Comparison of diamond-like carbon-coated nitinol stents with or without polyethylene glycol grafting and uncoated nitinol stents in a canine iliac artery model.

OBJECTIVE: Neointimal hyperplasia is a major complication of endovascular stent placement with consequent in-stent restenosis or occlusion. Improvements in the biocompatibility of stent designs could reduce stent-associated thrombosis and in-stent restenosis. We hypothesised that the use of a diamond-like carbon (DLC)-coated nitinol stent or a polyethylene glycol (PEG)-DLC-coated nitinol stent could reduce the formation of neointimal hyperplasia, thereby improving stent patency with improved biocompatibility. METHODS: A total of 24 stents were implanted, under general anaesthesia, into the iliac arteries of six dogs (four stents in each dog) using the carotid artery approach. The experimental study dogs were divided into three groups: the uncoated nitinol stent group (n = 8), the DLC-nitinol stent group (n = 8) and the PEG-DLC-nitinol stent group (n = 8). RESULTS: The mean percentage of neointimal hyperplasia was significantly less in the DLC-nitinol stent group (26.7±7.6%) than in the nitinol stent group (40.0±20.3%) (p = 0.021). However, the mean percentage of neointimal hyperplasia was significantly greater in the PEG-DLC-nitinol stent group (58.7±24.7%) than in the nitinol stent group (40.0±20.3%) (p = 0.01). CONCLUSION: Our findings indicate that DLC-coated nitinol stents might induce less neointimal hyperplasia than conventional nitinol stents following implantation in a canine iliac artery model; however, the DLC-coated nitinol stent surface when reformed with PEG induces more neointimal hyperplasia than either a conventional or DLC-coated nitinol stent.

Hemocompatibility of surface-modified, silicon-incorporated, diamond-like carbon films.

The hemocompatibility of plasma-treated, silicon-incorporated, diamond-like carbon (Si-DLC) films was investigated. Si-DLC films with a Si concentration of 2at.% were prepared on Si (100) or Nitinol substrates using a capacitively coupled radiofrequency plasma-assisted chemical vapor deposition method using a mixed gas of benzene (C(6)H(6)) and diluted silane (SiH(4):H(2)=10:90). The Si-DLC films were then treated with O(2), CF(4) or N(2) glow discharge for surface modification. The plasma treatment revealed an intimate relationship between the polar component of the surface energy and its hemocompatibility. All in vitro characterizations, i.e. protein absorption behavior, activated partial thromboplastin time measurement and platelet adhesion behavior, showed improved hemocompatibility of the N(2-)- or O(2)-plasma-treated surfaces where the polar component of the surface energy was significantly increased. Si-O or Si-N surface bonds played an important role in improving hemocompatibility, as observed in a model experiment. These results support the importance of a negatively charged polar component of the surface in inhibiting fibrinogen adsorption and platelet adhesion.

Correlates of HIV risk in a random sample of street youths in San Francisco.

In a random sample of 203 street youths recruited in the Haight-Ashbury neighborhood of San Francisco, the authors found significant differences between those who reported that they could go home if they wanted to compared to those who perceived that they could not go back home. Those who could not go home were significantly more likely to report having been away from home for more than 3 years, having run away before age 13, having been kicked out of their home, and not being in touch with their parents compared to the other group. Those who could not go home reported significantly more-injection drug use, which puts them at high risk for HIV. Health care providers can identify street youths at highest risk by asking the question "Could you go back home today if you wanted to do so?"

Cloning and expression of the ccpA gene encoding catabolite control protein from Thermoactinomyces sp. E79.

The gene ccpA encoding the catabolite control protein A (CcpA) of Thermoactinomyces sp. E79 has been cloned and characterized. Nucleotide sequence analysis of the CcpA clone showed that the cloned fragment contained the full structural gene for a protein of 346 amino acids. The predicted amino acid sequence shows similarity to the transcriptional regulators of the Lacl-GalR family; a highly conserved helix-turn-helix motif, which might bind to DNA, was identified through comparison with regulator proteins in this family. The highest sequence identity was obtained when it was compared with the CcpA of Bacillus subtilis (60%) or Bacillus megaterium (60%). The expression of ccpA in Thermoactinomyces sp. E79 was dependent on glucose, which is contrast to the cases of B. subtilis, B. megaterium and S. xylosus. The complementation experiment with the B. megaterium ccpA mutant indicated that the cloned gene was a ccpA.

Synthesis and biological activities of (R)-5,6-dihydro-N,N-dimethyl-4H-imidazo[4,5,1-ij]quinolin-5-amine and its metabolites.

