P-glycoprotein is involved with the removal of drugs, most of them cations, from the plasma membrane and cytoplasm. Pgp is also associated with movement of ATP, an anion, from the cytoplasm to the extracellular space. The central question of this study is whether drug and ATP transport associated with the expression of Pgp are in any way coupled. We have measured the stoichiometry of transport coupling between drug and ATP release. The drug and ATP transport that is inhibitable by the sulfonylurea compound, glyburide (P. E. Golstein, A. Boom, J. van Geffel, P. Jacobs, B. Masereel, and R. Beauwens, Pfluger's Arch. 437, 652, 1999), permits determination of the transport coupling ratio, which is close to 1:1. In view of this result, we asked whether ATP interacts directly with Pgp substrates. We show by measuring the movement of Pgp substrates in electric fields that ATP and drug movement are coupled. The results are compatible with the view that substrates for Pgp efflux are driven by the movement of ATP through electrostatic interaction and effective ATP-drug complex formation with net anionic character. This mechanism not only pertains to drug efflux from tumor cells overexpressing Pgp, but also provides a framework for understanding the role of erythrocytes in drug resistance. The erythrocyte consists of a membrane surrounding a millimolar pool of ATP. Mammalian RBCs have no nucleus or DNA drug/toxin targets. From the perspective of drug/ATP complex formation, the RBC serves as an important electrochemical sink for toxins. The presence in the erythrocyte membrane of approximately 100 Pgp copies per RBC provides a mechanism for eventual toxin clearance. The RBC transport of toxins permits their removal from sensitive structures and ultimate clearance from the organism via the liver and/or kidneys.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMedDate not supplied

Ductal anatomy: a determinant of successful stenting in hypoplastic left heart syndrome.

Interventional palliation for hypoplastic left heart syndrome (HLHS) could reduce the current morbidity and mortality. Stenting of the arterial duct is the critical interventional step for HLHS. We reviewed our experience with 40 consecutive patients with HLHS referred for stenting of the ductus arterious (DA). Thirty-nine of 40 (97%) infants had suitable anatomy and were successfully stented. The infants were grouped by orientation of the ductus in the frontal plane. Type 1 DA anatomy had a leftward loop at a mean orientation of 18 degrees from the vertical plane. Type 2 ductal anatomy was mesoverted, with a mean orientation of 7.1 degrees from the vertical plane. Type 3 ductal anatomy displayed a rightward axis, with a mean of -4 degrees rightward. Orientation of the DA was significantly related to length of the ductus, number of stents required for complete coverage, and technical and procedural complications. Type 1 DA occurred in 65% of patients, and there was 100% technical success, no mortality, and only an 8% incidence of complications. Type 2 anatomy occurred in 27% of patients and there was 100% success. However, the technical and procedural complications increased to approximately 50%. Type 3 ductal anatomy was seen in only 3 patients, 2 of whom were successfully stented. There was no procedural-related mortality, and all stented patients were weaned from prostaglandin. There were only two late complications (coarctation). We conclude that ductal stenting using self-expanding nitinol stents is successful in more than 95% of infants with HLHS. Patients with HLHS and favorable ductal anatomy should be considered for primary ductal stenting.

Blood Vessel Prosthesis Implantation↗

PubMedDate not supplied

Isolated innominate artery in 22q11 microdeletion.

A patient with an isolated left innominate artery (with a right-sided cervical aortic arch) is described. This is the first report of such an anomaly associated with chromosome 22q11 microdeletion. The abnormality represents an interruption in the primitive aortic arch that is atypical for this chromosome deletion.

Brachiocephalic Trunk↗

PubMedDate not supplied

Neurochemical and neurobehavioral effects of neonatal administration of beta-N-methylamino-L-alanine and 3,3'-iminodipropionitrile.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that is characterized by a loss of motor neurons in the spinal cord, brain stem, and cortex. The present study examined the neurochemical and neurobehavioral consequences of the neonatal administration of IDPN and BMAA, two neurotoxins previously considered as experimental models of ALS. Sprague-Dawley rat pups (male and female) were injected SC with IDPN or BMAA. The following treatment groups (n = 5-14 per group) were studied; IDPN [100 mg/kg on postnatal days (PNDs) 2, 4, and 6], BMAA-A (500 mg/kg PND 5 only), BMAA-B (500 mg/kg PND 2 and 5), and BMAA-C (100 mg/kg PND 2 and 5). Neurobehavioral testing was performed and the rats were sacrificed at 101 days of age. Monoamine and amino acid content was measured by HPLC in brain regions and the spinal cord. IDPN treatment impaired the righting reflex and decreased forepaw suspension times. BMAA-A and BMAA-B males exhibited an increase in open field behavior. The hindlimb splay of BMAA-A females was increased. Other significant behavioral and endocrine effects were also seen with neonatal IDPN or BMAA treatment. IDPN females had increased spinal cord content of norepinephrine (NE), serotonin, and 5-hydroxyindoleacetic acid (5-HIAA). IDPN males had no alterations in spinal cord content of NE or Glu, but serotonin and 5-HIAA content were increased. BMAA-A and BMAA-B males also had elevated spinal cord 5-HIAA content whereas females were unaffected. Glu and Asp content in the spinal cord was elevated in the female BMAA-C group. Monoamines were also altered in the cerebellum, mediobasal hypothalamus, and hippocampus by IDPN and BMAA treatment. alpha 2-Adrenergic binding sites were increased in the spinal cord by IDPN and in the cerebellum by BMAA treatment. The results of this study clearly demonstrated that both IDPN and BMAA given neonatally can produce changes in motor function and spinal cord neurochemistry, although the pattern of the effects is both treatment and sex dependent. Neonatal exposure to either IDPN or BMAA resulted in permanent changes in adult neurochemistry that may be related to reorganizational effects induced by toxin-mediated neuroplasticity in developing neurons.

