished in the structure of the sugar moiety and the position of the methylnitrosourea residue. CGP 6809 possesses practically the same alkylating potential as streptozotocin; however, its carbamoylating activity is comparable with that of CCNU. In contrast to other nitrosourea derivatives, CGP 6809 showed relatively little activity in murine leukemias but was markedly active in solid transplantable melanomas (Harding-Passay, B16), in the 11095 prostate carcinoma, and in a substrain of Yoshida hepatoma (AH 7974) resistant to BCNU and CCNU. In the Ehrlich and Yoshida ascitic tumors complete responses were seen with no toxic death. Dose-dependent activity was found in the human lung carcinoma MBA 9812 and almost complete growth inhibition was achieved in the human melanoma WM 47 by both the oral and parenteral routes of administration. However, mammary tumor lines (Ca 755, 2661/61, R-3230AC), the Guerin-T8 uterus epithelioma, and the Rous sarcoma/S-R proved to be relatively refractory to this drug. This was also the case for the Lewis lung carcinoma implanted i. m. or s. c. However, development of lung metastases was markedly inhibited. Combination therapy using CGP 6809 with cyclophosphamide, 5-fluorouracil, or chlorambucil in the same model led to partial responses of the primary tumor as well as almost total eradication of lung metastases.