Tissue response to covered Wallstents

8-epi prostaglandin F2alpha(8-epi PGF2alpha) contracted rat thoracic aorta rings in a concentration-dependent manner in the presence or absence of functional endothelium [median effective concentration (EC50) values, 455+/-52 and 268+/-34 nM, respectively; Student's t test; p=0.006]. U46619 was a more potent agonist with or without functional endothelium (EC50 values, 6.8+/-1.6 and 4.5+/-1.0 nM, respectively). SQ29548 [a thromboxane (TP)-receptor antagonist] inhibited contractions to both 8-epi PGF2alpha and U46619 in a competitive manner, with mean pA2 values of 8.3 and 7.9, respectively. 8-Epi PGF2alpha had a further contractile effect in vessels that had been contracted with noradrenaline and had been shown to possess a functional endothelium. Inhibition of thromboxane synthesis with OKY-046 or blockade of endothelin receptors with bosentan had no effect on responses to 8-epi PGF2alpha or U46619. Preincubation with 8-epi PGF2alpha or noradrenaline shifted the concentration-response curves to U46619 upward at low concentrations of U46619 with no significant change in EC50 values or maximal responses. Reduction of TP-receptor number in rat aorta with dithiothreitol caused a concentration-dependent inhibition of responses to both U46619 and 8-epi PGF2alpha, with no effect on maximal responses and or on the responses to U46619 after the preincubation with 8-epi PGF2alpha. These results indicate that 8-epi PGF2alpha is a potent vasoconstrictor in the rat aorta and are suggestive of an action of 8-epi PGF2alpha at the TP receptor.     

A novel simian immunodeficiency virus (SIVdrl) pol sequence from the drill monkey, Mandrillus leucophaeus

The drill monkey has been shown by serology and PCR to harbor a unique simian immunodeficiency virus (SIVdrl). A pol sequence, amplified from uncultured peripheral blood cells, is most closely related to the equivalent SIV sequences from the red-capped mangabey (SIVrcm), the sabaeus African green monkey (SIVagmSAB), and the chimpanzee (SIVcpz) and to the human immunodeficiency virus type 1 (HIV-1) sequence of humans. It is as yet unclear whether SIVdrl has a mosaic genome like SIVrcm and SIVagmSAB, is a member of the SIVcpz/HIV-1 lineage, or represents a novel primate lentivirus lineage.     

Increased glucocorticoid activity in men with cardiovascular risk factors

The association between hypertension and insulin resistance might be explained by increased activity of the principal glucocorticoid, cortisol. Recent data show that the intensity of dermal vasoconstriction after topical application of glucocorticoids is increased in patients with essential hypertension. In this report, we examine whether increased glucocorticoid sensitivity or secretion is associated with insulin resistance and is a cause or consequence of hypertension. We studied 32 men (aged 47 to 56 years) from a cross-sectional study and 105 men (aged 23 to 33 years) in whom predisposition to high blood pressure has been defined by their own blood pressure and the blood pressures of their parents. In both populations, increased dermal glucocorticoid sensitivity was associated with relative hypertension, insulin resistance, and hyperglycemia. In young men with higher blood pressure whose parents also had high blood pressure, enhanced glucocorticoid sensitivity was accompanied by enhanced secretion of cortisol, enhanced ligand-binding affinities for dexamethasone in leukocytes, and impaired conversion of cortisol to inactive metabolites (cortisone and 5beta-dihydrocortisol). Increased tissue sensitivity to cortisol, amplified by enhanced secretion of cortisol, is a feature of the familial predisposition to high blood pressure rather than a secondary effect of high blood pressure. It may be mediated by an abnormal glucocorticoid receptor, and it may contribute to the association between hypertension and insulin resistance.     

