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Biomedical subjects

B A Peskar

Publications and source records attributed to B A Peskar.

At least 127 records · Page 7Linked to original sources
PubMed1987

The influence of irradiation on the biological half-life of prostacyclin in plasma of patients with gastrointestinal cancer.

In seven patients suffering from inoperable pancreatic cancer and in 14 patients with inoperable colonic cancer the half-life (T/2) of prostaglandin (PG)I2 in plasma in vitro has been determined before and at various intervals after irradiation. No significant difference of PGI2-T/2 could be observed either before irradiation, at the end of the irradiation period or 3 and 6 weeks after the last irradiation. Thus irradiation does not appear to interfere with the degradation of PGI2-T/2 in plasma. In patients with inoperable pancreatic and colonic cancer the PGI2-T/2 was not significantly different to that of the PGI2-T/2 of controls. Thus, a shortening of PGI2-T/2 is not a common feature in tumour patients. Hyperaggregation promoting seeding of metastases is not influenced by irradiation via the particular parameter of the PG-system.

Adult↗
PubMed1986

Radioimmunoassay for leukotriene E4. Use for determination of total sulfidopeptide-leukotriene release from rat gastric mucosa.

A conjugate of leukotriene (LT) E4 and bovine serum albumin (BSA) was prepared by covalently linking the free amino group of the hapten to the protein using dimethyl pimelindiimidate (DMP) as coupling reagent. Anti-LTE4 antibodies were raised in rabbits immunized with the conjugate. Binding of [3H]LTE4 to the antibodies is inhibited by 50% with 0.63 ng LTE4, while the relative cross-reaction of LTC4 and LTD4 is 46.3% and 12.6%, respectively. Using the radioimmunoassay release of sulfidopeptide-LT (SP-LT) from rat gastric mucosa incubated in vitro was determined after quantitative enzymatic conversion of SP-LT to LTE4. It could be demonstrated that this method is suitable for determination of SP-LT in biological material.

Amino Acids, Sulfur↗
PubMed1986

Leukotriene synthesis by human gastrointestinal tissues.

The prostaglandin and leukotriene synthesizing capacity of human gastrointestinal tissues obtained at surgery was investigated using radioimmunoassay for prostaglandin E2, leukotriene B4 and sulfidopeptide leukotrienes. The leukotriene immunoassay data were validated by high-pressure liquid chromatography (HPLC). During incubation at 37 degrees C, fragments of human gastric, jejuno-ileal and colonic mucosa released considerably larger amounts of prostaglandin E2 than of leukotriene B4 and sulfidopeptide leukotrienes. Gastrointestinal smooth muscle tissues released even larger amounts of prostaglandin E2, but smaller amounts of leukotrienes than the corresponding mucosal tissues. Adenocarcinoma tissue released larger amounts of leukotriene B4, sulfidopeptide leukotrienes and prostaglandin E2 than normal colonic mucosa. Ionophore A23187 (5 micrograms/ml) did not stimulate release of prostaglandin E2 from any of the tissues investigated, but enhanced release of leukotriene B4 and sulfidopeptide leukotrienes. HPLC analysis demonstrated that immunoreactive leukotriene B4 co-chromatographed almost exclusively with standard leukotriene B4, while immunoreactive sulfidopeptide leukotrienes consisted of a mixture of leukotrienes C4, D4 and E4. Leukotriene synthesis by human gastrointestinal tissues was inhibited by the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA) and the dual enzyme inhibitor BW755C (3-amino-1-(trifluoromethylphenyl)-2-pyrazoline hydrochloride). Synthesis of prostaglandin E2 was inhibited by the cyclooxygenase inhibitor indomethacin as well as by BW755C. Incubation of gastrointestinal tissues in the presence of glutathione decreased the amounts of leukotrienes D4 and E4, while release of leukotriene C4 was simultaneously increased. On the other hand, incubation of tritiated leukotriene C4 with incubation media from human gastric or colonic mucosa resulted in conversion of the substrate to [3H]leukotriene D4 and [3H]leukotriene E4. The results indicate the capacity of human gastrointestinal tissues to synthesize the 5-lipoxygenase-derived products of arachidonate metabolism, leukotriene B4 and sulfidopeptide leukotrienes, in addition to larger amounts of prostaglandin E2. Furthermore, considerable activities of the sulfidopeptide leukotriene-metabolizing enzymes gamma-glutamyl transpeptidase and dipeptidase were detected in human gastrointestinal tissues. These enzymes might play an important role in biological inactivation and/or change of biological profile of sulfidopeptide leukotrienes generated in the human gastrointestinal tract.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1986

[Leukotriene synthesis by gastrointestinal tissue and its pharmacologic modification].

