Acetylsalicylic Acid Treatment Research Articles

Do Non-Steroidal Anti-Inflammatory Drugs Influence the Steroid Hormone Milieu in Male Athletes?

Prostaglandins modulate the hypothalamus-pituitary-adrenal and -gonadal axis pathways. We explored the effects of a single course of treatment with acetylsalicylic acid (ASA), an inhibitor of prostaglandin synthesis, on the steroid milieu in athletes. Morning plasma cortisol (F), dehydroepiandrosterone sulphate, free-testosterone, testosterone (T) and their ratios were evaluated before and after the administration of either ASA or placebo in twelve male athletes, when affected by minor musculoskeletal trauma and, as control, after a five/six week wash-out in healthy conditions respectively. One tablet of ASA (800 mg), or placebo, was administered two times daily for 10 days during treatment. All the volunteers suspended exercise training during treatment. The results revealed that compared to placebo, plasma F was significantly lower after ASA treatment (p = 0.023). Furthermore, the comparison of hormone's absolute and percentage of variations (Delta and Delta%) between ASA and placebo treatment showed significant differences respectively for DeltaF (p = 0.045), for DeltaT (p = 0.047), for DeltaT/F (p = 0.042), for DeltaF% (p = 0.04) and for DeltaT% (p = 0.049). Our data suggest that in comparison to placebo, a short-term ASA treatment is able to influence the plasma steroid milieu in athletes. Due to the observed variability of the individual hormonal patterns, further research is required to substantiate these findings.

Involvement of Both Subgroups A and B of Expansin Genes in Kiwifruit Fruit Ripening

Two complementary DNA fragments encoding expansin genes Ad-EXP1 and Ad-EXP2 were isolated from ripening kiwifruit (Actinidia deliciosa cv. Bruno) by reverse transcription–polymerase chain reaction amplification using a pair of degenerate primers. The homology between these two expansin family members was 50% in nucleotide sequence and 74% in amino acid sequence. It was revealed that Ad-EXP1 and Ad-EXP2 belong to subgroups A and B of an expansin gene family respectively. However, gene expression of these two members shared similar patterns. Both were upregulated by ethylene treatment and downregulated by acetylsalicylic acid treatment. The study suggests that members of both subgroups A and B of the expansin family are involved in kiwifruit fruit ripening.

Single dose of acetylsalicylic acid in patients with Type 2 diabetes mellitus and/or chronic renal failure ameliorates anaemia by decreasing the rate of neocytolysis

Anaemia in diabetes mellitus (DM) and/or chronic renal failure (CRF) may be caused by a decreased production of erythropoietin (EPO), EPO resistance, and by the lysis of the young circulating red blood cells (neocytolysis) induced by subclinical inflammation and low EPO level. Aims of this study were to detect EPO resistance in patients with DM and/or CRF and to prove, that acetylsalicylic acid (ASA) is able to improve the haemopoietic status by decreasing neocytolysis. In a cross-sectional study, three groups of selected patients (patients with DM; patients with DM+CRF; patients with CRF without DM, n=15 each) and a group of controls (non-diabetic, nonazotemic subjects, n = 10) were compared. In the intervention part of the study, the effect of a single dose of 1 gram ASA on neocytolysis was investigated in a subgroup of these patients. Despite the similar EPO level (p = 1.000), all three patient groups had lower haemoglobin and haematocrit than control persons (p < 0.05 in all cases). Patients with DM+CRF had lower haemoglobin than patients with DM or CRF alone (p < 0.05). Single dose of ASA induced a fast increase in serum EPO level, a concomitant rise of the Rtc number and rate, red blood cell count, haematocrit and haemoglobin p < 0.01 for each). These changes were accompanied by a marked decrease in serum lactate dehydrogenase activity (p < 0.01). DM and CRF may induce erythropoietin resistance. In these patients, ASA treatment increases serum EPO level. The higher EPO level and the anti-inflammatory effect of ASA may decrease neocytolysis.

