Alveolar permeability enhancement by oleic acid and related fatty acids: evidence for a calcium-dependent mechanism

Pulmonary exposure to oleic acid (OA) is associated with permeability alterations and cellular damage; however, the exact relationship between these two effects has not been clearly established. Using cultured alveolar epithelial monolayers, we demonstrated that OA and some other fatty acids (< or = 50 microM) can induce permeability changes without detectable cellular damage. At higher concentrations, however, OA caused severe membrane damage and leakage to solute flux. The permeability enhancing effect of OA was observed with both the paracellular marker 3H-mannitol and the lipophilic transcellular indicator 14C-progesterone. While the effect of OA on transcellular permeability may be attributed to its known effect on membrane fluidity, the paracellular promoting effect of OA and its mechanism are not well established. We postulated that OA may increase paracellular permeability through a Ca(2+)-dependent tight junction mechanism. Using dual-excitation fluorescence microscopy, we demonstrated that OA can increase intracellular calcium, [Ca2+]i, in a dose-dependent manner. This effect was transient at low OA concentrations (< or = 50 microM) but became more pronounced and sustained at higher concentrations. Free hydroxyl and unsaturated groups were required for this activation since esterified OA (oleic methyl ester) and stearic acid (a saturated fatty acid with equal chain length) had much reduced effects on both the [Ca2+]i and the permeability alterations. Degree of unsaturation was unimportant since linolenic acid (18:3), linoleic acid (18:2), and OA (18:1) had similar and comparable effects on the two parameters.(ABSTRACT TRUNCATED AT 250 WORDS)     

Protective effect of RibCys following high-dose irradiation of the rectosigmoid

Ribose-cysteine (RibCys) is a prodrug of L-cysteine that stimulates glutathione biosynthesis. Increased glutathione levels have been shown to have a protective effect against radiation-induced injury and oxidative stress. Surface oximetry has previously been used successfully to predict anastomotic leakage. PURPOSE: The following study was done to evaluate the protective effect of RibCys and the predictive value of PtO2 determinations in a swine model. METHODS: Domestic swine were divided into three groups: Group A served as a nonradiated control; Group B received 6,000 to 6,500 rad to the rectosigmoid; and Group C received RibCys (1 g/kg) prior to receiving 6,000 to 6,500 rad. Radiated animals and controls underwent rectosigmoid resection after a three-week rest period. Intraoperative anastomotic PtO2 was checked with a modified Clark electrode. Anastomoses were evaluated radiographically at three and seven days; animals were sacrificed, and bursting strength was recorded at 10 days. RESULTS: Mean bursting pressures were 243.8 +/- 59.4, 199.5 +/- 37.8, and 209.5 +/- 54.9 mmHg (NS) for Groups A, B, and C, respectively. Anastomotic PtO2 ranged from 19 to 98 mmHg and could not be correlated with anastomotic leaks or bursting pressure. There were 11/15 radiation-related deaths and leaks (eight deaths and three leaks) in the radiated group and 4/12 radiation-related deaths and leaks (three deaths and one leak) in the group receiving radiation and RibCys (P < 0.04). CONCLUSIONS: 1) RibCys protected animals against radiation-related deaths and anastomotic leaks following high doses of pelvic irradiation; 2) anastomotic PtO2 levels did not correlate with anastomotic healing in this model.     

Critical issues in mental health service delivery: what are the priorities?

The director, one other professional, and one para-professional in 515 community mental health centers and 193 state hospitals throughout the United States were asked to rate 57 critical issues in mental health services as to their importance now and five years from now. Issues judged most important now are services for children and for adolescents; five years from now children's services still top the list. Answers to two other questions revealed that respondents placed research on prevention at the top of a list of needed research areas, and that the most useful NIMH service to agencies was person-to-person assistance such as consultation and workshops.     

A galactosidase immunosorbent test for human immunoglobulin E

We report here the development of a galactosidase-immunosorbent test (GIST) for immunoglobulin E (IgE) antibodies in which the amount of galactosidase adsorbed to a cellulose disc is a single valued function of IgE concentration in human serum. Rabbit anti-IgE immunoglobulin insolubilized on cellulose discs is incubated sequentially with human serum, sheep anti-IgE serum, and a covalent conjugate of rabbit antisheep immunoglobulin with the enzyme beta-D-galactoside galactohydrolase (E.C.) 3.2.1.23). Colorimetric assay of enzyme conjugate adsorbed to discs permits quantitation of 1.0 to 25 ng of IgE per test. Concentrations of IgE in 48 sera as measured by the GIST gave a linear correlation coefficient of 0.97 with IgE concentrations as determined by radioimmunoassay. Preliminary studies indicate that the GIST makes possible nonisotopic measurement of ragweed-specific IgE antibiotics in human serum. The GIST for IgE is simple to perform and requires neither short-lived radioisotopes, expensive scintillation detection equipment, nor scarce, purified IgE.     

Cardiovascular effects of ajmaline

Ajmaline, a rauwolfia derivative, has been found to possess potent antiarrhythmic effects. The present study has been designed to define the cardiovascular effects of this drug. Hemodynamic studies performed in anesthetized and conscious dogs demonstrated no significant changes in measured hemodynamic parameters at doses equal to or less than 2 mg. per kilogram. Studies in isolated papillary muscle demonstrated no negative inotropic effects until concentrations of 1 X 10(-4). Disparate results were obtained with regard to heart rate reflecting the state of autonomic tone. Electrophysiologic studies in both anesthetized and conscious dogs demonstrated a significant depression of intraventricular conduction with no significant effect on AV nodal conduction; ventricular automaticity was not affected. Ajmaline did not alter digitalis-induced AV nodal conduction prolongation. However, ajmaline dramatically altered or abolished ventricular arrhythmias secondary to acute ischemia. In conclusion, these studies demonstrate that ajmaline specifically depresses intraventricular conduction, suggesting that this drug would be particularly effective in the treatment of re-entrant ventricular arrhythmias.