Regulation of cytoskeletal proteins by thyroid hormone during neuronal maturation and differentiation

Nicotine is known to have multiple effects on neuroendocrine, autonomic, and behavioral responses. Its neuroendocrine effect on the stress-responsive hormone, ACTH, depends on central pathways that act on corticotropin-releasing hormone (CRH) neurons in the paraventricular nucleus of the hypothalamus (PVN). Other CRH neurons throughout the brain also are involved in coordinating aspects of the stress response, but very little is known about the effect of nicotine on CRH neurons in extrahypothalamic regions that are involved in the autonomic and behavioral responses to stress. The current study sought to determine the extent of nicotinic activation of extrahypothalamic CRH neurons, since these neurons may be involved in mediating the central effects of nicotine. Freely moving rats were pretreated with a low dose of colchicine, infused with nicotine (0.045 mg/kg/30 s or 0.135 mg/kg/90 s, i.v.), and cardiac perfused 1 h later. Double-label immunocytochemistry identified the activated (positive for cFos protein) CRH neurons in limbic structures (bed nucleus of the stria terminalis [BNST] and central nucleus of the amygdala [CNA]), the dorsal raphe (DR), and Barrington's nucleus (BN); comparisons were made to the PVN. In all of these areas, nicotine activated CRH neurons in a dose-dependent manner, showing differential sensitivity and efficacy with respect to region. CNA CRH neurons were most responsive and were maximally stimulated by the low dose of nicotine (62% of CRH neurons were cFos+, compared to 10-27% of the CRH population in other regions, including the PVN). Although the BNST also was activated by the low dose, only the non-CRH+ neurons were involved; in contrast, 41% of the BNST CRH neurons responded to the higher dose. Nicotinic activation of DR neurons was dose-dependent, with 22% of the CRH neurons activated by the high dose. Few BN neurons were activated by the low dose of nicotine, but 26% of the CRH population responded to the higher dose. These results indicate that the effect(s) of nicotine on the brain may be mediated, in part, by the selective activation of specific extrahypothalamic regions containing CRH neurons that also are involved in autonomic and behavioral responses to stress. The large fraction of CRH neurons responding to the low dose of nicotine in the CNA suggests that this limbic region may be particularly important in mediating these CNS effects of nicotine.     

Active cross-protection induced by a recombinant baculovirus expressing chimeric infectious bursal disease virus structural proteins

The VP2 structural gene encoded in the large genomic segment A of the variant GLS strain of infectious bursal disease virus (IBDV) was modified to encode a neutralization epitope (B69), found only on classic strains of IBDV. A chimeric cDNA clone of the large segment A, encoding VP3, VP4, and the modified variant IBDV VP2 structural proteins, was expressed in a recombinant baculovirus. The chimeric protein expressed was assessed with a panel of neutralizing monoclonal antibodies (MAbs), and it contained not only all previously MAb-defined GLS variant strain epitopes but also the B69 neutralization epitope found on classic IBDV strains. Complete active protection was afforded to specific-pathogen-free chickens by a subunit chimeric vaccine against virulent challenge with the classic IM and STC strains, as well as against the variant E/Del and GLS IBDV strains. Compared with a previously tested recombinant subunit vaccine, which incorporated unmodified baculovirus-expressed large-segment A GLS proteins, the recombinant chimeric subunit vaccine resulted in markedly improved active cross-protection against classic IBDV challenge.     

In vivo effect of chemically induced fibrosarcoma on copper metabolism of liver in mice

The clinical and serological responses to therapy were evaluated for at least 1 year in 68 dogs with antibody titers positive for Ehrlichia canis. Treatments were of variable periods with primarily tetracycline hydorchloride and/or doxycycline. Sixteen dogs had initial titers of 1:20 and, at the end of the year, were asymptomatic, no longer receiving medication, and had negative serology. The average length of treatment with tetracycline HCl and/or doxycycline was 85 days (range, 14 to 360 days). Of 39 dogs with initial titers of 1:2,560 or greater, 1 died, 25 were asymptomatic, and 13 were lost to follow-up at the end of the study. The average length of treatment was 210 days (range, 21 to 630 days). Twenty-seven dogs were seropositive at > or = 1:2,560 when the sera was last tested. Thirteen dogs had initial titers of 1:80 to 1:1,280. Of these 13 dogs, 2 died, 2 were lost to follow-up, and 9 were asymptomatic and had titers ranging from negative to > or = 1:2,560 at the end of the study. The persistence of antibodies, prolonged subclinical phase, and delayed relapses despite long-term medication, suggest inadequate chemotherapeutic agents or may be natural features of latency of ehrlichiosis in dogs.