Health promotion for the oldest of old people.

AIM: The aim of this study was to explore the factors that contribute to health promotion in the oldest old and the barriers that prevent it. METHOD: A non-random sample (n = 52) of people aged 80 and older participated in a descriptive correlational study. Respondents completed a series of two Likert-type questionnaires. The Health Promoting Lifestyle Profile II (Walker et al 1995) and Barriers to Health Promoting Activities for Disabled Persons Scale (Becker et al 1991) were used to measure health behaviours. RESULTS: Differences were noted between the age groups (80-90 and 91-101) for health responsibility, physical activity and nutrition. Impairment was the major barrier to health promotion. CONCLUSION: To foster optimal living, the health, illness, function and motivation as well as age of older adults must be considered. They should be encouraged to pursue physical, social and intellectual activity, which can enable them to have active and fulfilling lives.

Aging in America: quality of life among older Vietnamese women immigrants.

The purpose of this ethnographic research was to describe factors related to and elicit the meaning of "quality of life" in a group of older Vietnamese women immigrants. Thirty-three women who emigrated from Vietnam to the United States after 1978 participated in audiotaped interviews. Ethnographic content analysis was used to identify themes and categories. Major theme ofresiliency and security were identified. The elements of health, functional status and social support were consistent with quality of life concepts described by Flanagan; and, George and Bearon while leisure and recreation was not present.

Potent, orally bioavailable, liver-selective stearoyl-CoA desaturase (SCD) inhibitors.

Two structurally distinct series of SCD (Delta9 desaturase) inhibitors (1 and 2) have been previously reported by our group. In the present work, we merged the structural features of the two series. This led to the discovery of compound 5b (CVT-12,012) which is highly potent in a human cell-based (HEPG2) SCD assay (IC(50)=6nM). This compound has 78% oral bioavailability in rats and is preferentially distributed into liver (76 times vs plasma) with relatively low brain penetration. In a five-day study (sucrose fed rats) compound 5b significantly reduced SCD activity in a dose-dependent manner as determined by GC analysis of fatty acid composition in plasma and liver, and significantly reduced liver triglycerides versus the control group ( approximately 50%).

Orally bioavailable, liver-selective stearoyl-CoA desaturase (SCD) inhibitors.

We discovered a structurally novel SCD (Delta9 desaturase) inhibitor 4a (CVT-11,563) that has 119 nM potency in a human cell-based (HEPG2) SCD assay and selectivity against Delta5 and Delta6 desaturases. This compound has 90% oral bioavailability (rat) and excellent plasma exposure (dAUC 935 ng h/mL). Additionally, 4a shows moderately selective liver distribution (three times vs plasma and adipose tissue) and relatively low brain penetration. In a five-day study (high sucrose diet, rat) compound 4a significantly reduced SCD activity as determined by GC analysis of fatty acid composition in plasma and liver. We describe the discovery of 4a from HTS hit 1 followed by scaffold replacement and SAR studies focused on DMPK properties.

Characterization of the potency, selectivity, and pharmacokinetic profile for six adenosine A2A receptor antagonists.

Antagonists of adenosine A2A receptors (A2A -antagonists) with different chemical structures have been developed by several pharmaceutical companies for the potential treatment of Parkinson's disease. Pharmacological characterization of these antagonists was incomplete, and different assay conditions were used in different labs. Therefore, we characterized the potencies, selectivities, and pharmacokinetic profiles of six prototypical A2A -antagonists. Displacements of [3H]MSX-2 and of [3H]CGS21680 binding to the human cloned and rat A2A receptors were performed. The rank order of potency of antagonists to displace [(3)H]MSX-2 binding to the human A2A was SCH58261 > or = Biogen-34 > or = Ver-6623 > or = MSX-2 > KW-6002 > > DMPX. For the rat striatal A2A, the order of potency was Biogen-34 > or = SCH58261 > or = Ver-6623 > or = MSX-2 > or = KW-6002 > > DMPX. SCH58261 was the most potent antagonist of the human A2A with a K(i) value of 4 nM, whereas Biogen-34 was the most potent antagonist of the rat A2A with a K(i) value of 1.2 nM. Similar results were obtained from cAMP assays. Selectivities of A2A-antagonists were determined using radioligands [3H]DPCPX, [3H]ZM241385, and [125I]-AB-MECA for A1, A2B, and A3 receptors, respectively. KW-6002 and Biogen-34 exhibited the highest selectivity for A2A vs A1 (human and rat), respectively. The pharmacokinetic profiles of antagonists were evaluated in vivo in rats. DMPX and KW-6002 had the greatest oral bioavailability. In contrast, SCH58261, MSX-2, and Ver-6623 had low or poor oral bioavailability. In summary, SCH58261, Biogen-34, MSX-2, and Ver-6623 had high affinities for both human and rat A2A receptors, with reasonable selectivity for A2A over A1 and A2B receptors. They are suitable as A2A -antagonists for in vitro pharmacological studies. Among the six A2A-antagonists, KW-6002 is the best for use in in vivo animal studies, particularly for a CNS target, based on its bioavailability, half life, and brain penetration.

