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Biomedical subjects

T Strasser

Publications and source records attributed to T Strasser.

At least 37 records · Page 2Linked to original sources
PubMed1990

Leukotriene B4 is involved in hemodialysis-associated neutropenia.

Biosynthesis of leukotriene B4 (LTB4) was studied in ten patients with end-stage renal failure undergoing chronic hemodialysis with a cuprophane membrane. As compared to healthy subjects the low basal plasma levels of LTB4 quantified by radioimmunoassay after extraction and purification by HPLC showed no significant difference. The time-course of LTB4 release after contact of the blood with the dialysis membrane without further in vitro stimulation was characterized by a rapid increase by about 500% within the first 10 min, appearing approximately at the same time as the known fall of white blood cell count which reaches its nadir after 20 min. Analysis of further release showed a decline of LTB4 biosynthesis to basal levels at the end of hemodialysis. These results indicate that activation of the 5-lipoxygenase pathway is involved in hemodialysis-associated leukopenia and may contribute to the alterations in neutrophils of patients with chronic dialysis therapy.

Arachidonate 5-Lipoxygenase↗
PubMed1990

Induction of leukotriene B4 formation by dialyzer membranes.

Interactions between blood and dialysis membranes lead to activation of the 5-lipoxygenase pathway of the arachiodonic acid metabolism during hemodialysis. Newly generated leukotriene B4 (LTB4) may contribute to the multifaceted granulocyte abnormalities of uremic patients.

Aged↗
PubMed1989

Prostaglandin E2 in the lung lavage fluid of premature newborns before and after surgical or medical closure of a patent ductus arteriosus.

To analyze the role of prostaglandin E2 in maintaining ductal patency in premature newborns, we measured the PGE2 concentration in the lung lavage fluid of nine patients within 24 h before and 4-8 h after surgical ligation of a patent ductus arteriosus and in two patients before and after closure of the ductus following intravenous indomethacin. The concentration of PGE2 ranged from 240 to 3770 pg/ml (mean 1666 +/- 1256 pg/ml) before operative intervention and show a significant decrease to 0-300 pg/ml (mean 93 +/- 106 pg/ml, P less than 0.001, Student's two-tailed t-test) within a few hours after ligation of the ductus arteriosus. The same significant decrease could be seen in two patients with successful indomethacin therapy (0.25 mg/kg in three doses/day) with concomitant ductus closure. In contrast, when indomethacin was given in a reduced dose (0.1 mg/kg in three doses/day), only a slight effect on PGE2 synthesis could be seen without closure of ductus arteriosus. We suggest that the fall of PGE2 levels in lung lavage fluid reflects the local synthesis in the ductus arteriosus itself and is responsible for the decrease induced by surgical ligation or pharmacological inhibition by indomethacin.

Bronchoalveolar Lavage Fluid↗
PubMed1989

[Blood pressure values during an exercise test].

High blood pressure readings are relatively frequent during dynamic exercise testing. However, because of the paucity of date concerning normal blood pressure values during exertion and the prognostic significance of exertion hypertension, the attitude to be adopted towards such patients is ill-defined. The present study proposes mean values for BP at a given workload, per age group (less than 20, 20-39, 40-59, greater than 60) and per sex. These values were computed from measurements during dynamic exercise tests performed by 303 subjects (177 male, 126 female) at 100 and 150 watts workloads. Systolic and diastolic pressures during exertion correlated positively with resting blood pressure values (p less than 0.001) and increased with age (p less than 0.001). Hypertension during exertion was defined as values more than 2 SD above mean values for the corresponding age group and sex. 20 subjects met these criteria in our study.

Adaptation, Physiological↗
PubMed1989

Supplementation with n-3 fatty acids from fish oil in chronic inflammatory bowel disease--a randomized, placebo-controlled, double-blind cross-over trial.

Thirty-nine patients with chronic inflammatory bowel disease were studied in a 7-month, double-blind, placebo controlled cross-over trial of dietary supplementation with fish oil, which provided about 3.2 g n-3 fatty acids per day. At control, biopsies from inflamed mucosa contained higher levels of arachidonic acid than uninvolved mucosa. Dietary n-3 fatty acids were well tolerated and incorporated into plasma and enteric mucosa phospholipids at the expense of n-6 fatty acids. The arachidonic acid-derived prostanoid generation was reduced by fish oil and the extension and severity of macroscopic bowel involvement was moderately improved. In patients with Crohn's disease, clinical activity was unchanged by fish-oil supplementation. In patients with ulcerative colitis, clinical disease activity fell during fish oil supplementation and thereafter; this was not significant however. Despite a moderate reduction in inflammatory lipid mediators by dietary n-3 fatty acids and limited morphological improvement in chronic inflammatory bowel disease, the clinical benefit seems to be confined to patients with ulcerative colitis.

