Gamma interferon impedes the establishment of herpes simplex virus type 1 latent infection but has no impact on its maintenance or reactivation in mice.

Murine models of gamma interferon (IFN-gamma) deficiency demonstrate the role of this cytokine in attenuating acute herpes simplex virus (HSV) disease; however, the effect of IFN-gamma on the establishment and maintenance of neuronal latency and viral reactivation is not known. Using the IFN-gamma knockout (GKO) model of IFN-gamma deficiency and sensitive quantitative PCR methods, we show that IFN-gamma significantly reduces the ganglion content of latent HSV-1 in BALB/c mice, which in turn delays viral time to reactivation following UV irradiation. Similar effects were not seen in the C57BL/6 strain. These results indicate that IFN-gamma significantly attenuates latent HSV infection in the mouse model of ocular infection but has no impact on the maintenance of latency or virus reactivation.

Treatment of HSV-1 infection with immunoglobulin or acyclovir: comparison of their effects on viral spread, latency, and reactivation.

We compared immunoglobulin (IgG) and acyclovir (ACV) therapies on the establishment, maintenance, and reactivation from latency of HSV-1(McKrae) in a mouse ocular infection model. Mice were given one intraperitoneal (IP) dose of human IgG 24 h after infection (Day 1 p. i.) or ACV in the drinking water from Days 1 to 7 p.i. Both treatments allowed similar percentages of mice to survive the infection and decreased ocular virus shedding as compared with untreated controls. At most time points, there were no differences between IgG- and ACV-treated animals with respect to tissue virus titers or in the rates of virus reactivation during explant cocultivation. However, after ultraviolet exposure, HSV reactivated in 30% of ACV-treated mice compared with 90% of IgG-treated mice (P = 0.02). Also by quantitative PCR, we found more latent HSV-1 DNA copies in IgG-treated mice compared with those given ACV (P = 0.02). IgG treatment protects mice from HSV-1 infection essentially as well as ACV does. Nonetheless, it permits higher levels of latent infection and subsequent in vivo reactivation. These studies have implications for the mechanism by which IgG functions to attenuate HSV infections and for its potential value as a therapeutic agent in humans.

Lack of interleukin-6 (IL-6) enhances susceptibility to infection but does not alter latency or reactivation of herpes simplex virus type 1 in IL-6 knockout mice.

The ability of the pleotropic, proinflammatory cytokine interleukin-6 (IL-6) to affect the replication, latency, and reactivation of herpes simplex virus type 1 (HSV-1) in cell culture and in IL-6 knockout (KO) mice was studied. In initial studies, we found no effect of exogenous IL-6, monoclonal antibodies to IL-6, or monoclonal antibody to the IL-6 coreceptor, gp130, on HSV-1 replication in vitro by plaque assay or reactivation ex vivo by explant cocultivation of latently infected murine trigeminal ganglia (TG). Compared with the wild-type (WT) mice, the IL-6 KO mice were less able to survive an ocular challenge with 10(5) PFU of HSV-1 (McKrae) (40% survival of WT and 7% survival KO mice; P = 0.01). There was a sixfold higher 50% lethal dose of HSV-1 in WT than IL-6 KO mice (1.7 x 10(4) and 2.7 x 10(3) PFU, respectively). No differences were observed in titers of virus recovered from the eyes, TG, or brains or in the rates of virus reactivation by explant cocultivation of TG from latently infected WT or KO mice. Exposure of latently infected mice to UV light resulted in comparable rates of reactivation and in the proportions of WT and KO animals experiencing reactivation. Moreover, quantitative PCR assays showed nearly identical numbers of HSV-1 genomes in latently infected WT and IL-6 KO mice. These studies indicate that while IL-6 plays a role in the protection of mice from lethal HSV infection, it does not substantively influence HSV replication, spread to the nervous system, establishment of latency, or reactivation.

The comparative effects of famciclovir and valacyclovir on herpes simplex virus type 1 infection, latency, and reactivation in mice.

Infections by herpes simplex virus (HSV) cannot yet be eliminated, but the severity of the disease can be reduced. Two newer drugs with established efficacy for such infections, famciclovir and valacyclovir, were tested in a mouse eye model of HSV infection. Both drugs significantly reduced mortality and titers of virus shed from the eyes of mice infected with an otherwise lethal dose of HSV type 1 (HSV-1). Similar titers of HSV-1 were found in the eyes, ganglia, and brains of treated animals. Although valacyclovir reduced the latent viral DNA load better in these studies than did famciclovir, rates of reactivation by explantation and UV exposure were the same. Thus, in this study, famciclovir and valacyclovir were equally effective in limiting the virulence and spread of HSV-1, despite their biochemical and pharmacologic differences.

Defective entry of herpes simplex virus types 1 and 2 into porcine cells and lack of infection in infant pigs indicate species tropism.

We have determined if a defect at entry of the human pathogen herpes simplex virus type 1 (HSV-1) into cultured porcine cells extends to HSV-2 and if the poor susceptibility of porcine cells for these viruses is indicative of in vivo species tropism. HSV-1 replicates poorly in swine testis (ST) and other porcine cells which lack a functional non-heparan sulphate receptor(s) required for virus entry. By several criteria, ST cells resist infection by either HSV-1 or HSV-2. Infection can be restored if normal entry is bypassed by PEG-mediated virion-cell membrane fusion. Neither HSV serotype infects, replicates or produces clinical symptoms in infant pigs. No virus was isolated from any of multiple sites and seroconversion did not occur. The in vitro defect in porcine cells blocking HSV entry correlates with, and is likely to be at least partly responsible for, in vivo resistance of pigs to infection.

