Regional and species differences in vascular reactivity to extracellular potassium

In-vitro vasoreactivity to extracellular potassium (Ko+) was tested in isolated human pial and mesenteric arteries as well as basilar and mesenteric arteries from rabbits and rats. Contractions were induced by stepwise increases in [K+]o and were measured isometrically with a force-displacement transducer, in small-volume organ baths. Significant differences between species as well as between regions were found. The threshold of [K+]o for eliciting contraction in human cerebral arteries in hyperosmotic solutions was 10 mM, in rabbit cerebral arteries 17 mM and in rat cerebral arteries 27 mM. The threshold concentration for contraction in mesenteric arteries was significantly higher compared to cerebral arteries in humans and rabbits, but lower in rats: 20 mM in humans, 26 mM in rabbits and 25 mM in rats. In all species the contractile amplitudes were significantly higher in both cerebral and mesenteric arteries when [K+]o was increased under isotonic conditions in the buffer solution than when hyperosomolality was created. This difference increased with increasing hyperosmolality. In hyperosmotic solutions, the EC50 for [K+]o was lower in cerebral and mesenteric arteries from man than in vessels from rabbit and rat. When the solutions were isotonic, this pattern was seen only in mesenteric arteries. It is concluded that significant species and regional differences in vascular responses to [K+]o exist. Considering that [K+]o is increased in cerebral ischaemia, the observed significantly lower threshold for K+-induced contractions in human cerebral arteries may be of importance, especially in human cerebral ischaemic events.     

Optimal heparin surface concentration and antithrombin binding capacity as evaluated with human non-anticoagulated blood in vitro

Contact between blood and a biomaterial surface takes place in many applications and is known to activate the coagulation and complement systems. Heparin surface coatings have been shown to reduce blood activation upon contact with artificial surfaces. To establish the optimal heparin surface concentration, blood was incubated in a tubing loop model at 37 degrees C. The tubing was coated with different surface concentrations of heparin and rotated at three different velocities. We demonstrate that the blood compatibility of a surface with regard to coagulation, complement, and platelet activation can be improved by increasing the heparin surface concentration in the 6-12 pmol antithrombin/cm2 concentration interval. The binding of factor H is not influenced by the increased heparin surface concentration, suggesting that this factor is not the primary regulator of complement on heparin surfaces. In addition, the heparin coating has no effect on the complement activation that occurs on gas surfaces in extracorporeal circuits.     

Diurnal variations of serum erythropoietin at sea level and altitude

This study tested the hypothesis that the diurnal variations of serum-erythropoietin concentration (serum-EPO) observed in normoxia also exist in hypoxia. The study also attempted to investigate the regulation of EPO production during sustained hypoxia. Nine subjects were investigated at sea level and during 4 days at an altitude of 4350 m. Median sea level serum-EPO concentration was 6 (range 6–13) U·l^–1. Serum-EPO concentration increased after 18 and 42 h at altitude, [58 (range 39–240) and 54 (range 36–340) U·l^–1, respectively], and then decreased after 64 and 88 h at altitude [34 (range 18–290) and 31 (range 17–104) U·l^–1, respectively]. These changes of serum-EPO concentration were correlated to the changes in arterial blood oxygen saturation (r = –0.60,P = 0.0009), pH (r = 0.67,P = 0.003), and in-vivo venous blood oxygen half saturation tension (r = –0.68,P = 0.004) but not to the changes in 2, 3 diphosphoglycerate. After 64 h at altitude, six of the nine subjects had down-regulated their serum-EPO concentrations so that median values were three times above those at sea level. These six subjects had significant diurnal variations of serum-EPO concentration at sea level; the nadir occurred between 0800–1600 hours [6 (range 4–13) U·l^–1], and peak concentrations occurred at 0400 hours [9 (range 8–14) U·l^–1,P = 0.02]. After 64 h at altitude, the subjects had significant diurnal variations of serum-EPO concentration; the nadir occurred at 1600 hours [20 (range 16–26) U·l^–1], and peak concentrations occurred at 0400 hours [31 (range 20–38) U·l^–1,P = 0.02]. This study demonstrated diurnal variations of serum-EPO concentration in normoxia and hypoxia, with comparable time courses of median values. The results also suggested that EPO production at altitude is influenced by changes in pH and haemoglobin oxygen affinity.     

