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  • 1
    Digitale Medien
    Digitale Medien
    Acute toxicity of cyclohexylmethylphosphonofluoridate (CMPF) in rhesus monkeys: serum biochemical and hematologic changes (1995)
    Springer
    Archives of toxicology 69 (1995), S. 379-383 
    Details
    ISSN: 1432-0738
    Schlagwort(e): Keywords Cyclohexylmethylphosphonofluoridate ; Rhesus monkey ; Serum ; Biochemistry ; Hemotology
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Changes in serum biochemical and hematological parameters were studied in 20 male rhesus monkeys following acute poisoning by the organophosphate nerve agent cyclohexylmethylphosphonofluoridate (CMPF or GF). Animals were challenged with 5×LD50 GF (233 μg/kg, IM) following pretreatment with pyridostigmine (0.3–0.7 mg/kg per 24 h) and treated with atropine (0.4 mg/kg, IM) and either 2-PAM (25.7 mg/kg, IM) or HI6 (37.8 mg/kg, IM) at the onset of clinical signs or at 1 min after exposure. Muscle fasciculations, tremors, or convulsions occurred in 19 of 20 animals. Serum biochemical and hematologic parameters were analyzed 2 days and 7 days after exposure and compared to pre-exposure baseline values. Significant increases in creatine kinase (CK), lactate dehydrogenase (LD), aspartate transaminase (AST), alanine transaminase (ALT) and potassium ion (K+), associated with damage to striated muscle and metabolic acidosis, occurred in both oxime-treated groups 2 days after exposure. Total protein, albumin, red blood cell (RBC) count, hemoglobin concentration (Hb) and hematocrit (Hct), were decreased in both oxime-treated groups at 7 days. The results demonstrate that animals exposed to a single high dose of GF and treated with standard therapy exhibit changes in serum biochemical and hematological indices directly and indirectly associated with their clinical presentations.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s002040050187
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  • 2
    Digitale Medien
    Digitale Medien
    Arteether-induced brain injury in Macaca mulatta. I. The precerebellar nuclei: the lateral reticular nuclei, paramedian reticular nuclei, and perihypoglossal nuclei (2000)
    Springer
    Anatomy and embryology 201 (2000), S. 383-397 
    Details
    ISSN: 1432-0568
    Schlagwort(e): Key words Lateral reticular nuclei ; Paramedian reticular nuclei ; Perihypoglossal nuclei ; Malaria ; Arteether ; Artemisinin ; Neurotoxicity ; Rhesus monkey ; Antimalarial drugs ; Cerebral malaria ; Macaca mulatta ; Plasmodium falciparum
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Malaria poses a threat across several continents: Eurasia (Asia and parts of Eastern Europe), Africa, Central and South America. Bradley (1991) estimates human exposure at 2,073,000,000 with infection rates at 270,000,000, illnesses at 110,000,000, and deaths at 1,000,000. Significant mortality rates are attributed to infection by the parasite Plasmodium falciparum, with an estimated 90% among African children. A worldwide effort is ongoing to chemically and pharmacologically characterize a class of artemisinin compounds that might be promising antimalarial drugs. The U.S. Army is studying the efficacy and toxicity of several artemisinin semi-synthetic compounds: arteether, artemether, artelinic acid, and artesunate. The World Health Organization and the U.S. Army selected arteether for drug development and possible use in the emergency therapy of acute, severe malaria. Male Rhesus monkeys (Macaca mulatta) were administered different daily doses of arteether, or the vehicle alone (sesame oil), for a period of either 14 days, or 7 days. Neuropathological lesions were found in 14-day arteether treated monkeys in the precerebellar nuclei of the medulla oblongata, namely: (1) the lateral reticular nuclei (subnuclei magnocellularis, parvicellularis, and subtrigeminalis), (2) the paramedian reticular nuclei (subnuclei accessorius, dorsalis, and ventralis), and the perihypoglossal nuclei (n. intercalatus of Staderini, n. of Roller, and n. prepositus hypoglossi). The data demonstrate that the simian medullary precerebellar nuclei have a high degree of vulnerability when arteether is given for 14 days at dose levels between 8 mg/kg per day and 24 mg/kg per day. The neurological consequences of this treatment regimen could profoundly impair posture, gait, and autonomic regulation, while eye movement disorders might also be anticipated.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004290050326
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  • 3
    Digitale Medien
    Digitale Medien
    Regional permeability differences between the proximal and distal portions of the isolated salmonid posterior intestine (1997)
    Springer
    Journal of comparative physiology 167 (1997), S. 370-377 
    Details
    ISSN: 1432-136X
    Schlagwort(e): Key words Proximal and distal intestine ; Mannitol flux ; Transepithelial electrical resistance ; Enhancement ; Salmon
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract The objective of this study was to assess regional variations in the permeability of the salmon posterior intestine and to evaluate the effect of permeability enhancers as a basis for oral delivery of biologically active peptides. Proximal and distal portions of the posterior intestine of the chinook salmon (Oncorhynchus tshawytscha) were removed, mounted as flat sheets in Ussing chambers and superfused with trout Ringer's. Intestinal permeability was assessed under short-circuit conditions by measurement of 14C-mannitol (mucosal to serosal) flux. Tissues were treated either with the mucolytic agent dithiothreitol (10 mmol · l−1), the permeability enhancer sodium deoxycholate (5.0 mmol · l−1) or both and compared to untreated controls. Both proximal and distal control tissues had low permeabilities, but the distal region had a lower transepithelial electrical resistance and produced significantly less mucus. Treatment with either dithiothreitol or sodium deoxycholate alone reduced mucus adhering to tissue in both regions but did not increase permeability or change transepithelial electrical resistance. In the distal region, sequential treatment with both agents significantly reduced adhering mucus, decreased transepithelial electrical resistance, and increased tissue permeability. The salmon posterior intestine can be divided into proximal and distal regions. The distal region is more likely to have the necessary permeability and responsiveness to enhancement for the successful delivery of peptides or polar drugs.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s003600050086
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  • 4
    Digitale Medien
    Digitale Medien
    Permeability of the salmon (Oncorhynchus tshawytscha) posterior intestine in vivo to two hydrophilic markers (1998)
    Springer
    Journal of comparative physiology 168 (1998), S. 562-568 
    Details
    ISSN: 1432-136X
    Schlagwort(e): Key words Mannitol ; Fluorescein ; Permeability ; Salmon ; Posterior intestine ; Enhanced epithelial permeability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract This study characterised the permeability of the salmonid posterior intestine in vivo, to two hydrophilic markers of different molecular weight, both in the presence and absence of sodium deoxycholate (SDA), and determined the influence of mucosal secretions. The posterior intestine of chinook salmon was cannulated with a balloon catheter and the lumen infused with a solution of fluorescein and 14C-mannitol. In treated fish, the solution also contained 5.0 mmol · l−1 SDA. Blood samples from the dorsal aorta were taken at regular time intervals over 3 h. Clearances and volumes of distribution were assessed by intravenous administration of the markers to another group of fish. In the absence of SDA, low permeabilities were recorded for both markers; however, permeabilities for both were significantly greater in the treated groups. Both solutes had volumes of distribution similar to values reported elsewhere. Metabolism of fluorescein by the liver resulted in its plasma clearance. In contrast, elimination of mannitol was negligible during the study period, probably due to the lowered glomerular filtration rates observed in sea water adapted fish. Compared to in vitro investigations, in vivo mucus secretions were significantly lower and solute delivery across the epithelium was higher. Results from these in vivo investigations have implications for the oral delivery of peptides to salmonids.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s003600050178
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