The imidazoquinoline (R)-5,6-Dihydro-N,N-dimethyl-4H-imidazo[4,5,1-ij]quinolin-5-amine [(R)-3] is a potent dopamine agonist when tested in animals but surprisingly shows very low affinity in in vitro binding assays. When incubated with mouse or monkey liver S9 microsomes, (R)-3 is metabolized by N-demethylation and oxidation to (R)-5,6-dihydro-5-(methylamino)-4H-imidazo[4,5,1-ij]quinolin-2(1H) -one [(R)-6], intermediate metabolites, where N-demethylation to the imidazoquinoline (R)-4 and where oxidation to the imidazoquinolinone (R)-5 has taken place, are also observed in these incubates. A cross-species study on the metabolism of (R)-3 in vitro has shown large variations in the extent of metabolism from species to species. Imidazoquinolinones (R)-5 and (R)-6 have comparable activity to (R)-3 in animals and also show good dopaminergic (D2) and serotonergic (5HT1A) activities in binding assays. It is probable that these metabolites account at least in part for the in vivo activity found for (R)-3. Efficient syntheses for compounds 3-6 as single enantiomers from quinoline are presented together with information on the biological activities and metabolic stabilities of these compounds.

Pharmacology of U-91356A, an agonist for the dopamine D2 receptor subtype.

U-91356A [(R)-5,6-dihydro-5-(propylamino)4H-imidazo[4,5,1-ij]quinolin -2-(1H)-one, monohydrochloride], bound with highest affinity to the dopamine D2 receptor subtype, although it also bound with somewhat lower affinities to the dopamine D3 and D4, as well as the 5-HT1A receptor subtypes. In addition to depressing dopamine synthesis and turnover, injection of U-91356A increased striatal acetylcholine concentrations. U-91356A also depressed firing rates of dopamine neurons. In mice, this compound stimulated cage climbing and locomotor activity in reserpinized animals; it also antagonized D-amphetamine-stimulated locomotor activity. It produced contralateral turning in rats with unilateral lesions of the substantia nigra. These data are consistent with roles for the dopamine D2 receptor subtype as a dopamine autoreceptor and as a stimulatory, postsynaptic dopamine receptor.

Children with HIV becoming adolescents: caring for long-term survivors.

As children infected with HIV live longer, pediatric nurses who care for these patients need to be familiar with adolescent development and to anticipate physiologic and behavioral changes that will occur in this population. Concerns regarding confidentiality, autonomy, medication needs and compliance may become paramount. Learning how to interview adolescents and becoming comfortable with adolescent sexuality issues will enhance the patient-provider relationship.

Medicinal chemistry of imidazoquinolinone dopamine receptor agonists.

(R)-5-(Dipropylamino)-5,6-dihydro-4H-imidazo[4,5,1-ij]-quinolin-2( 1H)-on e (1a, U-86170), a potent high intrinsic activity dopamine (D2) agonist, has been prepared in eleven steps from quinoline. In several tests, the compound showed dopamine autoreceptor agonist activity at low doses. It showed postsynaptic agonist activity at somewhat higher doses, reversing the effects of reserpine in mice and increasing striatal acetylcholine levels. The compound showed some serotonergic (5HT1A) activity, but was inactive at other receptors. The related monopropylamine 2 (U-91356), also showed good dopaminergic agonist activity, and had improved metabolic stability and oral bioavailability in the rat and monkey when compared to 1a. Compounds 1a and 2 have been prepared in tritiated form, and [3H]1a (69 Ci/mmol) has found use as a D2 agonist radioligand in binding assays. The dopaminergic (D2) and serotonergic (5HT1A) activities of a series of compounds related to 1a have been evaluated using this ligand, [3H]raclopride, and [3H]8-OH DPAT.

Caring for the adolescent with HIV infection or AIDS in the critical care setting.

Caring for the adolescent with HIV infection or AIDS in the critical care setting is challenging. This article discusses medical treatments for HIV, aspects of adolescent development that influence their behaviors, certain behaviors that put adolescents at risk for HIV acquisition, ethical and legal concerns for caring for this population, nursing implications for care, and the needs of nurses caring for this population.

Dopaminergic and serotonergic activities of imidazoquinolinones and related compounds.

The synthesis of 5-(dipropylamino)-5,6-dihydro-4H-imidazo[4,5,1-ij] quinolin-2(1H)-one (5), a potent dopamine D2 agonist showing high dopamine/serotonin (5HT1A) selectivity, is described. Dopaminergic activity is associated with the (R)-enantiomer of 5; the (S)-enantiomer shows no dopaminergic activity. A series of analogues where the imidazolone ring was modified to various 5- or 6-membered heterocyclic rings were prepared. Some of these compounds showed a combination of dopaminergic and serotonergic activity, while one compound, 6-(dipropylamino)-1,2,6,7-tetrahydro-3H,5H-pyrido[3,2,1- ij]quinazolin-3-one (24), was a selective serotonergic agonist. Various analogues of 5 where the dipropylamine substituent was modified were prepared. Most of these showed reduced dopaminergic activity, while several were as potent as 5 at the serotonin 5HT1A receptor. Orientations for the new compounds at dopamine and serotonin receptors are proposed and compared with those of other tricyclic ligands known to have high affinity at these receptors.