Prevalence of anaemia in the Curacao health study: its relationship with socio-economic status and self-reported health status - abstract

The main goal of the Curacao Health Study (CHS), which is cross-sectional in design, is to give insight into the determinants of health in the Curacao population. Anaemia often occurs as a secondary manifestation of underlying conditions. In addition, socio-economic factors affect health-status and, anaemia can also be related to these variables. Prevalence of anaemia for the population in the CHS 15.0 percent. Of the males 10.5 percent were anaemic, while 18.1 percent of the females were anaemic. Microcytic/hypochromic anaemia accounted for 28.8 percent of the anaemias, while normochromic anaemias accounted for 69.2 percent and macrocytic anaemias for 2.0 percent of all anaemias. Prevalence of iron deficiency anaemia (IDA) was 7.2 percent and 0.5 percent in the female and male populations, respectively. An inverse relationship was noted between socio-economic status and anaemia. A relationship was also evident between malignant neoplastic conditions, menstrual and severe kidney disorders and anaemia (AU)

Prevalence of lipid risk factors for atherosclerosis in the Curacao Health Study: interactions with demographic and socio-economic variables - asbtract

The Curacao Health Study is a cross-sectional population-based study designed to give insight into the determinants of health on Curacao. This study presents prevalence data for lipid risk factors and interactions with demographic and socio-economic variables. Serum was collected from 1001 (44.5 percent) respondents included in the CHS study. These respondents were representative for all respondents. Cholesterol, HDL-cholesterol and triglycerides were measured and LDL-cholesterol was calculated. Cholesterol levels increased significantly in women > 50 years of age, as did LDL-cholesterol levels. HDL-cholesterol was higher in women than in men (52 ñ 13 mg/dl vs 48 ñ 15 mg/dl). Mean total and LDL-cholesterol levels were comparable to Western European and Northern American populations. Multiple regression indicated that race (Black vs non-Black) did not contribute to cholesterol levels, whereas education, living in the East District, age, and gender did. These associations need further study before definitive conclusions can be drawn. We conclude that lipid risk factors are as prevalent on Curacao as in most Western societies (AU)

Effect of intravenous and oral calcium antagonists (diltiazem and verapamil) on sustenance of atrial fibrillation.

Both verapamil and diltiazem are used to control ventricular response during atrial fibrillation (AF). Their effect on the maintenance of AF is not known. The effects of the intravenous and oral administration of verapamil and diltiazem were investigated in 35 patients, 18 with (group I) and 17 without (group II) documented paroxysmal AF. Programmed electrical stimulation, either extra-stimuli or burst atrial pacing, was used to induce AF. In group I, the mean values of the duration of AF before and after the intravenous and oral administration of the calcium antagonists were 31 +/- 12, 112 +/- 49 and 69 +/- 25 minutes, respectively. For group II, the values were 5 +/- 3.4, 39 +/- 13 and 14 +/- 7 minutes, respectively. The differences were statistically highly significant (p less than 0.001), after both oral and intravenous administration compared with the baseline value in both groups. The data suggest that both intravenously and orally administered calcium antagonists enhance sustenance of electrically induced AF, especially in patients with spontaneous arrhythmia. Thus, in patients with paroxysmal AF, verapamil or diltiazem should be administered cautiously, because these drugs may prolong the duration of arrhythmia. Further studies are warranted to investigate the role of calcium antagonists in spontaneously occurring paroxysmal AF.

Efficacy and safety of intravenous and oral diltiazem for Wolff-Parkinson-White syndrome.

The electrophysiologic effects and safety of diltiazem administered either intravenously or orally were studied in 14 patients with Wolff-Parkinson-White syndrome during orthodromic reentrant tachycardia and atrial fibrillation (AF). Anterograde and retrograde effective refractory periods of the accessory pathway did not change significantly from baseline during either i.v. or oral administration. Administration by either route prevented induction of sustained reentrant tachycardia in 8 patients. In 6 patients, the reentrant tachycardia was either nonsustained (2 patients) or sustained at much slower rates than the baseline rates (mean +/- standard deviation, baseline, 290 +/- 41 ms; i.v., 355 +/- 40 ms [p less than 0.001]; and oral, 377 +/- 33 ms [p less than 0.001]). In these patients anterograde atrioventricular conduction was prolonged significantly from the mean baseline value of 163 +/- 36 ms to 212 +/- 35 ms with i.v. administration (p less than 0.005) and 225 +/- 33 ms with oral administration (p less than 0.005). Retrograde conduction via the accessory pathway did not change significantly after administration of diltiazem. The shortest preexcited RR intervals during AF were significantly reduced during i.v. but not during oral administration: control, 327 +/- 47 ms; i.v., 270 +/- 28 ms (p less than 0.001); and oral, 323 +/- 44 ms (difference not significant). In 5 patients AF was sustained for a mean of 20 minutes after i.v. and for 12 minutes after oral administration (p less than 0.20), compared with a baseline mean value of 0.83 minute.(ABSTRACT TRUNCATED AT 250 WORDS)