Adult↗
PubMed1988

Anti-asthmatic effects of onions. Alk(en)ylsulfinothioic acid alk(en)yl-esters inhibit histamine release, leukotriene and thromboxane biosynthesis in vitro and counteract PAF and allergen-induced bronchial obstruction in vivo.

Five alk(en)ylsulfinothioic acid alk(en)yl-esters isolated from onions and four synthetic thiosulfinates inhibited 5-lipoxygenase of porcine leucocytes, histamine release and leukotriene B4 and C4 biosynthesis of human polymorphonuclear leucocytes, thromboxane B2 biosynthesis by human platelets and allergen- and PAF-induced bronchial obstruction of guinea-pigs. The anti-asthmatic and anti-inflammatory effects of onions depend in part on the thiosulfinate moiety: (Formula: see text).

Allergens↗
PubMed1988

Alteration of monocyte function following major injury.

The macrophage exerts its stimulatory and regulatory functions within the specific immune response via the interleukin 1 (IL-1) and prostaglandin E2 (PGE2), respectively. In a screening study of macrophage-related variables following injury, a total of 58 patients (mean age, 32 years; mean injury Severity Score, 38), macrophagic phenotyping with the monoclonal antibody Leu M3 and serial measuring of the antagonistic monokines IL-1 and PGE2 and of the macrophage-activating lymphokine interferon gamma were carried out on posttrauma days 0, 1, 3, 5, 7, 10, 14, and 21. The posttraumatic course was characterized by significant monocytosis, showing a peak value of 32% of Leu M3-positive cells compared with 15% of these cells in normal control subjects. During the posttrauma course, the macrophagic PGE2 output was significantly elevated up to eightfold on days 5 and 7 compared with that of control subjects (0.441 +/- 0.14 ng/mL vs 0.052 +/- 0.01 ng/mL). Conversely, macrophagic IL-1 synthesis was significantly suppressed until day 10. Levels of interferon gamma were suppressed to a significant degree during the two-day observation period, with a trend to slow recovery at the end of week 3. These data suggest that a negative regulatory macrophagic function may be the event initiating posttraumatic immunosuppression. To restore impaired macrophagic T-helper cell interaction, cyclo-oxygenase inhibition and substitution of interferon gamma may be useful to potentiate facilitatory macrophagic function and to block inhibitory macrophagic activity.

Adolescent↗
PubMed1988

Effects of interventions on community awareness and treatment of hypertension: results of a WHO study.

A WHO-coordinated study of the community control of hypertension in six countries (Cuba, Finland, France, Italy, Mongolia and Portugal) has shown that a comprehensive approach clearly improves the care of hypertensives in various populations. Hypertension control programmes were individually designed in each country and were implemented in defined communities. The intervention strategies varied between countries, the major components being: establishment of hypertension clinics and hypertension registers, involvement of health care personnel, and health education of the entire community. As a result of this programme, the blood pressure in the age group 30-59 years decreased on average by 3/2 mmHg among men and by 6/3.5 mmHg among women; the mean blood pressure level decreased twice as much in hypertensive subjects as in the entire population in the intervention areas of the study.

Adult↗
PubMed1987

Differences in arachidonic acid release, metabolism and leukotriene B4 synthesis in human polymorphonuclear leukocytes activated by different stimuli.

Products of the 5-lipoxygenase pathway were analyzed after different stimuli in human polymorphonuclear leukocytes prelabeled with 3H-arachidonic acid. Upon stimulation with the Ca2+ ionophore, A23187, polymorphonuclear leukocytes generate 118.2 +/- 18 pg [3H]dihydroxyeicosatetraenoic acids (diHETEs, including 3H-leukotriene B4 and its 6-trans-stereoisomers), after exposure to serum coated zymosan (35.8 +/- 9 pg) and N-fMet-Leu-Phe (39.5 +/- 9 pg). Conversion of 3H-arachidonic acid paralleled its release after A23187 and fMet-Leu-Phe exposure leaving only 13.8 +/- 7% and 13.6 +/- 3% of the released 3H-arachidonic acid unmetabolized, respectively. In contrast, after stimulation with serum-coated zymosan only a small fraction of the released 3H-arachidonate was converted to 5-lipoxygenase products leaving 73.0 +/- 5% of the released 3H-arachidonic acid unmetabolized. In parallel, leukotriene B4 synthesis was studied in unlabeled polymorphonuclear leukocytes, resulting in 40 +/- 15 ng upon A23187 stimulation, 4 +/- 0.9 ng upon stimulation with fMet-Leu-Phe and 1.8 +/- 0.9 ng after serum-coated zymosan, showing a different ratio of leukotriene B4 to 3H-diHETE for A23187 in contrast to serum-coated zymosan and fMet-Leu-Phe. These results indicate that the coupling between the release of the precursor fatty acid and the metabolism via the 5-lipoxygenase pathway differs greatly between different stimuli.

