Effects of Chronic Renal Failure on Brain Drug Transporters in Rats

ABSTRACT: Studies demonstrated that chronic renal failure (CRF) affects the expression and activity of intestinal, hepatic, and renal drug transporters. Such drug transporters are expressed in brain cells and at the blood-brain barrier (BBB), where they limit the entry and distribution of drugs in the brain. Perturbations in brain drug transporter equilibrium by CRF could lead to central drug toxicity. This study evaluates how CRF affects BBB drug transporters using a 5/6 nephrectomized rat model. Protein and mRNA expression of influx transporters [organic anion-transporting polypeptide (Oatp), organic anion transporter (Oat)] and efflux transporters [P-glycoprotein (P-gp), multidrug resistance-related protein (Mrp), breast cancer resistance protein (Bcrp)] were measured in CRF and control rat brain. Intracerebral accumulation of radiolabeled benzylpenicillin, digoxin, doxorubicin, and verapamil was used to evaluate BBB drug permeability. Protein expression of the transporters was evaluated in rat brain endothelial cells (RBECs) and astrocytes incubated with control and CRF rat serum. We demonstrated significant decreases (30-50%) in protein and mRNA levels of Bcrp, Mrp2 to -4, Oat3, Oatp2 and -3, and P-gp in CRF rat brain biopsies, as well as in astrocytes and RBECs incubated with CRF serum. These decreases did not correlate with in vivo changes because BBB permeability of benzylpenicillin was decreased by 30% in CRF rats, whereas digoxin, doxorubicin, and verapamil permeabilities were unchanged. It thus seems that even with decreased drug transporters, BBB integrity and function is conserved in CRF

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In Search of the Confucian Family

This article presents findings from interviews with 16 middle school students and their parents in Guangzhou, China, about parent-adolescent relationships. Themes revealed from the conversations suggested that adolescents were generally pleased with the good relationships with their parents, that they enjoyed the respect their parents had for them as their parents tended to use peaceful reasoning to communicate parental expectations, and that they themselves cared a lot about academic attainment because it would lead to good jobs in the future. In addition, working-class parents expressed a sense of inadequacy while holding on to the high hopes and expectations for their children, whereas middle-class parents and parents who had middle-class experiences either in their occupation or in their education tried to raise well-rounded children apart from emphasis on academic achievement. In sum, these parents and adolescents represented a generation that was influenced by a myriad of social forces in modern China, including Confucianism, Socialism, and Capitalism, instead of simply and solely by classical Confucianism. In other words, Confucianism, along with the lifestyle that supported it, was far less salient than assumed in a lot of research on Chinese families and parent-child relationships