Kurt Bergström

Effects of somatostatin on hepatic bile formation

Somatostatin is a peptide that has anticholeretic properties in the dog. The purpose of the present work was to investigate if somatostatin is an anticholeretic agent in humans also. The effects of intravenous infusion of somatostatin on hepatic bile flow and biliary electrolytes and secretion of biliary lipids were studied in 7 patients with complete biliary drainage who had been operated on for choledocholithiasis. Somatostatin, 250 microgram/h, was found to decrease the hepatic bile secretion by approximately 30%. The peptide also reduced the outputs of bile acids, cholesterol, and phospholipids and the outputs of sodium, potassium, and chloride. The concentrations of the biliary lipids were not significantly changed. Somatostatin inhibited the erythritol clearance in the 2 patients studied by approximately 25%. The present study thus provides evidence that somatostatin inhibits bile formation in humans. It appears as if the reduction in bile production is mainly due to decreased canalicular bile flow. It is possible that this effect of somatostatin is attributable to inhibition of bile acid synthesis or of transport-secretion of bile acids, or both.

IL‐8 and TNF‐α from peripheral neutrophils and acute‐phase proteins in periodontitis

OBJECTIVE In other studies, we have found deviant functions in peripheral neutrophils in periodontitis. The aim here was to study (1) the release of cytokines, IL-8 and TNFalpha, from neutrophils in 15 treated periodontitis patients and pair-matched controls as well as (2) the effects of cigarette smoking. MATERIAL AND METHODS Cytokines released in the incubation medium from un-stimulated and Fcgamma-R-stimulated neutrophils and some acute-phase reactants were measured with ELISA. RESULTS Non-smoking patients had trends for lower TNFalpha release compared to non-smoking controls, while corresponding trends were rather similar for Il-8. Smoking had a moderate but inconsistent effect on the release of both cytokines. However, in patients, the ratio between stimulated/un-stimulated release of Il-8 was significantly lowered by smoking (p<0.03). The parameters of inflammation in plasma differed only slightly between patients and controls, indicating that periodontal disease in a quiet phase has a negligible systemic effect with the possible exception for a higher IL-8 level. In contrast, smoking had significant systemic effect on the neutrophil count and IgG levels. CONCLUSIONS Release of IL-8 and TNF-alpha from peripheral neutrophils and various parameters of inflammation in plasma seem to be affected more by cigarette smoking than periodontal disease.

Neutrophil-related host response in hidradenitis suppurativa: a pilot study in patients with inactive disease.

Host-defence defects in hidradenitis suppurativa patients have been suspected, but not proven. Activated neutrophils can destroy the surrounding tissues by a release of reactive oxygen species and active proteases. Peripheral neutrophils from 15 female patients (mean age 46, range 27-57 years) in an inactive state of their hidradenitis suppurativa, were studied and compared with 15 age-matched healthy female controls. There were no significant differences between patients and controls in the assessments of intracellular elastase activity, total content of antigenic elastase or release of elastase. Furthermore, no differences were found in total content and membrane expression of the receptors measured. The generation of free oxygen radicals, after stimulation with the protein kinase C activator phorbol myristate acetate, was significantly higher in the patients than in the controls, while there was no difference after Fc-receptor-mediated stimulation. Dysfunctional neutrophils might be involved in the pathogenesis of hidradenitis suppurativa, but the findings should be interpreted with caution because of the small number of observed cases.

Chemiluminescent immunosorbent assay of serum myoglobin based on the luminol reaction

A simple and sensitive method for the determination of serum myoglobin is described. Myoglobin was determined in the range of 10-500 micrograms/1 by the chemiluminescent luminol reaction after adsorption to anti-myoglobin IgG onto a solid phase. Only 50 microliter of serum has to be used and the luminescent immunoassay (LIA) has a better sensitivity and a wider linear range than the conventional radioimmunoassay (RIA). However, in its present form LIA has a higher imprecision than RIA. In clinical specimens the correlation between the two methods was excellent.

Priming of neutrophils with tumor necrosis factor-α measured as Fcγ receptor-mediated respiratory burst correlates with increased complement receptor 3 membrane density

Hyperactive or primed neutrophils which damage tissue via cytokines and membrane receptors may be implicated in the pathogenesis of inflammatory conditions. The purpose of this study was to elucidate the priming mechanism in neutrophils by assessing changes in membrane receptors and the FcγR-mediated respiratory burst, measured as chemiluminescence. Purified neutrophilic granulocytes from healthy volunteers were preincubated with recombinant human tumor necrosis factor-α. This had a priming effect, inqreasing both the Fcγ receptor-mediated luminol-enhanced chemiluminescence and the membrane expression of the C3bi receptor (CRB) (r=0.843). The membrane densities of FcγRII, FcγRIII, and CR1 were unaffected by tumor necrosis factor-α. The mechanism of increased chemiluminescence may involve redistribution of the Fcγ receptors and cooperation with upregulated CR3, facilitating crosslinking of the receptors. The experiments were performed in a buffer without divalent cations, since these increased the background activity and abolished the priming effect of tumor necrosis factor-α. In conclusion, a simultaneous increase in the FcγR-mediated respiratory burst and CR3 density after priming with tumor necrosis factor-α indicates a cooperation between FcγR and CR3.

