Ethyl-2-cyanoacrylate was applied to the cortex of rabbits to evaluate its bioadhesive and histotoxic behavior. The animals were killed at 4 or 10 days. Half of the animals were pretreated with dexamethasone. Our results indicate that the application of ethyl-2-cyanoacrylate to brain tissue produced severe superficial cortical necrosis but not bioadhesion. Pretreatment with steroids did not provide a significant protective effect.

This report describes a spectrum of cytotoxic and teratogenic effects induced in late stage fetal and early suckling hamsters and rats with the antiviral drug Ribavirin. The adverse effects include granuloprival cerebellar hypoplasia, epidermal defects, cytolysis of the enamel organ of tooth germs, and disorganization of the retina. These effects point to the vulnerability to the synthetic nucleoside of tissues with active DNA synthesis attending cell replication, and indicate that the therapeutic index, i.e. the margin between beneficial and toxic effects of ribavirin, may be narrow or even nonexistent in the fetus and neonate.

We describe induction of obstructive hydrocephalus by intra-amniotic inoculation of parainfluenza type 2 virus into 10- to 12-day pregnant hamsters. As determined by cytoplasmic inclusions, specific immunofluorescence, cytopathic effects, inflammation, and/or gross and microscopic lesions, 144 of 264 exposed fetuses were infected. Fetuses harvested at term showed initial infection of yolk sac endoderm, transmission to fetuses via oronasal portals, and early spread along respiratory mucosa. Mild meningoencephalitis, principally involving ependyma and usually sparing brain parenchyma, was also observed in 58 animals. While pneumonitis tended to regress without significant sequellae, destruction of ependyma led to gliovascular outgrowth over ventricular walls, adhesions, and aqueductal stenosis. Ultimately, as observed in four animals, obstructive hydrocephalus resulted. The aqueductal lesion, a consequence of repair, resembled a developmental rather than a postinfectious defect. This is the second example of the experimental induction of this entity by an intrauterine systemic viral infection, the other causative agent being mumps. These two sets of studies, which bear close comparison, support the postulate that congenital hydrocephalus in humans may be the result of intrauterine infection by common viruses, which only infrequently invade the developing nervous system and induce mild, self-limited, but strategically localized disease.

This study focused on the unique nature of K-virus pneumonitis in suckling mice. This process, rather than being a conventional pneumonitis, is characterized by viral replication and cytopathic effects restricted exclusively to pulmonary endothelium. The selective viral attack on this air-blood interface suggests that K-virus is an endotheliotrope that requires a richly oxygenated intracellular milieu for replication. This possibility has been explored by studies of the course of K-virus infection in suckling mice under conditions of normal (21 per cent), increased (40 per cent), and decreased (10 per cent) 02 content of inspired air. The absence of critical modulating influences of these varied environmental conditions rules out a significant role of tissue 02 concentrations as determinants of the selective tropism of K-virus.

Intracerebral inoculation of mouse cytomegalovirus (MCMV) into neonatal and young suckling mice induces severe meningoencephalitis in which neuronal involvement and giant cell formation are prominent features. Characteristic markers for cell parasitism are hematoxylinophilic nuclear inclusions with a broad surrounding halo zone and globular phloxinophilic cytoplasmic inclusions. A remarkable feature of the polykaryocytes formed by virus-induced fusion of neurons is the bimodal nuclear population, composed of normal-appearing and inclusion-bearing nuclei. This dual population points to the recruitment of noninfected by infected cells into a syncytium by action of virus upon cell membranes and suggests a ready means of intraparenchymatous spread by a virus which is largely cell associated. Viral neurocytotropism involves postmitotic Purkinje cells as well as differentiated maturing cerebral cortical neurons and undifferentiated intermitotic cerebellar external germinal cells. This virus-cell relationship indicates that cell division is not a prerequisite condition for activation of MCMV.

