The dietary supplement ephedrine induces beta-adrenergic mediated exacerbation of systemic lupus erythematosus in NZM391 mice.

The dietary supplement and adrenergic receptor agonist ephedrine has been a controversial topic as its safety has been questioned. Beta-adrenergic receptor (beta-AR) activation causes immunomodulation, which may contribute to promotion of autoimmune pathology. This report investigated the ability of ephedrine to exacerbate processes associated with autoimmune disease in a lupus-prone mouse model. To mimic human supplementation, ephedrine was administered to NZM391 (lupus-prone) and BALB/c (nonlupus prone) mice orally twice a day for three months at a dose of 50 and 100 microg/day. Some ephedrine-treated NZM391 mice also were preadministered the beta-AR antagonist propranolol to investigate beta-AR involvement. Mice were bled monthly, and sera were assayed for a variety of lupus manifestations and immunological measurements. In NZM391 males and females, both doses of ephedrine significantly increased lupus manifestations, including IgG production and organ-directed autoantibody titers, and significantly lowered the ratio of IgG2a/IgG1 compared to controls. Ephedrine significantly decreased female lifespan and significantly increased circulating populations of plasma cells (CD38(hi) CD19(lo) cytoplasmic IgG+) and CD40+ B1a cells, while preventing an age-related decrease in the B1a cell population expressing a high level of CD5. While ephedrine induced gender-specific immunomodulation in BALB/c mice, increases in the lupus manifestations of anti-dsDNA titers and serum urea nitrogen were not detected. Preadministration of propranolol decreased lupus manifestations and serum levels of IgG and IgE in ephedrine-treated mice, but did not block the shift towards IgG1 production. These findings indicate that ephedrine via beta-AR can exacerbate lupus symptoms in NZM391 mice and that blockade of the beta-ARs on B cells, and not T cells, apparently was of greater importance as the inhibition of lupus symptoms corresponded to an inhibition of immunoglobulin levels, not a change of Th1/Th2 balance.

Venous valve station changes in "primary" and postthrombotic reflux: an analysis of 149 cases.

The purpose of this study was to analyze valve station changes noted during venous valve reconstruction and the associated outcome. One hundred and forty-nine valve reconstructions were available for analysis at the time of surgical exploration; the venous valve was graded according to valve station changes (VS grades) from zero through six. Ascending venography was analyzed by a similar grading system and the two methods were compared. The results of this analysis showed that valve station wall changes are frequently present in patients with deep venous reflux and pose technical challenges during valve reconstruction; the outcome, however, appears unaffected. Grade 0 to 1 valve station changes are predominantly due to "primary" reflux, with an occasional instance of postthrombotic etiology. Grade 2 or 3 valve station changes are roughly evenly divided between phlebosclerosis of primary reflux and postthrombotic etiologies. The mechanism of onset of reflux with preservation of valve cusps in the latter group of postthrombotic cases is probably different from currently accepted theories of evolution of postthrombotic changes. Postthrombotic valve damage is variable, and the valve station anatomy may be sufficiently preserved in some patients to allow direct valve repair.

Studies in calf venous pump function utilizing a two-valve experimental model.

OBJECTIVES: to explore the hydrodynamic mechanisms involved in the regulation of ambulatory venous pressure. DESIGN: an experimental model of calf venous pump was constructed with collapsible tubes and valves. MATERIAL: the model consisted of a conduit and a pump with an intervening competent valve. Another valve that could allow reflux into the pump was mounted above the pump. METHODS: conduit pressure and recovery times were monitored under conditions of different degrees of ejection fraction and reflux into the pump. Model variables included using poorly compliant tubes for the pump, the conduit and for both the pump and conduit. RESULTS: the latex tube exhibited a non-linear volume-pressure relationship and a bi-modal regimen of compliance. This bestowed pressure-buffering properties. Ambulatory venous hypertension resulted when reflux beyond buffering capacity occurred. Substituting less compliant PTFE for latex at the pump had a relatively minor effect on post-ejection pressure and recovery times. Using PTFE at the conduit had a profound but divergent effect on both of these parameters. Conduit capacitance reduction had a similar effect. CONCLUSION: conduit elastance plays a significant role in the regulation of ambulatory venous pressure in this experimental model. The hydrodynamic principles illustrated by the model may enhance our understanding of the human calf venous pump.