Dose indices of radiation to skin in fluoroscopically guided invasive cardiology procedures.

Tissue injury depends on the extent as well as the intensity of the assault. It would be helpful to develop skin dose indices that are more descriptive of the skin area receiving radiation above a threshold value of potential injury. For monitoring radiation exposure to patients, radiochromic film was placed close to the skin of a patient undergoing cardiac catheterization procedures. With the approval of the Institutional Review Board, films from 36 patients were scanned. Contours were drawn at the increment of 100 cGy in air kerma. Using each contour value as a threshold, the area exceeding this threshold and the average dose within this area were computed. For the four patients who had skin doses exceeding the 200 cGy threshold, the peak entrance doses have a range from 230 cGy to 409 cGy. However, these high radiation exposures were confined to limited skin areas and support the absence of any significant skin injury in these patients. The area exceeding a chosen threshold value and the average dose within the area circumscribed might therefore serve as helpful measures of the assault to the skin. This investigation has demonstrated the technical feasibility of providing such dose indices.

Studies to investigate the pharmacokinetic interactions between ranolazine and ketoconazole, diltiazem, or simvastatin during combined administration in healthy subjects.

The interactions of ranolazine, a new antianginal compound, with inhibitors and substrates of the CYP3A isoenzyme family were studied in 1 open-label and 4 double-blind, randomized, multiple-dose studies. In healthy adult volunteers, the authors sought (1) to determine the steady-state pharmacokinetics, safety, and tolerability of immediate- and sustained-release ranolazine with and without ketoconazole, diltiazem, or simvastatin and (2) to evaluate the effect of ranolazine on the pharmacokinetics of diltiazem, simvastatin, simvastatin metabolites, and HMG-CoA reductase activity. Ketoconazole increased ranolazine plasma concentrations and reduced the CYP3A4-mediated metabolic transformation of ranolazine, confirming that CYP3A4 is the primary metabolic pathway for ranolazine. Diltiazem reduced oral clearance of ranolazine in a dose-dependent manner. Simvastatin did not affect ranolazine pharmacokinetics, although ranolazine increased the AUC and C(max) of simvastatin, simvastatin acid, 2 simvastatin metabolites, and HMG-CoA reductase activity by <2-fold. Administration of ranolazine in combination with diltiazem or simvastatin was safe and well tolerated during the interval studied.

Culturally competent scholarship in nursing research.

PURPOSE: To determine the degree to which research reports published in major nursing research journals reflected Meleis's eight criteria for culturally competent scholarship. DESIGN: Analytic review of 167 studies dealing with race, ethnicity, or culture from four nursing research journals, 1992-2000. METHOD: Four reviewers selected, abstracted, and scored research articles independently, in pairs, and as a group. FINDINGS: The mean and median Meleis scores were 2.92 and 3.00 on an 8-point scale. All scores were assigned at least once. Contextuality, relevance, and communication style were most frequently present; disclosure, empowerment, and time were least frequently present. IMPLICATIONS: Assignment of Meleis scores is feasible and useful for evaluating cultural competence of research reports.

A facile approach to prepare silicon-based Pt-Ag tubular dendritic nano-forests (tDNFs) for solar-light-enhanced methanol oxidation reaction.

In this paper, a facile two-step Galvanic replacement reaction (GRR) is proposed to prepare Pt-Ag tubular dendritic nano-forests (tDNFs) in ambient condition for enhancing methanol oxidation reaction (MOR) under solar illumination. In the first GRR, a homogeneous layer of silver dendritic nano-forests (DNFs) with 10 µm in thickness was grown on Si wafer in 5 min in silver nitride (AgNO3) and buffer oxide etchant (BOE) solution. In the second GRR, we utilized chloroplatinic acid (H2PtCl6) as the precursor for platinum (Pt) deposition to further transform the prepared Ag DNFs into Pt-Ag tDNFs. The catalytic performance and solar response of the Pt-Ag tDNFs toward methanol electro-oxidation are also studied by cyclic voltammetry (CV) and chronoamperometry (CA). The methanol oxidation current was boosted by 6.4% under solar illumination on the Pt-Ag tDNFs due to the induced localized surface plasmon resonance (LSPR) on the dendritic structure. Current results provide a cost-effective and facile approach to prepare solar-driven metallic electrodes potentially applicable to photo-electro-chemical fuel cells.

Inhibition of aldehyde dehydrogenase-2 suppresses cocaine seeking by generating THP, a cocaine use-dependent inhibitor of dopamine synthesis.