This report describes the investigation of the pathogenesis of an unusual sequel of reovirus encephalitis in suckling rats. Intracerebral inoculation of reovirus types 1, 2, and 3 into suckling rats induced, in addition to viral cytoplasmic inclusions, distinctive intranuclear bodies corresponding most closely to those designated by Cowdry (1934) as type B inclusions. The latter were seen in cells free of reovirus inclusions and unlike the conventional reactions to these viruses, were readily observed in weanlings, were unassociated with inflammatory features, and persisted for extended periods without cytolytic effects. To test the hypothesis that another viral agent was responsible for production of these nuclear changes, attempts were made to induce this change by inoculation of tissue preparations obtained from infected animals beyond the period of active reovirus encephalitis. These were uniformly negative. Furthermore, strains of reovirus from various sources all induced this nuclear change. Electron microscopic studies of the choroid plexus yielded no evidence of a second virus but instead demonstrated that the inclusions were composed of granular aggregates, sometimes enclosed in lamellar membranes, characteristic of the structures called nuclear bodies. These studies expand the perspectives of the nature and pathogenesis of this cellular lesion and provide an optical indicator which facilitates its identification and study. They suggest that the well-known Cowdry B inclusion has as its electron microscopic counterpart, the nuclear body.

blood, mammary glands, and milk removed from the stomachs of sucklings all had infectivity titers of approximately 10-3-10-4/0.1 ml when tested in rat embryo tissue cultures. Rat virus continued to be recoverable for a number of days after the appearance of circulating (HAI) antibodies. Proliferation of virus in mammary tissue and excretion of virus brought to the gland by the bloodstream are postulated to have been the chief mechanisms involved in the virolactia.

AbstractReovirus type 3 was able to induce various effects in fetuses depending on the period of gestation pregnant hamsters were inoculated. Inoculations on gestation days 1–5 resulted in a high rate of fetal deaths. Fetuses of females inoculated on days 9–11 all became infected, but survived and developed normally. Reovirus proliferated to high liters in placentas and uteruses and was recovered from amniotic fluids in higher titer than from fetuses. Presence of phloxinophilic cytoplasmic inclusion bodies in pathologic studies revealed a spectrum of fetal infection ranging from mild involvement of the epidermis and ora mucosa to widespread systemic disease involving skin, visual organs, skeletal muscle, and neural tissues as well as voluntary muscles. These findings were substantiated by immunofluorescence studies. Throughout these experiments pregnant animals remained in good health in spite of having relatively high and sustained viremias. In view of the ubiquitous distribution of reoviruses in nature, and their lack of interspecies differences, observations of their ability to induce serious transplacental infections as well as hydrocephalus in laboratory animals point to the desirability of continued study of their potential role in the etiology of human disease.

Multiple contributory factors have been postulated in the pathogenesis of hemorrhagic encephalopathy of the rat, an entity induced by rat virus infection of sucklings. These include: (1) the direct attack of virus upon vascular endothelium with resultant thrombotic and hemorrhagic effects; (2) the triggering of consumptive coagulopathy by the vascular injury; and (3) the production of a deficiency coagulopathy secondary to viral hepatitis. This report describes a new feature of rat virus infection, the involvement of the pool of developing megakaryocytes. This cellular lesion, although unsupported by evidence of depressed platelet levels, or disturbed platelet function, suggests that a direct viral attack upon platelet-forming elements may be an additional contributory factor in the pathogenesis of hemorrhagic encephalopathy. The complex of pathogenetic factors for hemorrhagic encephalopathy of the rat indicates that this entity offers an excellent experimental model for study of the general problem of the pathophysiology of disturbances of blood coagulation in virus infections.

Transplacental infections with MVM were studied in hamsters, rats, and mice. The most striking infections were in hamsters in which infected fetuses developed high titers of virus, then died, and were resorbed. Only a few fetuses out of each litter became infected, the majority remaining alive, well, and free of infection. The situation in pregnant mice, which are natural hosts of this agent, was different. In them parenteral inoculations produced no discernible effects on either mother or fetuses. But infected fetuses with high titers of virus were recovered from other females at term. In neither hamsters nor mice were instances found of placental infection unaccompanied by fetal infection. Why only a small percent of inoculated pregnant mice developed transplacental infections was not clear. Rats free of immunity and hence susceptible to parenteral inoculations were not found. Intrafetal inoculations of rats revealed, however, that MVM can proliferate in fetuses and then persist for weeks following birh without inducing detectable illness. Histologic studies revealed sparse but characteristic intranuclear inclusions in some animals but it was evident in others that MVM can be present in substantial titers in an absence of apparent histologic change. After direct inoculation of some rat and hamster fetuses generalized severe disease resulted, with replicating tissues being the major viral targets, as has been previously observed in infections with other intrauterine parvoviruses. Here large infectious doses were thought to be responsible for the special effects observed.