Drugs online research references
psych.ufl.edu
The capacity of aging rats to defend body fluid homeostasis in response to a variety of dipsogenic and natriorexigenic stimuli was assessed. Male and female rats of both the Fischer 344 (FR) and Sprague-Dawley (SD) strains were used and tested at target ages of approximately 5, 10, 15, and 20 mo in both longitudinal and cross-sectional studies. There were no consistent age-related declines in water intake in response to water deprivation or acute administration of hypertonic NaCl; angiotensin (ANG) I, II, III; or isoproterenol. Likewise, there were no major impairments in either urinary excretion of the hypertonic NaCl load or excretion of water or hypotonic NaCl loads, although the latter were excreted more slowly in the older cohorts. The preference/aversion functions for NaCl solutions differed between SD and FR rats, but did not change with age except in male FR rats that lost their aversion to dilute NaCl at 20 mo of age. Intake of hypotonic NaCl solution after acute sodium depletion (furosemide treatment) showed a partial decline with age, and the older rats sustained larger estimated sodium deficits after a 6-h repletion period. A more complete age-related decline was observed in the intake of hypertonic NaCl stimulated by chronic dietary administration of a kininase II inhibitor (ramipril). Male rats of 15-20 mo of age showed no ramipril-induced sodium appetite. Brain ANG II receptor density, determined by autoradiography, declined by almost 50% in the paraventricular nucleus at 20 mo of age and declined slightly in the organum vasculosum laminae terminalis but did not decline in either the supraoptic nucleus or subfornical organ. Thus the major deficits in fluid intake in aging rats are related to salt appetite; the mechanism was not identified definitively.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9362310&dopt=Abstract
J Pharmacol Exp Ther. 1998 Jan;284(1):111-5.
Pharmacokinetics of IgG and IgM anti-ganglioside antibodies in rats and monkeys after intrathecal administration.
Bergman I, Burckart GJ, Pohl CR, Venkataramanan R, Barmada MA, Griffin JA, Cheung NK.
Department of Pediatrics, University of Pittsburgh, Pennsylvania, USA.
Intrathecal (i.t.) administration of monoclonal antibodies (mAbs) represents a new therapeutic approach for the treatment of leptomeningeal cancer, which is rapidly fatal. This study describes the pharmacokinetics of intrathecally administered mAbs in rats and monkeys to optimize their use for regional antineoplastic therapy. We hypothesized that mAbs, which are high-molecular-weight, polar compounds, would be eliminated from the cerebrospinal fluid (CSF) at the same rate as bulk flow of CSF. We found that an IgM mAb was cleared from rat CSF at the rate of CSF bulk flow (0.0041 ml/min), but an IgG mAb was cleared at a faster rate (0.011 ml/min). We attempted to reduce the CSF clearance of an IgG mAb by administration of acetazolamide and furosemide, which inhibit the rate of CSF production and CSF bulk flow. We demonstrated that the administration of acetazolamide and furosemide reduced the clearance of IgG mAb from rat CSF by 58%. These results establish that bulk flow of CSF determines a minimum rate of elimination from the CSF for IgM mAbs and that additional mechanisms operate to clear IgG mAbs from the CSF. Inhibition of CSF production by acetazolamide and furosemide increased the area under the CSF concentration vs. time curve of IgG mAbs in the CSF. The increased area under the CSF concentration vs. time curve is likely to improve the therapeutic index of these agents for i.t. therapy.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9435168&dopt=Abstract
Gen Pharmacol. 1998 Feb;30(2):213-20.
Structural requirements and ionic mechanism of the Mytilus inhibitory peptides (MIPs) on Helix central neurons.
Pedder SM, Chen ML, Muneoka Y, Walker RJ.
Department of Physiology & Pharmacology, School of Biological Sciences, University of Southampton, UK.
1. The structural and ionic requirements for potent FVamide-induced inhibition were investigated using Helix aspersa central neurons under current or voltage clamp. 2. For potent FVamide inhibition the full hexapeptide sequence, GSPYFVamide, was required. The rank order of decreasing potency was GSPYFVamide >> SPYFVamide> PYFVamide > YFVamide. 3. GSPYFVamide inhibition involved an increase in conductance to both potassium and chloride ions as demonstrated by ion substitution experiments and addition of 4-aminopyridine, tetraethylammonium, 4,4-di-isothiocyanatostilbene-2,2'-disulfonic acid, 4,4-dinitrostilbene-2,2'-disulfonic acid disodium salt and furosemide to the solution bathing the preparation.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9502176&dopt=Abstract
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