Suppression of humoral antibody formation against HSV is not only induced by replicating Herpes simplex virus type 2 (HSV-2) but also by the defective strain ANG and the deletion mutant 1301 of Herpes simplex virus type 1 (HSV-1). Moreover, ts-mutants A, H, K, S, 1201 and 1208 of HSV-1 as well as some ts-mutants of HSV-2 and "defective-interfering" particles of HSV-1 after high multiplicity of infection-passages induced suppression. Treatment of infected mice with ACG reduced antibody-formation but did not result in suppression. UV-irradiation of the antibody producing strain Len of HSV-1 strongly reduces antibody formation and induces suppression. Experiments using a series of intertypic recombinants showed the suppressing activity to be spread over the whole genome of HSV-2. It is concluded that suppression is induced by more than one region of the genome of HSV-2 and by incomplete replication of HSV-1 and 2.

The objective was to assess the single- and multiple-dose pharmacokinetics of levodopa and 3-O-methyldopa following administration of a new dual-release and conventional slow-release formulation of levodopa/benserazide in the dose ratio of 4:1. In an open-label, two-way cross-over study, 20 healthy volunteers were randomized to receive first either Madopar DR or Madopar HBS for 8 days. Then they crossed over to the other formulation. A first dose of 200 mg levodopa and 50 mg benserazide ('250' mg) was given on day 1, '125' mg t.i.d. on the subsequent 6 days (days 2-7), followed by '250' mg on day 8. The two treatment periods of 8 days were separated by a wash-out period of at least 7 days. Blood samples were taken at specific times over a 12-hour period (day 1) or a 36-hour period (day 8). Plasma concentrations of levodopa and 3-O-methyldopa were measured by high-performance liquid chromatography for pharmacokinetic evaluation. The pharmacokinetics of levodopa after a single-dose administration (day 1) of Madopar DR and Madopar HBS were significantly different as reflected by the respective mean values of maximum plasma concentration (C(max) 1.99 vs. 0.82 mg x l-1), time to reach maximum concentration (t(max) 0.7 vs. 2.6 h) and area under the plasma concentration-time curve (AUC(0- infinity ) 4.52 vs. 3.18 mg x h x l-1). The respective values after multiple doses (day 8) were: C(max) 1.98 vs. 0.93 mg x l-1, t(max) 0.7 vs. 2.3 h and AUC(0-infinity ) 4.84 vs. 3.96 mg x h x l-1. The relative bioavailability (Madopar DR vs. Madopar HBS) was 1.73 on day 1 and 1.32 on day 8. Bioequivalence could not be demonstrated for log-transformed data of AUC and C(max) within a predefined range of 80-125 and 70-143%, respectively. In conclusion, the observed differences in C(max), t(max) and AUC are consistent with a faster rate and higher extent of levodopa absorption after administration of Madopar DR. Statistical evaluation of these kinetic data showed that Madopar DR is not bioequivalent to Madopar HBS.

The mechanism of herpes simplex virus (HSV)-2-induced immunosuppression was analysed by determination of the number of IgM and IgG antibody-secreting B cells in female BALB/c mice using an immunospot assay. Primary HSV-1 or -2 as well as homologous or heterologous booster infections at different times were performed. In accordance with earlier results on humoral antibody generation, in contrast to HSV-1, HSV-2 induced only very low numbers of antibody-producing B cells in dose-response experiments. They appeared late after infection compared to HSV-1. Despite a homologous humoral booster reaction against HSV-1 at day 8 no IgM- or IgG-secreting cells in the spleen could be detected. This non-reactivity of the spleen had vanished 10 days later, when secondary reactions of B cells could be observed. Secondary infections with a high homologous dose of HSV-2 after a low primary dose produced only a low booster response of IgG-secreting B cells. Suppression of humoral antibody production induced by HSV-2 (high dose) waned after more than 50 days, indicating that the HSV-2-induced suppression did not impair antigen presentation or memory cell generation.