There is no effective treatment for cocaine addiction despite extensive knowledge of the neurobiology of drug addiction. Here we show that a selective aldehyde dehydrogenase-2 (ALDH-2) inhibitor, ALDH2i, suppresses cocaine self-administration in rats and prevents cocaine- or cue-induced reinstatement in a rat model of cocaine relapse-like behavior. We also identify a molecular mechanism by which ALDH-2 inhibition reduces cocaine-seeking behavior: increases in tetrahydropapaveroline (THP) formation due to inhibition of ALDH-2 decrease cocaine-stimulated dopamine production and release in vitro and in vivo. Cocaine increases extracellular dopamine concentration, which activates dopamine D2 autoreceptors to stimulate cAMP-dependent protein kinase A (PKA) and protein kinase C (PKC) in primary ventral tegmental area (VTA) neurons. PKA and PKC phosphorylate and activate tyrosine hydroxylase, further increasing dopamine synthesis in a positive-feedback loop. Monoamine oxidase converts dopamine to 3,4-dihydroxyphenylacetaldehyde (DOPAL), a substrate for ALDH-2. Inhibition of ALDH-2 enables DOPAL to condense with dopamine to form THP in VTA neurons. THP selectively inhibits phosphorylated (activated) tyrosine hydroxylase to reduce dopamine production via negative-feedback signaling. Reducing cocaine- and craving-associated increases in dopamine release seems to account for the effectiveness of ALDH2i in suppressing cocaine-seeking behavior. Selective inhibition of ALDH-2 may have therapeutic potential for treating human cocaine addiction and preventing relapse.

Comparison of symptomatology in Taiwanese women pregnant with and without assisted reproductive technology.

We compared the symptoms of 91 Taiwanese women, 50 pregnant by assisted reproductive technology (ART), with those of 41 women, pregnant without assistance. They completed a self-administered demographic questionnaire and symptomatology inventory (SI) during each trimester. The ART group had a higher frequency of complications and hospitalizations than the unassisted women. No significant differences were found in physical and affective symptoms in the ART group across three trimesters, but significant differences were found in the unassisted group. In addition, ART and non-ART women differed in types of individual symptoms experienced each trimester. These findings suggest the need for nurses to assess each group for the presence of specific symptoms throughout pregnancy and to provide individualized symptom management.

The discovery of a selective, high affinity A(2B) adenosine receptor antagonist for the potential treatment of asthma.

Adenosine has been suggested to play a role in asthma, possibly via activation of A(2B) adenosine receptors on mast cells and other pulmonary cells. We describe our initial efforts to discover a xanthine based selective A(2B) AdoR antagonist that resulted in the discovery of CVT-5440, a high affinity A(2B) AdoR antagonist with good selectivity (A(2B) AdoR K(i)=50 nM, selectivity A(1)>200: A(2A)>200: A(3)>167).

Novel inhibitors of fatty acid oxidation as potential metabolic modulators.

We describe the synthesis of novel inhibitors of fatty acid oxidation as potential metabolic modulators for the treatment of stable angina. Replacement of the 2H-benzo[d]1,3-dioxolene ring system in our initial lead 3 with different benzthiazoles, benzoxazoles and introducing small alkyl substituents into the piperazine ring resulted in analogues with enhanced inhibitory activity against 1-(14)[C]-palmitoyl-CoA oxidation in isolated rat heart mitochondria (6, IC(50)=70 nM; 25, IC(50)=23 nM).

Affinity and intrinsic efficacy (IE) of 5'-carbamoyl adenosine analogues for the A1 adenosine receptor--efforts towards the discovery of a chronic ventricular rate control agent for the treatment of atrial fibrillation (AF).

The SAR for the affinity to the A(1) adenosine receptor and relative intrinsic efficacy (IE, [(35)S]-GTPgammaS binding) of a series of 5'-carbamate and 5'-thionocarbamate derivatives of tecadenoson is described. Based on this SAR, selected compounds were evaluated in guinea pig isolated hearts to determine whether they were partial or full agonists with respect to their negative dromotropism, an A(1) AdoR mediated effect. Progress towards obtaining a partial A(1) AdoR agonist to potentially control ventricular rate during atrial fibrillation has been made with the discovery of several potent partial A(1) AdoR agonists (compounds 13, 14, and 17).

CVT-4325: a potent fatty acid oxidation inhibitor with favorable oral bioavailability.

New inhibitors of palmitoyl-CoA oxidation are based on the introduction of nitrogen heterocycles in the 'Western Portion' of the molecule. SAR studies led to the discovery of CVT-4325 (shown), a potent FOXi (IC50=380 nM rat mitochondria) with favorable PK properties (F=93%, t(1/2)=13.6h, dog).

New fatty acid oxidation inhibitors with increased potency lacking adverse metabolic and electrophysiological properties.

New inhibitors of palmitoylCoA oxidation were synthesized based on a structurally novel lead, CVT-3501 (1). Investigation of structure-activity relationships was conducted with respect to potency of inhibition of cardiac mitochondrial palmitoylCoA oxidation and metabolic stability. Potent and metabolically stable analogues 33, 42, and 43 were evaluated in vitro for cytochrome P450 inhibition and potentially adverse electrophysiological effects. Compound 33 was also found to have favorable pharmacokinetic properties in rat.