[H]Paroxetine binding in human platelets in relation to age and sex

The binding of [³H]paroxetine to serotonin uptake sites in human platelets from 47 individuals between 15 and 95 years of age was investigated. There were no significant age-related changes in maximal binding capacity (B_max) or apparent binding affinity (K_d). There were no significant differences in binding between males (n = 19) and females (n = 28).     

Use of Antibodies in Lymphocyte Secretions for Detection of Subclinical Tuberculosis Infection in Asymptomatic Contacts

We have previously demonstrated that Mycobacterium bovis BCG-specific immunoglobulin G antibodies in lymphocyte secretions (ALS) can be employed as a marker for active tuberculosis (TB). We aimed to determine whether the ALS method allows detection of subclinical TB infection in asymptomatic individuals. A prospective study of family contacts (FCs) of patients with active TB and healthy controls was performed. Thirteen of 42 FCs had high ALS responses, including 6 FCs who subsequently developed active TB. No correlation was observed between the tuberculin skin test and the ALS responses in the FCs (r = 0.1, P = 0.23). Among patients with active TB, BCG-specific ALS responses steadily declined from the time of diagnosis through 6 months following antimycobacterial chemotherapy (P = 0.001). The ALS assay enabled detection of infection in exposed symptom-free contacts, who are at greater risk for developing active TB. The method may also allow discrimination between effective treatment of active infection and suboptimal response to therapy.     

Plasma levels of somatostatin following a test meal in dogs. Initial atropine resistant vagally mediated decrease of somatostatin levels and increase of gastrin and insulin levels

Plasma levels of somatostatin like immunoreactivity (SLI), below referred to as somatostatin levels, were measured in peripheral plasma of conscious dogs. Basal somatostatin levels averaged 49 +/- 10 pM. Somatostatin as well as gastrin and insulin plasma levels were measured before and after feeding with and without prior atropinization. During the first 10 min after feeding somatostatin levels fell from 49 +/- 10 to 23 +/- 9 pM, whereas gastrin and insulin levels rose from 9 +/- 2 and 140 +/- 14 pM to 48 +/- 11 and 370 +/- 91 pM respectively. Atropine 0.01 or 0.1 mg/kg did not inhibit these responses. After the initial decrease, somatostatin level rose again and peaked at around 60 min after feeding (110 +/- 24 pM). This secondary rise was completely abolished by atropine in both doses tried. Gastrin and insulin levels remained elevated throughout the experiments with and without atropine. It is suggested that gastrin release and HCl secretion are inhibited by a tonic outflow of gastric somatostatin during basal conditions. The process of feeding induces an atropine resistant, vagally mediated decrease in somatostatin release from the gastrointestinal tract and this decreased output of somatostatin facilitates initiation of meal-related endocrine and exocrine gastric secretions.     

Amounts and distribution of intracellular magnesium and calcium in pancreatic beta-cells

beta-Cell-rich pancreatic islets were incubated for 60-120 min in the presence of 1 mM or 20 mM glucose and analysed with regard to their contents of magnesium and calcium and how these elements were distributed among subcellular fractions. The islets contained 42 mmol magnesium per kg protein with as much as 70 mmol per kg protein in the microsomal fraction. Both the total amount and intracellular distribution of magnesium remained unaffected after raising the glucose concentration of the incubation medium. The islet content of calcium was twice as high as that of magnesium, the mitochondria and secretory granules accounting for most of the calcium in the sedimentable fractions. In both organelles a substantial fraction of calcium was exchangeable as indicated from the incorporation of 45Ca during 90 min of incubation of the islets. When raising the glucose concentration to 20 mM the percentage exchange of calcium increased from 10 to 27 in the mitochondria and from 13 to 28 in the secretory granules. The glucose stimulation of 45Ca uptake was not associated with a statistically significant increase in the total amounts of calcium. However, in addition to stimulating calcium/calcium exchange, it cannot be excluded that glucose also induces a net accumulation of intracellular calcium in the beta-cells.     