Amino Acids↗

PubMedDate not supplied

Microleakage of seven dentin bonding agents.

The purpose of this study was to evaluate the ability of seven dentin bonding agents to reduce dye penetration at the margins of microfill composite restorations in dentinal cavities. Forty extracted molars were selected and cleaned. Cavity preparations were made in dentin with #55 carbide burs. The preparations were restored with Silux after application of one of the following dentin bonding agents: Gluma, Scotchbond 2, Tenure, Prisma Universal Bond 2, Mirage-Bond, XR Bond, and All-Bond. Samples were thermocycled for 200 cycles between 3 degrees C and 60 degrees C, then immersed in a 0.05 percent crystal violet solution for 2 hours. The samples were embedded in clear casting resin, sectioned, and examined with a light microscope. Our results indicated that the dentin bonding systems reduced, but failed to totally eliminate, microleakage around the composite resin restorations.

Adhesives↗

PubMedDate not supplied

Effect of the tenure dentin bonding system on leakage of light-activated liners.

This study investigated the effect of the Tenure dentin bonding system on the sealing properties of four light-activated liners. Dentinal slot preparations were made in extracted human molars and "restored" with Cavalite, TimeLine, VLC Dycal, and Zionomer liners. Samples were immersed in 0.05 percent crystal violet solution for 2 hours, then embedded in clear casting resin, sectioned, and examined with an optical microscope. Our results indicated that the Tenure dentin bonding system reduced dye penetration around each of the light-activated liners tested. The Tenure/VLC Dycal system provided a more effective seal than the other liners.

Acid Etching, Dental↗

PubMedDate not supplied

Effect of varnishes on surface microhardness of basing materials.

This study investigated the surface microhardness of five basing materials with four varnishes applied to them. Ten Plexiglass molds with 7-mm diameter holes were prepared. Basing materials of Cavitec, Life, Ketac Bond, TimeLine, and Cavalite were placed in the molds to produce 20 samples each. Copalite, Universal, Contact, and Barrier varnishes were applied to the top and bottom surfaces of the base material samples at 1 hour and 24 hours. After air drying, the surface microhardness of the samples was tested with a Micromet II microhardness tester. The surface microhardness of all the basing materials tested was reduced when varnishes were applied to them. Contact and Barrier reduced surface microhardness value more than Copalite and Universal.

Acrylic Resins↗

PubMedDate not supplied

Microleakage between composite resin and basing materials.

This study investigated the microleakage between a composite resin restorative material and six basing materials. Cavities were prepared in polymerized composite resin samples and "restored" with Cavitec, Life, Ketac-Bond, BaseLine, Cavalite, and VLC Dycal. The samples were thermocycled and immersed in 0.05 percent crystal violet solution for 2 hours, then embedded in clear casting resin, sectioned and examined with an optical microscope. Our results indicated that Cavalite and VLC Dycal allowed no dye penetration. Cavitec and Life had a moderate degree of dye penetration and Ketac-Bond and BaseLine had a relatively high degree of penetration.

Acrylic Resins↗

PubMedDate not supplied

Microleakage between glass-ionomer cement and composite resins.

This study investigated the microleakage between glass-ionomer cement and Silux or Herculite with and without Scotchbond 2. Cavities were prepared in polymerized composite resin samples and "restored" with a glass ionomer cement with and without Scotchbond 2. The samples were thermocycled and immersed in 0.05% crystal violet solution for 2 hours, then embedded in clear casting resin, sectioned, and examined with an optical microscope. The results indicated that a high degree of dye penetration was found in samples of GC and Silux, and GC and Herculite without Scotchbond 2. The use of Scotchbond 2 significantly reduced the degree of dye penetration, but did not completely eliminate dye penetration.

Analysis of Variance↗

PubMedDate not supplied

Relationship between dental amalgam mercury content and emission.

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Air↗