HSV-2 infections suppress the antibody response to HSV-1 but do not impair the mouse cytomegalo virus (MCMV) antibody generating system. In contrast, the sheep red blood cell (SRBC) IgM response is impaired by preinfections with HSV-2 but not with HSV-1. From the time kinetics of this suppression it can be concluded that only a certain submechanism "spills over" to the SRBC system. MCMV suppresses the antibody formation induced by HSV-1.

Intraperitoneal infection of mice and rats by herpes simplex virus type 2 (HSV-2) but not type 1 (HSV-1) resulted in suppression of antibody formation on subsequent challenge with HSV-1 or HSV-2. Application of silica considerably enhanced antibody formation after primary HSV-1 infection, but only slightly after primary HSV-2 infection. Suppression induced by HSV-2 was, however, reduced significantly by injection of silica 21 days later, on the day of the second injection of HSV-2. Suppression could be detected soon after infection by HSV-2. The degree of this suppression depended on the dose of the injected virus and was abolished by u.v. irradiation of the virus prior to inoculation. Likewise the weak antibody response induced by HSV-2 was abolished for both neutralizing and ELISA antibodies. Infections with HSV-1 evoked considerable numbers of HSV-specific antibody-producing B cells, when assessed by an enzyme-linked immunospot assay. The B cell response to HSV-2, however, was very weak. Silica considerably enhanced the number of specific antibody-producing B cells only during primary HSV-1 infections. The present results in combination with earlier data demonstrate the central role of macrophages, which seem to be the primary target affected by silica, for enhancement and suppression of HSV-induced antibody generation.

British Journal of Addiction to Alcohol & Other DrugsVolume 62, Issue 1-2 p. 61-69 Damage to the Liver of Alcoholics in Gamma-Scintigraphic Pictures Ŝ. SPAVENTI, Ŝ. SPAVENTI *Institute of Radiology and Nuclear Medicine, General Hospital, Zagreb, Vinogradska c. 29, YogoslaviaSearch for more papers by this authorVI. HUDOLIN, VI. HUDOLIN †Centre for Study and Treatment of Alcoholism, General Hospital, Zagreb, Vinogradska c. 29, YugoslaviaSearch for more papers by this authorM. RUDAR, M. RUDAR †Centre for Study and Treatment of Alcoholism, General Hospital, Zagreb, Vinogradska c. 29, YugoslaviaSearch for more papers by this authorI. GABELIĈ, I. GABELIĈ †Centre for Study and Treatment of Alcoholism, General Hospital, Zagreb, Vinogradska c. 29, YugoslaviaSearch for more papers by this authorB. METZGER, B. METZGER *Institute of Radiology and Nuclear Medicine, General Hospital, Zagreb, Vinogradska c. 29, YogoslaviaSearch for more papers by this author Ŝ. SPAVENTI, Ŝ. SPAVENTI *Institute of Radiology and Nuclear Medicine, General Hospital, Zagreb, Vinogradska c. 29, YogoslaviaSearch for more papers by this authorVI. HUDOLIN, VI. HUDOLIN †Centre for Study and Treatment of Alcoholism, General Hospital, Zagreb, Vinogradska c. 29, YugoslaviaSearch for more papers by this authorM. RUDAR, M. RUDAR †Centre for Study and Treatment of Alcoholism, General Hospital, Zagreb, Vinogradska c. 29, YugoslaviaSearch for more papers by this authorI. GABELIĈ, I. GABELIĈ †Centre for Study and Treatment of Alcoholism, General Hospital, Zagreb, Vinogradska c. 29, YugoslaviaSearch for more papers by this authorB. METZGER, B. METZGER *Institute of Radiology and Nuclear Medicine, General Hospital, Zagreb, Vinogradska c. 29, YogoslaviaSearch for more papers by this author First published: March 1967 https://doi.org/10.1111/j.1360-0443.1967.tb05331.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Volume62, Issue1-2March 1967Pages 61-69 RelatedInformation