Simian Varicella Virus Infection of Rhesus Macaques Recapitulates Essential Features of Varicella Zoster Virus Infection in Humans

Simian varicella virus (SVV), the etiologic agent of naturally occurring varicella in primates, is genetically and antigenically closely related to human varicella zoster virus (VZV). Early attempts to develop a model of VZV pathogenesis and latency in nonhuman primates (NHP) resulted in persistent infection. More recent models successfully produced latency; however, only a minority of monkeys became viremic and seroconverted. Thus, previous NHP models were not ideally suited to analyze the immune response to SVV during acute infection and the transition to latency. Here, we show for the first time that intrabronchial inoculation of rhesus macaques with SVV closely mimics naturally occurring varicella (chickenpox) in humans. Infected monkeys developed varicella and viremia that resolved 21 days after infection. Months later, viral DNA was detected only in ganglia and not in non-ganglionic tissues. Like VZV latency in human ganglia, transcripts corresponding to SVV ORFs 21, 62, 63 and 66, but not ORF 40, were detected by RT-PCR. In addition, as described for VZV, SVV ORF 63 protein was detected in the cytoplasm of neurons in latently infected monkey ganglia by immunohistochemistry. We also present the first in depth analysis of the immune response to SVV. Infected animals produced a strong humoral and cell-mediated immune response to SVV, as assessed by immunohistology, serology and flow cytometry. Intrabronchial inoculation of rhesus macaques with SVV provides a novel model to analyze viral and immunological mechanisms of VZV latency and reactivation

Neuroprotective Properties of Glycosaminoglycans: Potential Treatment for Neurodegenerative Disorders

Previous studies suggest that proteoglycans and glycosaminoglycans (GAGs) may play an important role in the pathogenesis and/or alleviation of neurodegenerative disorders, including Alzheimer's disease (AD). Proteoglycans increase the formation of neurofibrillary tangles, and stimulate the aggregation of β-amyloid (Aβ). This effect, on the other hand, is believed to be competitively inhibited by certain GAGs. Over the past few years, we have examined the neuroprotective properties of Neuroparin (C3), a low-molecular-weight GAG (approx. 2.1 kDa), in animal models of lesions characteristic of AD. Neuroparin is composed of 4–10 oligosaccharides, and it is derived from heparin involving depolymerization of heparin by gamma irradiation. In our experiments, Neuroparin protected against cholinergic lesions induced by intracerebroventricular injection of a specific cholinotoxin, AF64A, in rats. Administration of Neuroparin attenuated AF64A-stimulated, low-affinity nerve growth factor receptor-immunoreactive axonal varicosities in the rat septum, and increased arborization of hippocampal CA1 neurons. Neuroparin also reduced the septal caspase 3 immunoreactivity induced by AF64A treatment. Moreover, Neuroparin reduced tau 2 immunoreactivity in the rat hippocampus, stimulated by intra-amygdaloid injection of Aβ25–35. These findings are in good agreement with our previous data indicating a neuroprotective role of GAGs. These results, plus others, all suggest that Neuroparin may possess neuroprotective properties against many of the characteristic neural lesions in AD. Since our pharmacokinetic studies revealed that Neuroparin is capable of crossing the blood-brain barrier, Neuroparin may, conceivably, open an entirely new avenue in the treatment of neurodegenerative disorders. Phase I studies have been completed, and have proven to be extremely supportive in that regard

Kreislaufstillstand in besonderen Situationen

Truhlář A, Deakin CD, Soar J, et al. Kreislaufstillstand in besonderen Situationen. Notfall + Rettungsmedizin. 2015;18(8):833-903