Daily sc injection of gentamicin(100 mg/kg)for 4 days produced a significant decrease in the activities of renal cortical Na^+,K^+-ATPase and alkaline phosphatase.The observed reduction in renal functional enzymatic m...Daily sc injection of gentamicin(100 mg/kg)for 4 days produced a significant decrease in the activities of renal cortical Na^+,K^+-ATPase and alkaline phosphatase.The observed reduction in renal functional enzymatic markers was associated with significant elevation in sphingomyelin, phosphatidylserine,phosphatidylglycerol,pbosphatidylinositol,phosphatidylcholine,and total phospholipid.Gentamicin significantly decreased the activity of renal phospholipase C.Nitren- dipine(25 mg/kg/day)for 7 days po for 4 days alone did not markedly alter the activities of kidney phospholipase C,alkaline phosphatase,and Na^+,K^+-ATPase or tissue phospholipid lev- els.Daily administration of nitrendipine for 3 days followed by concurrent treatment ofnitren- dipine and gentamicin failed to prevent antibiotic-induced renal histopathologic changes,phos- pholipidosis,or decrease in alkaline phosphatase.However,in rats simultaneously given nitren- dipine and gentamicin the activity of Na^+,K^+-ATPase returned to control values,indicating a selective blocking action for nitrendipine. The inability of nitrendipine to prevent gentamicin- induced renal pfiospholipidosis or decreases in enzymatic function markers was associated with significantly elevated tissue aminoglycoside levels when compared to values seen in rats given only the antibiotic.Evidence suggests that nitrendipine is not effective in lowering the concentra- tion of gentamicin in renal cortex.The effectiveness of an agent in providing protection against aminoglycoside nephrotoxicity may be associated with the ability of the drug to lower renal gentamicin content.1989 Academic Press,Inc.展开更多
The necessity for understanding normal human cognitive processes and behavior, and themechanisrns which result in dysfunction in these processes are dependant on utilization of a suitable animal model. In order to dev...The necessity for understanding normal human cognitive processes and behavior, and themechanisrns which result in dysfunction in these processes are dependant on utilization of a suitable animal model. In order to develop pharmaceutical agents to alleviate mental disturbances and enable the individual to cope within the norms of society, it is incumbent upon investigators to choose a species in which pharmacokinetic principles are established and resemble those of hurnans. The choice of rats in cognition research studies has specific advantages in that these anirnals possess similar pharrnacodynamic parameters to hurnans. Further advantages include availability, low cost, ease of breeding, maintenance and an extensive literature database which enable comparisons to present findings. However, there are substantial differences in the perforrnance of various rat strains in tasks of learning, memory, attention, and responses to stress or drugs. In addition to rat strain, quantity of thed also exerts profound consequences on animal behavior. The aim of this review is to demonstrate that there are differences in the central nervous systern responsivencess of rat strains to chemicals and these could be related to factors such as source of supplier, type and quantity of feed, or season of the year. It is also evident that the genotype differs amongst strains and this may be responsible for the observed differences in CNS sensitivity to chemicals. Strain differences must be identified and taken into consideration in interpretation of assessrnent of neurobehavioural functions. It is also incumbent upon the investigators to utilize healthy (diet-controlled) animal models.展开更多
文摘Daily sc injection of gentamicin(100 mg/kg)for 4 days produced a significant decrease in the activities of renal cortical Na^+,K^+-ATPase and alkaline phosphatase.The observed reduction in renal functional enzymatic markers was associated with significant elevation in sphingomyelin, phosphatidylserine,phosphatidylglycerol,pbosphatidylinositol,phosphatidylcholine,and total phospholipid.Gentamicin significantly decreased the activity of renal phospholipase C.Nitren- dipine(25 mg/kg/day)for 7 days po for 4 days alone did not markedly alter the activities of kidney phospholipase C,alkaline phosphatase,and Na^+,K^+-ATPase or tissue phospholipid lev- els.Daily administration of nitrendipine for 3 days followed by concurrent treatment ofnitren- dipine and gentamicin failed to prevent antibiotic-induced renal histopathologic changes,phos- pholipidosis,or decrease in alkaline phosphatase.However,in rats simultaneously given nitren- dipine and gentamicin the activity of Na^+,K^+-ATPase returned to control values,indicating a selective blocking action for nitrendipine. The inability of nitrendipine to prevent gentamicin- induced renal pfiospholipidosis or decreases in enzymatic function markers was associated with significantly elevated tissue aminoglycoside levels when compared to values seen in rats given only the antibiotic.Evidence suggests that nitrendipine is not effective in lowering the concentra- tion of gentamicin in renal cortex.The effectiveness of an agent in providing protection against aminoglycoside nephrotoxicity may be associated with the ability of the drug to lower renal gentamicin content.1989 Academic Press,Inc.
文摘The necessity for understanding normal human cognitive processes and behavior, and themechanisrns which result in dysfunction in these processes are dependant on utilization of a suitable animal model. In order to develop pharmaceutical agents to alleviate mental disturbances and enable the individual to cope within the norms of society, it is incumbent upon investigators to choose a species in which pharmacokinetic principles are established and resemble those of hurnans. The choice of rats in cognition research studies has specific advantages in that these anirnals possess similar pharrnacodynamic parameters to hurnans. Further advantages include availability, low cost, ease of breeding, maintenance and an extensive literature database which enable comparisons to present findings. However, there are substantial differences in the perforrnance of various rat strains in tasks of learning, memory, attention, and responses to stress or drugs. In addition to rat strain, quantity of thed also exerts profound consequences on animal behavior. The aim of this review is to demonstrate that there are differences in the central nervous systern responsivencess of rat strains to chemicals and these could be related to factors such as source of supplier, type and quantity of feed, or season of the year. It is also evident that the genotype differs amongst strains and this may be responsible for the observed differences in CNS sensitivity to chemicals. Strain differences must be identified and taken into consideration in interpretation of assessrnent of neurobehavioural functions. It is also incumbent upon the investigators to utilize healthy (diet-controlled) animal models.