Interactions between benzylamiloride and fura-2: studies in vitro and in cardiac myocytes.

Amiloride derivatives are commonly used inhibitors of Na+/H+- and Na+/Ca2+-exchange. Because they are fluorescent molecules the use of benzylamiloride (BZA), an inhibitor of Na+/Ca2+ exchange, in conjunction with Fura-2, a commonly used fluorescent Ca2+ indicator, might complicate interpretation of fluorescence data obtained. In vitro data show that BZA decreases the Fura-2 fluorescence at all useful wavelengths in a concentration-dependent manner. The Fura-2 ratio 340/380 (used to estimate intracellular Ca2+ ([Ca2+]in)) also decreased with increasing BZA concentrations. The Stern-Volmer relation suggests that this phenomenon is due to either static or dynamic quenching. Varying temperatures from 4 to 37 degreesC did not alter Stern-Volmer constants, consistent instead with fluorescence resonance energy transfer (FRET). The in situ relevance of these interactions was evaluated in adult rat cardiac myocytes which exhibit Na+/Ca2+ exchange reflected by rapid [Ca2+]in increase following Na+ removal. Pretreatment with BZA >/= 25 microM decreased the magnitude of Fura-2 changes induced by Na+ removal. Analysis of the individual Fura-2 useful wavelengths indicated that >/= 25 microM BZA altered the Fura-2 signal in a manner consistent with the quenching effects noted in vitro. Together, these data show that BZA interacts with Fura-2 in vitro and in situ and suggest caution when interpreting Fura-2 fluorescence data derived in conjunction with BZA.

Tube collapse and valve closure in ambulatory venous pressure regulation: studies with a mechanical model.

PURPOSE: To determine the role of valve closure and column segmentation in ambulatory venous pressure regulation. METHODS: Using a mechanical model consisting of a graduated adjustable valve and a collapsible tube, we studied the differential effects of valve closure and tube collapse on venous pressure regulation. By utilizing materials with differing wall properties for the infravalvular tube, the influence of wall property changes on tube function and pressure regulation was explored. RESULTS: Valve closure, per se, does not cause venous pressure reduction. Collapse of the tube below the valve is the primary pressure regulatory mechanism. The nonlinear volume-pressure relationship that exists in infravalvular tubes confers significant buffering properties to the collapsible tube, which tends to retain a near-constant pressure for a wide range of ejection fractions, residual tube volumes, and valve leaks. Changes in tube wall property affect this buffering action, at both the low and high ends of the physiological venous pressure range. CONCLUSIONS: The valve and the infravalvular venous segment should be considered together in venous pressure regulation. Tube collapse of the segment below the valve is the primary pressure regulatory mechanism. An understanding of the hydrodynamic principles involved in pressure regulation derived from this model will provide the basis for construction of more complex models to explore clinical physiology and dysfunction.

Health effects and exposure assessment of aerosolized pentamidine handlers.

Nurses administering aerosolized pentamidine (AP) were studied to determine any effect AP may be having on their health. Exposure was determined by each nurse's self-report of treatment given as recorded in a daily log and personal and area pentamidine sampling. Outcome measures were self-reported symptoms recorded in a daily log and peak expiratory flow rates (PEFR) and cross-shift and cross-week pulmonary function tests (PFTs). Results revealed no dose-response effect of pentamidine exposure on cross-shift and cross-week PFTs. However, declines in cross-shift PEFRs, diffusion capacities, and increased symptom complaints were observed for a subset of the study population. This suggested that outcomes were modulated by host factors (history of hay fever and allergy) as well as exposure doses. Treatment both efficacy in containing fugitive AP aerosol was also corroborated as a means of minimizing worker exposure.

A stable-isotope study of zinc, copper, and iron absorption and retention by young women fed vitamin B-6-deficient diets.