Reliability and validity of the interview and self-report versions of the BASIS-32

The psychometric properties of the interview and self-report versions of the BASIS-32 were compared. A total of 120 severely mentally ill adults enrolled in psychosocial rehabilitation were randomly assigned to either a self-report or an interview condition. The BASIS-32 had good internal consistency and test-retest reliability on most subscales; coefficients were higher in the self-report condition. Only the interview version of the psychosis subscale had unacceptable internal consistency. Validity correlations were generally good for the symptom subscales but disappointing for the functional domains. The subscale scores did not discriminate between diagnostic subgroups.     

Kinetics of CD4+ T cell repopulation of lymphoid tissues after treatment of HIV-1 infection

Potent combinations of antiretroviral drugs diminish the turnover of CD4+ T lymphocytes productively infected with HIV-1 and reduce the large pool of virions deposited in lymphoid tissue (LT). To determine to what extent suppression of viral replication and reduction in viral antigens in LT might lead correspondingly to repopulation of the immune system, we characterized CD4+ T lymphocyte populations in LT in which we previously had quantitated viral load and turnover of infected cells before and after treatment. We directly measured by quantitative image analysis changes in total CD4+ T cell counts, the CD45RA+ subset, and fractions of proliferating or apoptotic CD4+ T cells. Compared with normal controls, we documented decreased numbers of CD4+ T cells and increased proliferation and apoptosis. After treatment, proliferation returned to normal levels, and total CD4+ T and CD45RA+ cells increased. We discuss the effects of HIV-1 on this subset based on the concept that renewal mechanisms in the adult are operating at full capacity before infection and cannot meet the additional demand imposed by the loss of productively infected cells. The slow increases in the CD45RA+ CD4+ T cells are consistent with the optimistic conclusions that (i) renewal mechanisms have not been damaged irreparably even at relatively advanced stages of infection and (ii) CD4+ T cell populations can be partially restored by control of active replication without eradication of HIV-1.     

Preformulation Studies on Imexon

Abstract

Imexon is an aziridine containing iminopyrrolidone that, through aziridine ring opening, is able to induce oxidative stress resulting in apoptosis. The main objective of this research was to conduct extensive preformulation studies on Imexon in order to understand the factors that affect its stability. The results obtained indicate that the stability of Imexon is dependant on pH, ionic strength, temperature, buffer species, and initial concentration. Degradation of Imexon follows apparent first-order degradation kinetics with the primary degradation product resulting from opening of the aziridine ring. In order to maximize stability, ionic strength, temperature, and initial concentration should be minimized, with an optimal range pH between 7.2 and 9.0. Experimentation with other aqueous solutions indicates that Imexon has increased stability in D5W as opposed to normal saline, while it undergoes rapid degradation in 6% H₂O₂. Imexon is not ionizable between pH 5.0 to 8.5 and has an aqueous solubility of approximately 25 mg/mL over this range. Solid-state characterization has concluded that Imexon is a crystalline solid that begins decomposition at 165°C, prior to melting.     

Geometric characterization of stenosed human carotid arteries

RATIONALE AND OBJECTIVES: The geometry of stenosed carotid bifurcations was analyzed to determine average representations for several stenosis grades. METHODS: Film angiograms of 62 patients with internal carotid artery stenoses were digitized. Residual lumen boundaries were manually outlined. The outlines were processed with a computer to extract geometric measurements. The measurements were grouped according to stenosis grade and used to create average representations. RESULTS: Accuracy and precision of the outlining technique were +/- 0.020 common carotid diameters (CCD) and +/- 0.025 CCD, respectively. Maximum narrowing of the internal carotid artery occurred at 0.3 CCD +/- 1.5 (mean +/- standard deviation) distal to the flow divider. The region of significant narrowing extended axially 1.2 CCD +/- 1.0. Poststenotic dilatations were observed, with enlargement of 1.3 +/- 0.7 times the normal diameter of the distal internal carotid artery. A tendency toward smaller bifurcation angles with increasing stenosis severity was observed. CONCLUSION: Three-dimensional geometric models could be created for carotid bifurcations that were disease free (normal) and of arbitrary stenosis grade.