ABSTRACT
Recombinant-inbred CXBK mice have been used for various studies as putative mu-opioid-receptor deficient mice. However, CXBK mice have never been compared with gene-targeting mice lacking the mu-opioid receptor (muKO) and the K-opioid receptor (kappaKO). Here we report that CXBK mice show distinct behavioural phenotype in opioid-induced analgesia and sedation. Intraperitoneal (i.p.) administration of morphine (3 and 10 mg kg(-1)) induced significantly lower levels of analgesia in CXBK mice than in the control C57BL/6 mice, while higher doses of morphine (30 and 100 mg kg(-1)) induced marked analgesia in CXBK mice. CXBK mice also showed lower analgesia and sedation levels than did C57 mice after i.p. administration of U-50488 (10 and 30 mg kg(-1)). The partial deficiency of sensitivity to morphine and U-50488 of CXBK mice is in sharp contrast to the complete lack of sensitivity to morphine and U-50488 in muKO and kappaKO mice, respectively. Furthermore, CXBK mice showed a lower threshold for nociceptive stimuli when they were not given an opioid, suggesting that CXBK mice could have alterations in the genes related to the nociceptive threshold. These unique behavioural phenotypes of CXBK mice suggest unique genetic alterations in CXBK mice.
Subject(s)
Behavior, Animal/drug effects , 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer/pharmacology , Analgesics, Non-Narcotic/pharmacology , Analgesics, Opioid/pharmacology , Animals , Dose-Response Relationship, Drug , Female , Hot Temperature/adverse effects , Male , Mice , Mice, Inbred C57BL , Mice, Inbred Strains , Morphine/pharmacology , Pain/etiology , Pain Threshold , Phenotype , Receptors, Opioid, kappa/agonists , Receptors, Opioid, kappa/genetics , Receptors, Opioid, mu/agonists , Receptors, Opioid, mu/genetics , Recombination, Genetic , Sensitivity and Specificity , Species SpecificityABSTRACT
The mechanism of action of antimicrobial naphthoquinones from the fungus Fusarium was studied by using Pseudomonas aeruginosa. Bostricoidin, methyl ether fusarubin, and fusarubin stimulated the oxygen consumption of bacterial cells and induced cyanide-insensitive oxygen consumption. These activities of the tested compounds were also observed in bacterial membrane preparations in a dose-dependent manner. Naphthoquinones stimulated the generation of superoxide anion and hydrogen peroxide. The naphthoquinone effectively acted as the electron acceptors for bacterial diaphorase, which could explain the antibacterial activity of Fusarium naphthoquinones since electron acceptors lead to the stimulation of respiratory activity and the generation of oxygen radical species.
Subject(s)
Anti-Infective Agents/pharmacology , Fusarium/chemistry , Naphthoquinones/pharmacology , Oxygen Consumption/drug effects , Pseudomonas aeruginosa/drug effects , Superoxides/metabolism , Anti-Bacterial Agents , Hydrogen Peroxide/metabolism , NAD/metabolism , Pseudomonas aeruginosa/metabolismABSTRACT
The antimicrobial mechanism of totarol was studied using Pseudomonas aeruginosa IFO 3080. This diterpene inhibited oxygen consumption and respiratory-driven proton translocation in whole cells, and oxidation of NADH in membrane preparation. NADH-cytochrome c reductase was inhibited by totarol while cytochrome c oxidase was not. NADH-DPIP reductase and NADH-CoQ reductase were also inhibited. The site of respiratory inhibition of totarol was thought to be near CoQ in the bacterial electron transport chain.
Subject(s)
Anti-Bacterial Agents/pharmacology , Diterpenes/pharmacology , NADH, NADPH Oxidoreductases/metabolism , Plant Extracts , Pseudomonas aeruginosa/drug effects , Abietanes , Cell Membrane/metabolism , Electron Transport/drug effects , Electron Transport Complex I , Electron Transport Complex IV/metabolism , Escherichia coli/drug effects , Microbial Sensitivity Tests , NAD/metabolism , NADH Dehydrogenase/antagonists & inhibitors , NADH, NADPH Oxidoreductases/antagonists & inhibitors , Oxygen Consumption/drug effects , Plant Roots , Pseudomonas aeruginosa/metabolism , Staphylococcus aureus/drug effectsSubject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hemolysis/drug effects , Hyperbilirubinemia/chemically induced , Leukemia, Lymphoid/drug therapy , Lymphoma/drug therapy , Vinblastine/analogs & derivatives , Vincristine/adverse effects , Adolescent , Adult , Female , Humans , Leukemia, Lymphoid/blood , Lymphoma/blood , Male , Middle Aged , Vinblastine/adverse effects , VindesineSubject(s)
Aminoglycosides/toxicity , Nephritis, Interstitial/chemically induced , Animals , Male , Rats , Rats, Inbred StrainsABSTRACT
N-acetyl-beta-D-glucosaminidase (NAG) activity in urine was measured as an indicator for detecting the onset of renal damage in patients receiving aminoglycoside and cephalosporin drugs. The studies reveal that gentamicin appears to be most nephrotoxic of the aminoglycoside antibiotics. Polyuria, not oliguria, is the first clinical symptom observed in patients with marked elevation of urinary NAG activity more than 10 mM/hr/day and moderate proteinuria and disturbance of renal function are followed in some cases. Although immediate recovery from these nephrotoxic effects of aminoglycosides and the elevation of urinary NAG activity occurs on prompt withdrawal of the drugs, two autopsied cases receiving prolonged administration of gentamicin, followed marked NAG elevation, show necrosis and exfoliation of tubular epithelial cells with little glomerular injury. The other aminoglycosides, such as amikacin, tobramycin and dibekacin are less nephrotoxic, and the administration of cephalosporin developed no nephrotoxic symptoms nor marked elevation of urinary NAG activity. The results indicate that measurement of urinary NAG activity is useful for the early diagnosis and monitoring of nephrotoxic reactions due to aminoglycosides.