Assessment of systemic corticosteroid activity

AbstractThe potency of the inhaled corticosteroid, dose, duration of treatment, and the study subject receiving treatment all play a role in the effects observed on the HPA axis. At low/medium doses of inhaled corticosteroids, where there is minimal/modest HPA axis suppression, there should be no risk of adrenal crisis even under stressful conditions (6). Thus, the risk of acute adrenal insufficiency, culminating in adrenal crisis, in patients taking inhaled steroids is extremely unlikely

Moving from Professionalism to Political Advocacy in the Human Services--How to Organize a Successful Statewide Political Effort in Youth Services

The current funding environment makes political advocacy on the part of social work professionals mandatory. The social work literature on political advocacy is reviewed and categorized into schools of thought. The major portion of the paper, however, presents and then analyzes a case study of a statewide youth services association in order to gain more insight into how professional social workers can develop and use more successful political strategies and tactics

Creating a Positive Future for a Minority Community: Transportation and Urban Renewal Politics in Miami

Overtown, once the center of African American life in Miami, lost 40% of its population when Interstate 95 was built through the heart of the community in the 1960s. Even though a variety of non-policy factors played a role in the decline of the area, expressway construction and urban renewal greatly accelerated the process. Just as important, efforts to mitigate the impact of the highway were delayed for many years, thus magnifying the negative effects of public policies. The political barriers preventing the redevelopment of Overtown are described and analyzed. The future of Overtown is critically examined and evaluated

Genetic Analyses of the Chimeric CYP11B1/CYP11B2 Gene in a Korean Family with Glucocorticoid-Remediable Aldosteronism

Glucocorticoid-remediable aldosteronism (GRA) is an autosomal-dominant inheritable form of hyperaldosteronism with early onset hypertension. GRA is caused by unequal crossing-over of the steroid 11β-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) genes. As a result of chimeric gene duplication, aldosterone is ectopically synthesized in the adrenal zona fasciculata under the control of adrenocorticotropin. Here, we describe three cases of GRA in a Korean family. The proband-a 21-yr-old female-was incidentally found to have high blood pressure (170/108 mmHg). Her 46-yr-old father had been treated twice for cerebral hemorrhage at the ages of 29 and 39 yr. Her 15-yr-old brother had a 2-yr history of hypertension; however, he was never treated. Their laboratory test results showed normokalemia, hyporeninemia, hyperaldosteronism, and a high plasma aldosterone concentration-to-plasma renin activity ratio. Normal saline loading failed to suppress aldosterone secretion. However, dexamethasone administration effectively suppressed their plasma aldosterone concentrations. Following genetic analyses with PCR and direct sequencing to document the chimeric gene and crossover site, respectively, we identified CYP11B1/CYP11B2 and determined the breakpoint of unequal crossover to be located between intron 2 of CYP11B1 and exon 3 of CYP11B2

Structure and conformation of the disulfide bond in dimeric lung surfactant peptides SP-B1–25 and SP-B8–25

AbstractRaman spectroscopy was used to determine the conformation of the disulfide linkage between cysteine residues in the homodimeric construct of the N-terminal alpha helical domain of surfactant protein B (dSP-B1–25). The conformation of the disulfide bond between cysteine residues in position 8 of the homodimer of dSP-B1–25 was compared with that of a truncated homodimer (dSP-B8–25) of the peptide having a disulfide linkage at the same position in the alpha helix. Temperature-dependent Raman spectra of the S–S stretching region centered at ∼500 cm−1 indicated a stable, although highly strained disulfide conformation with a χ(CS–SC) dihedral angle of ±10° for the dSP-B1–25 dimer. In contrast, the truncated dimer dSP-B8–25 exhibited a series of disulfide conformations with the χ(CS–SC) dihedral angle taking on values of either ±30° or 85±20°. For conformations with χ(CS–SC) close to the ±90° value, the Raman spectra of the 8–25 truncated dimers exhibited χ(SS–CC) dihedral angles of 90/180° and 20–30°. In the presence of a lipid mixture, both constructs showed a ν(S–S) band at ∼488 cm−1, corresponding to a χ(CS–SC) dihedral angle of ±10°. Polarized infrared spectroscopy was also used to determine the orientation of the helix and β-sheet portion of both synthetic peptides. These calculations indicated that the helix was oriented primarily in the plane of the surface, at an angle of ∼60–70° to the surface normal, while the β structure had ∼40° tilt. This orientation direction did not change in the presence of a lipid mixture or with temperature. These observations suggest that: (i) the conformational flexibility of the disulfide linkage is dependent on the amino acid residues that flank the cysteine disulfide bond, and (ii) in both constructs, the presence of a lipid matrix locks the disulfide bond into a preferred conformation