Tissues of the gastrointestinal tract synthesize leukotriene (LT) B4 and the sulfidopeptide-leukotrienes LTC4, LTD4 and LTE4 from endogenous substrate. Formation of leukotrienes was demonstrated using radioimmunoassay, high pressure liquid chromatography (HPLC) and bioassay. Under basal conditions the gastrointestinal tissues released minor amounts of leukotrienes only. Formation of lipoxygenase-derived products of arachidonic acid metabolism was, however, significantly increased in the presence of various stimuli. Thus, significant amounts of LTB4 and of sulfidopeptide-leukotrienes were released from colonic and gastric mucosa of guinea-pigs sensitized against ovalbumin when incubations were carried out in the presence of antigen. Antigen-induced leukotriene formation was not found in the muscularis propria and subserosal of ovalbumin-sensitized guinea-pigs. Release of cyclooxygenase-derived metabolites of arachidonic acid, on the other hand, was most abundant in the subserosal layer of the guinea-pig colon and was not influenced by the immunological reaction. Inhibitors of cyclooxygenase, such as indomethacin, reduced gastrointestinal formation of prostaglandins, but not of leukotrienes. Inhibitors of 5-lipoxygenase, however, significantly decreased leukotriene formation. Synthesis of LTB4 and of sulfidopeptide-leukotrienes was also found in human colonic mucosal tissue, using the divalent cation-ionophore A23187 as stimulating agent. HPLC analysis demonstrated that the sulfidopeptide-leukotrienes released were composed of a mixture of LTC4, LTD4 and LTE4. In addition, human colonic mucosal tissue contained high activities of enzymes that rapidly convert LTC4 to LTE4. As in most biological systems LTE4 is less active than LTC4 and LTD4 degrading enzymes might represent a local inactivating mechanism. Mucosal tissue of patients with Crohn's disease synthesized considerably more LTB4 and sulfidopeptide-leukotrienes than non-inflamed mucosa.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Enhanced formation of sulfidopeptide-leukotrienes in ulcerative colitis and Crohn's disease: inhibition by sulfasalazine and 5-aminosalicylic acid.

Release of sulfidopeptide (SP)-leukotrienes (LT) in vitro from normal human colonic mucosa and from mucosal tissue obtained from patients with Crohn's disease (CD) and ulcerative colitis (UC) was investigated. It was found that inflamed mucosal tissue released significantly more SP-LT than normal colonic mucosa both under control conditions and after addition of calcium ionophore A23187. These results indicate the presence of endogenous stimuli as well as an increased responsiveness to an exogenous stimulus of LT formation in the inflamed mucosa. Sulfasalazine (SASP), a drug used in inflammatory bowel diseases, and its active metabolite 5-aminosalicylic acid (5-ASA) were found to inhibit colonic mucosal SP-LT formation, while only 5-ASA inhibited simultaneously synthesis of another arachidonic acid-derived inflammatory mediator, prostaglandin (PG) E2. The results suggest that SP-LT might be important mediators of inflammation in CD and UC.

Aminosalicylic Acids↗
PubMed1986

Ethanol stimulates formation of leukotriene C4 in rat gastric mucosa.

Ethanol-induced gastric mucosal damage is characterized by microcirculatory changes such as stasis and plasma leakage. Sluggish blood flow and stasis have also been observed after administration of exogenous leukotriene (LT) C4. The effect of ethanol on the release of LTC4 from rat gastric mucosa was therefore investigated. It was found that intragastric instillation of ethanol increases gastric mucosal release of LTC4 in a dose- and time-dependent manner parallel to the production of gastric lesions. The lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA) and the anti-ulcer drug carbenoxolone (CX) inhibited mucosal release of LTC4 and simultaneously protected against gastric damage caused by ethanol. It is concluded that increased formation of LTC4 and/or other 5-lipoxygenase-derived products of arachidonate metabolism may be involved in ethanol-induced gastric damage. Furthermore, inhibition of the 5-lipoxygenase pathway may be an important mechanism of action of gastric protective drugs.

Animals↗
PubMed1986

Prostacyclin synthesis stimulating plasma factor in patients with primary hyperlipoproteinemia--effect of dietary and drug treatment.