A sensitive method for determination of serum hemoglobin based on iso-luminol chemiluminescence

A simple and rapid method for determination of serum hemoglobin is described. Hemoglobin may be determined in serum within the range of 0.02-400 mg/1 by the sensitive chemiluminescent iso-luminol reaction. The iso-luminol assay was considerably more sensitive than the conventional colorimetric procedure based on tetramethylbenzidine. Precision and accuracy were higher with the iso-luminol assay especially at low levels of hemoglobin. The correlation between the luminescent and colorimetric method was linear but the colorimetric determinations resulted in higher concentrations of hemoglobin. This discrepancy was probably caused by non-heme serum iron which interfered more strongly with the colorimetric method.

Peripheral neutrophils after allergic asthmatic reactions

The response of peripheral neutrophils was studied in 16 patients with allergic asthma after challenge with birch/grass pollen allergen, in order to identify inflammatory markers associated with only the early asthmatic reaction and those associated with both early and late asthmatic reactions. The allergen challenge proceeded until the patients had an early asthmatic reaction with 100% increase in specific airway resistance. Bronchoconstriction after allergen challenge was monitored hourly over 9 h and finally after 18 h, by measurement of the forced expiratory volume in 1 s. Seven patients had a late reaction, defined as a decrease in forced expiratory volume in 1 s of more than 15%. Blood samples were taken before and 18 h after challenge. After allergen challenge (18 h) the blood concentration of neutrophils in patients with a late asthmatic reaction was 1.4 times higher than before challenge and there was a tendency for increased Fcγ receptor-mediated chemiluminescence. Lewis X-antigen (CD 15), which is associated with endothelial adhesion and extravasation, significantly decreased at the same time. Neutrophils were incubated with the tetrapeptide arginine-glycine-aspartate-serine before and 18 h after allergen challenge. Both patient groups showed an increased Fcγ receptor-mediated chemiluminescence and a decreased Fcγ receptor membrane expression following allergen challenge, suggesting a preactivation. In conclusion, patients with a dual asthmatic reaction show a sustained primed inflammatory response and primed neutrophils compared with patients with only an early reaction when measured after the decline of clinical symptoms provoked by allergen challenge.

The effect of major surgery, low doses of heparin and thromboembolism on plasma antithrombin. Comparison of immediate thrombin inhibiting capacity and the antithrombin III content

Abstract Antithrombin in plasma was studied by two different methods in a group of patients undergoing major surgery and taking part in a double-blind investigation on low-dose heparin treatment. The AT III results (Mancini method) were only slightly affected by thromboembolism which is in agreement with earlier findings. The immediate thrombin inhibiting capacity using a chromogenic tripeptide as substrate was, however, found to increase in connection with thromboembolism. The fact that the low doses of heparin given to the patients have no effect on any of the antithrombin methods used and that clinical effect was achieved, suggests that the prophylactic effect may depend on inhibition of earlier stages in the development of thrombosis.

Streptokinase, but not tissue plasminogen activator, attenuates platelet aggregation in patients with acute myocardial infarction.

Abstract. Objectives. To investigate if tissue plasminogen activator (tPA) and streptokinase given during acute myocardial infarction (AMI) have different effects on platelet aggregation which could contribute to the higher reocclusion rate observed after tPA.

Fibrin (ogen)-derived peptide Bβ 30–43 is a sensitive marker of activated neutrophils during fibrinolytic-treated acute myocardial infarction in man

Neutrophils, elastase, the specifically elastase-derived fibrin split product, B beta 30-43, and C-reactive protein were determined in 30 consecutive patients with acute myocardial infarction. At admission to the coronary care unit 4.2 +/- 0.8 hours after the onset of symptoms, all elements were increased above the reference levels, while compared with convalescent levels, only neutrophils and B beta 30-43 were increased. After the streptokinase treatment, neutrophils, elastase, and B beta 30-43 increased abruptly and peaked (p less than 0.0001) within 1.5 hours. Plasma creatine kinase MB and C-reactive protein reached their peak levels after about 12 and 24 hours, respectively. Peak indices of neutrophils and creatine kinase correlated (r = 0.60, p less than 0.0006). Compared with the age-matched reference range, the convalescent level of B beta 30-43 was increased (p less than 0.0001). Of the tested elements suggestive of neutrophil activation, B beta 30-43 showed signs of being the most sensitive. In keeping with animal studies, neutrophils are activated early during the course of acute myocardial infarction and their activation seems to become accelerated by fibrinolytic treatment. Neutrophils may remain activated in the convalescent phase.