A central goal of The Academy of Breastfeeding Medicine is the development of clinical protocols for managing common medical problems that may impact breastfeeding success. These protocols serve only as guidelines for the care of breastfeeding mothers and infants and do not delineate an exclusive course of treatment or serve as standards of medical care. Variations in treatment may be appropriate according to the needs of an individual patient.

The transport systems involved in the export of cellular reduced glutathione (GSH) have not been identified, although recent studies implicate a role for some of the multidrug resistance associated proteins (MRP), including MRP1 and MRP2. The present study examined the hypothesis that the yeast orthologue of MRP, Ycf1p, mediates ATP-dependent GSH transport. [3 H]GSH transport was measured in vacuolar membrane vesicles isolated from a control strain of Saccharomyces cerevisiae (DTY165), the isogenic DTY167 strain that lacks a functional Ycf1p, and in DTY167 transformed with a 2-m plasmid vector containing YCF1. GSH transport in control vacuolar membrane vesicles was mediated largely by an ATP-dependent, low affinity pathway (K m ‫؍‬ 15 ؎ 4 mM). ATP-dependent [ 3 H]GSH transport was cis-inhibited by substrates of the yeast Ycf1p transporter and inhibited by 4,4-diisothiocyanatostilbene-2,2-disulfonic acid, probenecid, and sulfinpyrazone, inhibitors of MRP1 and MRP2, but was minimally affected by membrane potential or pH gradient uncouplers. In contrast, ATP-dependent GSH transport was not seen in vacuolar membrane vesicles isolated from the DTY167 yeast strain without a functional Ycf1p but was restored to near wild-type levels in the DTY167 strain transformed with YCF1 and expressing the vacuolar Ycf1p transporter. On the other hand, expression and functional activity of a bile acid transporter, Bat1p, and of the V-type ATPase were similar in all three yeast strains. These results provide direct evidence for ATP-dependent low affinity transport of GSH by the yeast Ycf1p transporter. Because of the structural and functional homology between Ycf1p and MRP1 and MRP2, these data support the hypothesis that GSH efflux from mammalian cells is mediated by these membrane proteins.Turnover of cellular GSH is initiated by export across the plasma membrane for delivery to the catabolic ectoenzymes ␥-glutamyl transpeptidase and dipeptidase (1, 2). Intracellular GSH concentrations are normally 1-10 mM, whereas blood plasma concentrations are 1-20 M. The mechanisms of GSH transport are not well understood, although recent studies provide some insight (3-7). One mechanism of GSH release involves the organic anion-transporting polypeptide, Oatp1 (5). Li and co-workers (5) recently demonstrated that Oatp1 functions as a GSH/organic solute exchanger. Cellular release of GSH down its large electrochemical gradient apparently energizes uptake of organic solutes via the Oatp1 transporter. Oatp1 is a member of a growing family of organic solute transporters whose driving force has not been identified, although the work of Li et al. (5) suggests that GSH exchange may be both a common mechanism of energy coupling and a mechanism of GSH release from cells.An additional mechanism of GSH release may involve the MRP 1 family of membrane transporters (6). Studies in intact cells indicate that GSH is released by ATP-dependent mechanisms, including possibly the MRP1 and MRP2 proteins; however, none of these studies have directly documented AT...

is the development of clinical protocols for managing common medical problems that may impact breastfeeding success. These protocols serve only as guidelines for the care of breastfeeding mothers and infants and do not delineate an exclusive course of treatment or serve as standards of medical care. Variations in treatment may be appropriate according to the needs of an individual patient. Definitions used in this protocol Exclusive breastfeeding: Feeding only breast milk (at the breast or own mothers' expressed breast milk), no food or water except vitamins, minerals and medications. Supplementary feedings: Additional fluids provided to a breastfed infant before 6 months (recommended duration of exclusive breastfeeding). These fluids may include donor human milk, infant formula or other breast milk substitutes (eg. glucose water). Complementary feedings: Solid or semi-solid foods provided to an infant in addition to breastfeeding when breast milk alone is no longer sufficient to meet nutritional needs. Term infant: In this protocol 'term infant' also includes early term infants (gestational age 37-38 6/7 weeks). BackgroundGiven early opportunities to breastfeed, breastfeeding assistance, and instruction the vast majority of mothers and infants will successfully establish breastfeeding. Although some infants may not successfully latch and feed well during the first day (24 hours), most will successfully breastfeed with time, appropriate evaluation and

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