Recent data have demonstrated a possible pathogenetic influence of the prostacyclin synthesis stimulating plasma factor (PF) in various diseases. Studying this PF in 26 patients with primary hyperlipoproteinemia (HLP) we examined patients suffering from types IIa (n = 8), IIb (n = 6) and IV (n = 12) classified according to Fredrickson. Plasma was withdrawn at the detection of the HLP, 4 weeks after a dietary intervention and again 4 weeks after the beginning of a drug treatment. Using various test models such as rat and minipig aortic tissue, human aorta and saphenous vein as well as cultured endothelial and smooth muscle cells, the data reveal an in part significant improvement of PF running parallel with the improvement of HLP. These findings suggest that even though a significant difference between healthy controls and patients suffering from severe atherosclerosis has not been found, there occurs a significant improvement of PF in hyperlipidemic patients after successful treatment. Thus, it can be concluded that normalization of PF is one of the many factors improving the hemostatic balance in patients undergoing beneficial dietary or drug treatment.

Adult↗
PubMed1986

Biological half-life of prostacyclin and 6-oxo-PGF1 alpha levels in plasma of patients with colonic cancer.

Prostaglandins have been shown to play a central role in the formation of cancer. The synthesis of prostacyclin and its bioavailability may be an important local determinant for metastasis. As the amount of the biologically active substance is dependent in part on the half-life (T/2) we examined the question as to whether the T/2 of prostaglandin I2 (PGI2) is altered in patients suffering from colonic cancer at various stages of the disease. In addition, the influence of various therapeutic regimens was investigated. In 58 patients with various stages of colonic cancer no significant difference in PGI2-T/2 could be detected. No significant difference could be found before (10, 11 +/- 1, 9 min) and after (10, 03 +/- 1, 8 min) tumor resection, before (9, 89 +/- 1, 5 min) and after 10, 35 +/- 1,8 min) chemotherapy, before (10, 36 +/- 1, 5 min) and after (10, 89 +/- 2, 31 min) irradiation as well as before (8, 86 +/- 1, 9 min) and after (9, 07 +/- 1, 2 min) tumor resection at least 4 to 6 years ago. In 14 healthy people PGI2-T/2 (10, 05 +/- 2, 1 min) did not differ significantly. In all the 58 patients the plasma levels of 6-oxo-PGF1 alpha, the stable derivative of PGI2 were measured. As compared to healthy controls (less than 1 pg/ml) the actual 6-oxo-PGF1 alpha values of patients with colonic cancer were significantly increased. However, no correlation to the T/2 of PGI2 (r between 0, 03 and 0, 21, n.s.) in plasma in vitro could be discovered. After curative tumor resection and after chemotherapy the plasma levels of 6-oxo-PGF1 alpha were significantly lower than before. The data suggest that in patients suffering from colonic cancer the speed of degradation of PGI2 is not a key determinant in local hemostatic dysregulation favouring early metastasis. However, PGI2 or its stable derivatives may be involved in the development of colonic cancer.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Degradation of prostacyclin in the plasma of patients with terminal liver insufficiency.

It has been suggested earlier that the increased bleeding tendency observed in patients with hepatic coma is due to prostaglandin I2. Various experimental studies have reported an increased prostaglandin I2-formation, an enhanced plasma factor activity and a prolonged synthesis in-vitro. However, the rate of degradation of prostaglandin I2 in plasma could be another determinant alterating the locally available biologically active substance but this has not been examined so far. Thus, we examined the half-life of synthetic prostaglandin I in-vitro in plasma from 25 patients with terminal liver insufficiency in different stages of hepatic coma. In 8 healthy volunteers a 6 months follow up showed no significant change. The half-life of prostaglandin I in controls was 10.21 +/- 2.70 minutes, no different from coma stage I (10.16 +/- 1.36 minutes), coma stage II (10.86 +/- 2.24 minutes), coma stage III (10.95 +/- 3.06 minutes) or coma stage IV (12.07 +/- 2.88 minutes). However, a modest trend towards a prolongation and an increase in standard deviation with the coma stage can be noted. No influence of various drugs commonly used in these patients could be seen. It can thus be concluded that there is no important difference in degradation speed of prostaglandin I2 in the plasma of patients with terminal liver insufficiency, which could account for the increased bleeding tendency.

Adult↗
PubMed1986

Prostacyclin synthesis stimulating plasma factor in coronary heart disease.

Evidence has been presented that the prostacyclin synthesis stimulating plasma factor might be altered under various clinical conditions and thereby influence in a positive or negative way the hemostatic balance. Therefore, we studied angiographically verified coronary heart disease patients with a combination of various risk factors. Different test systems like cultured endothelial and smooth muscle cells, rat aorta, human coronary artery, minipig abdominal aorta and aorta of streptozotocin-induced diabetic rat have been used. With an increasing number of risk factors being present, the plasma factor activity shows a trend towards a decrease, however, in none of the groups was the difference statistically significant. It is thus concluded that changes in plasma factor activity are too small to be of clinical importance by influencing hemostatic regulation in humans.