A 98-d study was conducted in young women to determine the effect of vitamin B-6-deficient diets on zinc, copper, and iron metabolism. Young women were fed vitamin B-6-deficient formula initially, followed by food diets containing four increasing amounts of vitamin B-6. Zinc, copper, and iron absorption, retention, and status were determined at intervals throughout the study. Zinc absorption and retention were greater during vitamin B-6 depletion but serum zinc declined, suggesting that absorbed zinc was not available for utilization. Copper absorption was lower during vitamin B-6 depletion but serum copper was not affected and balance was positive. Iron absorption was not impaired significantly by vitamin B-6-deficient diets but status may have declined. The results suggest that vitamin B-6 depletion of young women may alter zinc metabolism, inhibit copper absorption, and affect iron status. The effects of vitamin B-6 depletion differ markedly among these elements.

Protein utilization by young women consuming animal or plant protein diets at various levels of vitamin B-6 intake.

Eight young women consumed a vitamin B-6 depletion diet (egg albumen formula, less than 0.05 mg vitamin B-6/d) for 11-28 d. Subjects (n = 4) then consumed either animal protein (AP, mainly dairy and poultry products) or plant protein (PP, mainly various types of beans) diets with increasing vitamin B-6 intake (0.5, 1.0, 1.5, and 2.0 mg/d) for periods of 14-21 d. All diets provided 1.55 g protein/kg body wt. Apparent protein digestibility of AP (94.6%) was significantly higher than that of PP (88.4%) diets (p less than 0.001). Protein digestibility was not significantly affected by vitamin B-6 intake. Apparent nitrogen balance of subjects consuming AP diets was slightly, though not significantly, higher than that of subjects fed PP diets. N balance was not influenced by vitamin B-6 intake. Data suggest that short-term low vitamin B-6 intake does not affect protein utilization in humans as determined by digestibility and N balance.

Bioavailability of vitamin B-6 from rat diets containing wheat bran or cellulose.

Bioavailability of vitamin B-6 (B-6) in the total diet was studied in male, weanling Sprague-Dawley rats fed fiber-free (FF) diets with 0.2 or 6.9 mg pyridoxine/kg diet (0-, 2- or 6.9-PYR), 20% wheat bran (WB) diets with 3.9- or 5.5-PYR or 7% cellulose (C) diets with 0- or 2-PYR for 28 d. Body weight gain (mean +/- SEM) with 0-PYR was 70 +/- 9.0 and 81.2 +/- 4.2 g for FF and C, respectively. All other groups gained 170-180 g. Urinary excretion of 4-pyridoxic acid (4-PA), a major B-6 metabolite, for FF groups was 1.31 +/- 0.22, 2.26 +/- 0.28 and 6.39 +/- 1.73 micrograms/24 h, at 0-, 2- and 6.9-PYR, respectively. Rats fed WB diets excreted 4.99 +/- 0.58 and 9.81 +/- 0.76 micrograms/24 h (3.9- and 5.5-PYR, respectively) and those fed C diets excreted 1.46 +/- 0.34 and 2.69 +/- 0.72 micrograms/24 h (0- and 2-PYR). There was increasing turnover and shorter biological half-life of [14C]pyridoxine (1 mu Ci injected on d 1) with increasing dietary B-6. Growth, 4-PA and 14C turnover data indicated that WB contributed to B-6 intake of these rats. Cellulose acted as a simple dietary diluent and had no effect on indices of B-6 status. These data suggest that dietary fiber, as cellulose or the indigestible component of wheat bran, does not adversely affect the bioavailability of vitamin B-6.

Computers in manufacturing.

Computers are now widely used in product design and in automation of selected areas in factories. Within the next decade, the use of computers in the entire spectrum of manufacturing applications, from computer-aided design to computer-aided manufacturing and robotics, is expected to be practical and economically justified. Such widespread use of computers on the factory floor awaits further advances in computer capabilities, the emergence of systems that are adaptive to the workplace, and the development of interfaces to link islands of automation and to allow effective user communications.