The role of vasopressin as an antipyretic in the ventral septal area and its possible involvement in convulsive disorders

Perfusion of the peptide, arginine vasopressin (AVP), within the ventral septal area (VSA) of the brain of a number of species reduces fever but not normal body temperature. This antipyretic response appears to be mediated by AVP receptors of the V₁ subtype. Lesions of the VSA with kainic acid are associated with prolonged and enhanced fevers in rats. A role for endogenous AVP in fever suppression within the VSA comes from several types of experiments: (1) AVP release within the VSA is inversely correlated to fever height, (2) AVP antagonists or antiserum injected into the VSA prolong fever, (3) animals lacking endogenous AVP in the VSA (Brattleboro rat, long-term castrated rat) develop enhanced fevers. Electrical stimulation of the AVP-containing cell bodies of the bed nucleus of the stria terminalis (BST) orthodromically inhibits VSA neurons and also suppresses fever, the latter effect can be abolished with application of a V₁ antagonist to the VSA. lontophoretic studies indicate that AVP inhibits glutamatestimulated activity of thermoresponsive and other VSA neurons. AVP can also act in the VSA to cause severe motor disturbances, this action is receptor mediated and increases in severity upon sequential exposure to AVP. Because sites of action of the antipyretic and convulsive action of AVP are similar, and because animals lacking brain AVP display reduced convulsive activity, it is possible that AVP, released during fever, could be involved in the genesis of convulsive activity.     

Induced changes in intracranial pressure in the anesthetized rat and rabbit

Intracranial pressure (ICP) was measured continuously in anesthetized, free-breathing, adult, male Sprague-Dawley rats and New Zealand White rabbits by means of a subarachnoid screw technique. The effect upon ICP of changing the volumes within the cranium by infusion of artificial cerebrospinal fluid into the lateral cerebral ventricle at various rates was examined. Results obtained demonstrated some of the elastic and compensatory aspects of cerebrospinal fluid dynamics. The effects upon ICP of the intravenous administration of urea, mannitol, acetazolamide, dimethyl sulfoxide, norepinephrine, epinephrine, isoproterenol, nitroglycerin, papaverine, histamine, angiotension II, pitressin, sodium nitroprusside, diazoxide, lidocaine, sodium pentobarbitone, as well as inhalation of amyl nitrate and carbon dioxide were examined in anesthetized rats. The effect upon ICP of the intravenous infusion of urea, as well as the bolus intravenous administration of epinephrine and pitressin was examined in the anesthetized rabbit. Results obtained from these animals demonstrate the action of these experimental interventions upon ICP as measured by means of the subarachnoid screw technique.     

Use of lectins to detect and differentiate subtypes of Marek's disease virus and turkey herpesvirus glycoproteins in tissue culture

Biotinylated lectins in conjunction with an avidin-biotin-peroxidase complex were used for the first time to reveal glycoproteins in chicken and duck embryo fibroblasts infected with three prototype members of the avian herpesvirus group, Marek's disease virus serotypes 1 and 2 and turkey herpesvirus. By using a panel of 10 lectins, a pattern of reactivity emerged which was both group- and type-specific. Morphological details of the lectin-stained cells include cytoplasmic granulation, capping and bleb-like protrusions of the cell membrane. Although no antibody is necessary for the reaction, this novel approach allows specific detection of the glycan moieties of viral glycoproteins as they are synthesized during infection.     

A twelve-month study of West Nile virus antibodies in a resident and a migrant species of kestrels in Israel

Two species of kestrel, the common and lesser, were caught each month at three geographically defined locations in Israel over a 12-month period, and a total of 306 blood samples were examined for West Nile virus neutralizing antibodies. The prevalences and mean antibody titers were analyzed statistically by the multiple linear regression model and were shown to be significantly affected by two of the independent variables, location and age of the bird. The season had no overall effect on prevalence and titer but a comparison of the mean monthly titers revealed that April was highest and July and August the lowest statistically for the common kestrel which is a resident species. In contrast, the migrating lesser kestrel was caught only in the spring months and principally at the Jerusalem location, where eight out of 29 birds were seropositive. By comparing the serology of the non-migrating, common kestrel with the migrating, lesser kestrel, the effect of seasonality was evaluated in relation to their ecological patterns and yielded evidence for the entry in April of a small number of previously infected common kestrels into Israel. This serological approach based on continuous sampling over an extended period could be used to forecast in the coming years the timing and dispersion of West Nile virus in both Old and New Worlds if surveys are based on a limited number of informative (flag) species.     

Elevated DT-diaphorase activity and messenger RNA content in human non-small cell lung carcinoma: relationship to the response of lung tumor xenografts to mitomycin C?.

The enzyme DT-diaphorase (DTD; NAD(P)H:quinone oxidoreductase, EC 1.6.99.2), is an obligate two electron reductase which catalyzes reduction of a broad range of substrates, including quinones. We report here variations in DTD concentrations among different classes of lung tumors known also to vary in their responsiveness to cytotoxic agents. Small cell lung carcinomas (SCLCs) and cell lines derived from them have the low DTD activities and mRNA content characteristic of normal human lung, whereas non-small cell lung carcinomas (NSCLCs) have greatly elevated levels. DTD activity was increased up to 80-fold in NSCLC tumors relative to normal lung and 20-35-fold in NSCLC relative to SCLC cell lines. Increased DTD activity appeared to be a function of the NSCLC phenotype rather than a result of derivation from a cell type rich in DTD, since all histological classes of NSCLC showed this phenotype. In addition, where transfection of SCLC cell lines with the v-Ha-ras protooncogene caused a transition to a NSCLC phenotype, DTD activity was also elevated. Neuroendocrine-positive cells (SCLC, carcinoids, and a few NSCLC lines) typically had far lower DTD activities than did cell lines which lacked neuroendocrine markers (most NSCLC cells and mesotheliomas). High DTD activity may be exploited in the design of drugs which undergo bioreductive activation by this enzyme. Consistent with this, xenografts derived from NSCLC cell lines with high DTD that were grown in athymic nude mice were more susceptible to the antitumor quinone, mitomycin C, than were xenografts derived from SCLC cells containing low DTD. These data provide a mechanistic basis for the rational design of more effective bioreductive antitumor agents for use against NSCLC.     

Review: Putative mutagens and carcinogens in foods III. Butylated hydroxytoluene (BHT)

Although the average American's daily consumption of BHT can be measured in milligrams, there are numerous reports that BHT causes organ damage in laboratory animals. Only a few genotoxic effects of BHT have been reported, however, including mutagenicity in the abnormal sperm assay and ambiguous results regarding its teratogenicity. More dramatic are the modulatory effects of BHT on the actions of established mutagens and carcinogens. BHT can either enhance or inhibit mutagenic potency, depending on the substance tested. For example, in the Ames test, BHT is antimutagenic towards benzo(a)pyrene, but increases the number of Salmonella revenants induced by aflatoxin B₁. BHT is one of the few compounds to have both tumor prophylactic and tumor promoting capacities. It is the temporal sequence in which BHT and carcinogens are administered to test animals which determines how BHT affects the response to these carcinogens. In common with other antioxidants, BHT inhibits the ability of carcinogens to induce tumors in various rodent organs when the animal is given BHT prior to carcinogen treatment. Unlike other antioxidants, however, the number of tumors increase when BHT is administered after carcinogen exposure. The comutagenic and cocarcinogenic properties of BHT have been demonstrated in tests ranging from the Ames test to cell transformation procedures to in vivo assays. These effects are probably mediated by metabolites of BHT, rather than by BHT itself.