Animals↗
PubMed1986

Immunohistochemical detection of 6-oxo-PGF1 alpha and PGE2 in radicular cysts.

Prostaglandin synthesis in the wall of radicular cysts was determined by immunohistochemistry and radiothinlayer chromatography. PGE2 is predominantly produced by plasma cells and histiocytic elements, whereas much less is synthesized by fibroblasts and endothelial cells as estimated using immunohistochemistry. 6-oxo-PGF1 alpha, however, was primarily found to be generated by endothelial cells and fibroblasts; only small amounts seem to be derived from histiocytic elements and plasma cells. The response of the cystic epithelium to anti-PGE2 and anti-6-oxo-PGF1 alpha antibodies was negative or showed only minimal staining. It can thus be concluded that the granulation tissue and its cellular components modulating the inflammatory process are the main source of prostaglandin synthesis in the wall of radicular cysts and may therefore be responsible for the resultant osteolytic activity.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Skin levels of arachidonic acid-derived inflammatory mediators and histamine in atopic dermatitis and psoriasis.

Since the biochemical events leading to cutaneous inflammation in atopic dermatitis and psoriasis are unknown, we studied the levels of arachidonic acid-derived mediators of inflammation as well as histamine in the suction blister fluid obtained from lesional and nonlesional skin of patients with these dermatoses. Mediator levels were determined radioimmunologically. Skin from healthy controls and uninvolved skin from patients contained very low or unmeasurable levels of the 5-lipoxygenase metabolite of arachidonic acid, leukotriene (LT) B4. In contrast, higher levels of LTB4-like immunoreactivity were detected in suction blister fluid from lesional atopic dermatitis skin, and even higher concentrations occurred in psoriasis lesions. LTB4-like immunoreactivity from atopic dermatitis suction blister fluid cochromatographed on reverse-phase high-pressure liquid chromatography with authentic LTB4, thus excluding cross-reaction of the LTB4-antibody with arachidonic acid or monohydroxyeicosatetraenoic acids. In contrast, suction blister concentrations of the cyclooxygenase metabolite of arachidonic acid prostaglandin (PG) E2 showed no significant differences between lesional and nonlesional patient skin and healthy control skin. PGD2 determined as a stable metabolite could not be detected in these samples. Histamine concentrations in lesional skin were within normal range. The elevated levels of the potent proinflammatory and immunomodulating mediator LTB4 could be involved in the pathogenesis of cutaneous inflammation in atopic dermatitis and psoriasis. In addition, they might explain the therapeutic efficiency of glucocorticosteroids, which among other actions inhibit the release of arachidonic acid from phospholipid stores by blocking the enzyme phospholipase A2. However, the specificity of disease expression in atopic dermatitis and psoriasis must be due to factors other than cutaneous LTB4 elevation.

Adolescent↗
PubMed1986

Platelet half-life, plasma thromboxane B2 and circulating endothelial-cells in peripheral vascular disease.

We studied platelet half-life (T/2), plasma thromboxane B2-levels (TXB2) and circulating endothelial cells in 107 patients with a mean age of 63 +/- 6.8 years and angiographically proven peripheral vascular disease (PVD). Patients were divided into 4 groups according to Fontaine but also according to additional clinical manifestations of atherosclerosis like coronary heart disease (CHD) and cerebrovascular disease (CVD). Furthermore, the influence of sex and smoking was investigated. Compared to patients without atherosclerotic manifestations we could detect an enhanced platelet consumption measured as shortened platelet half-life time (79.2 +/- 9.1 vs 100.9 +/- 5.6 hours, p less than 0.001 and an increased platelet activity measured as increased TXB2-plasma levels (51.6 +/- 20.9 vs 23.2 +/- 11.2 ng/ml, p less than 0.001). Correspondingly, the amount of circulating endothelial cells was increased 45.2 +/- 25.7 vs 20.3 +/- 23.4, p less than 0.001). Patients with PVD who smoked had the shortest actual platelet half-life, the highest TXB2 plasma levels and the greatest amount of circulating endothelial cells compared to non-smoking patients and controls. Patients with clinical stage IV according to Fontaine had the shortest platelet half-life, the highest TXB2 plasma levels and the greatest amount of circulating endothelial cells compared to the other clinical stages. Analyzing the influence of additional clinical manifestations of atherosclerosis we could detect only in patients with PVD and CHD significant differences compared to the other groups.

Adult↗