Stimulation of murine B lymphocytes to IgG synthesis and secretion by the mitogens lipopolysaccharide and lipoprotein and its inhibition by anti-immunoglobulin antibodies.

The two mitogens, lipopolysaccharide (LPS) and lipoprotein (LP), both stimulate to an equal extent murine B lymphocytes to develop IgG-synthesizing and IgG-secreting cells. IgG synthesis and secretion was detected either by biosynthetic labeling of stimulated B cells, followed by immunoprecipitation and polyacrylamide gel electrophoresis of labeled Ig, or by the protein A plaque assay detecting all IgG-secreting cells with IgG-specific developing antisera. B cells from spleen, lymph node, thoracic duct and fetal liver of normal and T cell-deficient nu/nu mice are all stimulated by the two mitogens to develop IgG-secreting cells. Mitogen-induced IgG secretion, therefore, can occur independently of T cells and of external antigen. Anti-Ig antibodies inhibit the mitogen-induced development of Ig-secreting cells. Antibodies with specificities for μ chains when added before or soon after mitogenic stimulation of small, resting B cells, will inhibit these cells from developing into IgG-secreting cells. Later in culture, antibodies with specificities for γ chains also become inhibitory for the mitogen-induced development of IgG-secreting cells. These results indicate that the precursors of the IgG-secreting cells carry IgM in the outer surface membrane. They also suggest that during mitogen-stimulated growth of B cell clones, IgG becomes expressed in the surface membrane in a functional way which allows the inhibition of mitogen-induced IgG secretion by anti-γ antibodies.     

Leakage of macromolecules from guinea-pig tracheobronchial microcirculation. Effects of allergen, leukotrienes, tachykinins, and anti-asthma drugs

The tracheobronchial mucosa of anaesthetized guinea-pigs (normal or sensitized with ovalbumin to produce IgE and IgG antibodies) was superfused (0.02 ml min-1, 5 min) with saline, mediators, and (in sensitized animals) ovalbumin via a catheter atraumatically introduced orally. The intravascular blood pool and amount of macromolecules in excised trachea and adjoining main bronchi were quantified by measuring erythrocytes, that had been labelled in vivo with 99Tcm, and analysing for FITC-dextran, MW = 70,000, that had been given i.v. Extravasation of macromolecules was determined as the analysed total content minus the calculated intravascular content of FITC-dextran. Capsaicin 0.1 nmol extravasated 223 micrograms of FITC-dextran per g wet weight of airway tissue (P less than 0.001). Substance P 0.1 nmol, 41 micrograms g-1 (P greater than 0.05); substance P 0.3 nmol, 142 micrograms g-1 (P less than 0.001); eledoisine 0.1 nmol, 101 micrograms g-1 (P less than 0.01); ovalbumin 0.1 microgram, 179 micrograms g-1 (P less than 0.001); LTC4 0.2 pmol, 180 micrograms g-1 (P less than 0.001); LTD4 0.2 pmol 223 micrograms ml-1 (P less than 0.001). Bronchi and trachea were similarly affected by these agents. Prior superfusion (0.02 ml min-1, 30 min) with terbutaline 0.06 nmol, enprofylline 12 nmol, or lidocaine 6 nmol significantly reduced the effect of capsaicin. Enprofylline also reduced significantly the effect of LTC4. The degree of extravasation in this study was smaller than could be detected by changes in tissue wet to dry weight ratios. The present data support the view that tracheobronchial vascular permeability to macromolecules is subject to physiological and pharmacological control.