Arachidonic Acids↗
PubMed1987

Prostaglandin E2 (PGE2)-dependent suppression of interleukin alpha (IL-2) production in patients with major trauma.

The depression of interleukin-2 synthesis represents a major dysfunction within the cascade of immunologic defects induced by mechanical and thermal trauma. This study was undertaken to elucidate the negative control mechanisms that were responsible for the deficiency of IL-2 production in polytraumatized patients. Peripheral blood mononuclear cells (PBMC's) from 29 patients (average age, 35.8 years; average ISS, 35) were separated on post-trauma days 1, 3, 5, 7, 10, 14, and 21 and cultured as untreated cells (C), cells treated with indomethacin (C + INDO), and cells depleted of adherent cells (C-AC). Cell cultures were assayed for proliferative responses to PHA, IL-2 synthesis, PGE2 production, gamma-interferon levels, and phenotyping studies. On all days post-trauma there was found a marked reduction of IL-2 production compared to controls with a highly significant nadir from day 5 to day 10 with an almost 80% inhibition of IL-2 (p less than 0.005). C + INDO cells showed increases of IL-2 synthesis over untreated cells ranging from 48% (Day 1) to 220% (Day 7). Removal of adherent cells (C-AC) did not reverse the suppression of IL-2 production. gamma-interferon levels were depressed in parallel with IL-2 levels but did not increase with C + INDO. The phenotyping of the PBMC's showed highly significant suppression of OKT3+, OKT4+, and IL-2R+ lymphocytes as well as a highly significant elevation of the monocyte (p less than 0.005) count. There was a highly significant increase of PGE2 synthesis from monocytes, due to the monocytosis and to a higher capacity of synthesis of the individual cells following trauma. PGE2 levels peaked on Day 5 and 7 post-trauma at 400% of control (p less than 0.005). These data suggest that the suppression of IL-2 synthesis post trauma is caused mainly by two factors: the excessive PGE2 output of inhibitory monocytes and inadequate function in immature and/or blocked lymphocytes. The partial restoration of IL-2 synthesis by indomethacin suggests that blockade of the cyclo-oxygenase pathway as an immunomodulating therapy may reverse some of the immunologic abnormalities in multiple trauma patients.

Adult↗
PubMed1987

Effect of aldosterone on sodium and potassium concentrations in human mononuclear leukocytes.

The in vitro effect of aldosterone on intracellular sodium and potassium concentration was investigated in human mononuclear leukocytes (HML). HML were separated from blood by a Percoll gradient and intracellular Na+ and K+ were determined before and after incubation for 1 h at 37 degrees C. The intracellular (ic) Na+ and K+ concentrations after separation of HML were 17 +/- 5 and 59 +/- 18 mmol/kg wet cells (mean +/- SD, n = 6), respectively. In the absence of aldosterone the ic Na+ concentration decreased to 12 +/- 4, whereas the ic Na+ concentration remained constant at 18 +/- 8 mmol/kg wet cells when aldosterone (1.4 nM) was added to the incubation medium. In parallel, the ic K+ concentration decreased without added aldosterone but remained constant with aldosterone. The effect of aldosterone on the ic Na+ and K+ concentrations of HML was blocked by the aldosterone antagonist canrenone (140 nM). Cortisol at a physiological concentration (40 nM) did not alter ic Na and K concentrations in these cells. The results suggest that aldosterone binding to specific receptors in human mononuclear leukocytes significantly contributes to the regulation of monovalent cation levels in these cells. Thus, this easily accessible model of HML allows study of the effects of mineralocorticoids in relation to their receptors in intact cells in normal and pathological states.

Aldosterone↗
PubMed1987

Increased leukotriene B4 synthesis in patients with primary hyperparathyroidism is normalized after parathyroidectomy: a study comparing parathyroidectomy to thyroid adenomectomy.

Synthesis of leukotriene B4 (LTB4) upon stimulation of peripheral blood samples with the calcium ionophore A 23187 was studied in patients with primary hyperparathyroidism who underwent parathyroidectomy. Preoperatively, an increased LTB4 concentration of 1.76 +/- 0.19 ng/ml plasma was found, vs. 0.95 +/- 0.28 ng/ml in healthy individuals. On the fourth day after operation, the LTB4 concentration was almost normalized, reaching 1.25 +/- 0.23 ng/ml plasma. At the same time, mean serum calcium levels were reduced from 6.1 +/- 0.6 meq/liter before operation to 4.53 +/- 0.28 meq/liter after operation. In a control group, euthyroid patients with thyroid adenomas who underwent adenomectomy had normal LTB4 levels before operation (0.84 +/- 0.11 ng/ml) and did not show significant changes in LTB4-synthesizing capacity. The results indicate that synthesis of LTB4 in vivo may depend in part on factors related to serum calcium concentration or calcium metabolism.

Adenoma↗