The platelet inhibiting effect of a clopidogrel bolus dose in patients on long-term acetylsalicylic acid treatment

Introduction Addition of clopidogrel to patients treated with ASA has been shown to decrease the incidence of in-stent thrombosis after percutaneous coronary interventions. However, it has also been reported that up to 30% of patients do not achieve adequate platelet inhibition from standard dosages of ASA and clopidogrel. There is a demand for reliable methods to measure the individual platelet inhibiting effect of this combination therapy. Materials and methods The primary aim of the present investigation was to compare three methods for evaluation of the platelet inhibiting effect of a clopidogrel bolus dose in patients on long-term acetylsalicylic acid treatment. Thirty patients presenting for coronary angiography/PCI were included. Two patients were excluded due to technical problems. All patients were on 75–100 mg ASA/day for at least 8 days. Blood samples were analysed before and 16 h after a 300 mg clopidogrel bolus dose. The platelet inhibiting effect was measured with (1) Whole blood flow cytometry (17 patients); (2) a bed-side test, Platelet Mapping™ assay for the thrombelastograph (28 patients); and (3) PFA (Platelet function analyser) − 100 (26 patients). Results With flow cytometry, the percentage of platelets expressing P-selectin ( p = 0.03) on their surface decreased significantly after the bolus dose of clopidogrel. There was also a reduction of platelets binding fibrinogen when stimulated with ADP. A significantly ( p = 0.002) increased platelet inhibition could also be demonstrated with Platelet Mapping™. PFA-100 could not measure any significant platelet inhibiting effect of clopidogrel. Conclusion A significant platelet inhibition could be demonstrated with flow cytometry and the Platelet Mapping™ assay, but not with PFA-100. However, levels of response for the individual patient with these three methods were inconsistent. Further studies are needed to evaluate how the results correlate to the clinical risk of thrombosis and bleeding.

Aspirin and statin medication decreases the risk of myocardial infarction associated with LTA and NFKBIL1 polymorphisms

Abstract Lymphotoxin-α (LTA) is a cytokine involved in inflammatory reactions. NFKBIL1 is a regulator of the NF-κB complex. The study investigated the associations of LTA 804 C&gt;A and NFKBIL1-63 T&gt;A polymorphisms with the use of statin and acetylsalicylic acid (ASA) treatment in relation to myocardial infarction (MI). The study population comprised of 600 Finnish individuals who underwent coronary angiography volunteering for the Angiography and Genes Study. Genotypes were detected by the TaqMan 5′ nuclease assay. We found a interaction between the LTA genotype (p=0.002) and the NFKBIL1 genotype (p=0.012) and statin treatment in relation to MI. Subjects with the LTA AA or the NFKBIL1 AA genotype were at a 2.77 (95% CI:1.22-6.24) and 2.85 (95% CI:1.22-6.66) times higher risk, respectively, of suffering an MI when compared to other genotypes among statin non-users. ASA treatment also modulated associations between LTA and NFKBIL1 genotypes and MI (p=0.015 and p=0.028 respectively). The NFKBIL1-A-LTA-A haplotype showed a 61% increase in the risk of MI compared to the NFKBIL1-T-LTA-C haplotype among statin non-users. Anti-inflammatory medication modifies the genotype-related risk of MI, suggesting that subjects with LTA and NFKBIL1 AA haplotype might especially benefit from the treatment.

Antioxidative enzyme and glutathione S-transferase activities in diabetic rats exposed to long-term ASA treatment

Low-dose acetylsalicylic acid (ASA) treatment is a standard therapeutic approach in diabetes mellitus for prevention of long-term vascular complications. The aim of the present work was to investigate the effect of long-term ASA administration in experimental diabetes on activities of some liver enzymes: glutathione peroxidase (GSHPx), catalase, glucose-6-phosphate dehydrogenase (G6PDH) and glutathione S-transferase (GST). Blood glucose, glycated hemoglobin, as well as plasma ALT and AST activities increased in rats with streptozotocin-induced experimental diabetes. The long-term hyperglycemia resulted in decreased activities of GSHPx (by 26%), catalase (by 34%), GST (by 38%) and G6PDH (by 27%) in diabetic animals. We did not observe increased accumulation of membrane lipid peroxidation products or altered levels of reduced glutathione in livers. The linear correlation between blood glucose and glycated hemoglobin in diabetic animals was distorted upon ASA treatment, which was likely due to a chemical competition between nonenzymatic protein glycosylation and protein acetylation. The long-term ASA administration partially reversed the decrease in GSHPx activity, but did not influence the activities of catalase and GST in diabetic rats. Otherwise, some decrease in these parameters was noted in ASA-treated nondiabetic animals. Increased ASA-induced G6PDH activity was recorded in both diabetic and nondiabetic rats. While both glycation due to diabetic hyperglycemia and ASA-mediated acetylation had very similar effects on the activities of all studied enzymes but G6PDH, we conclude that non-enzymatic modification by either glucose or ASA may be a common mechanism of the observed convergence.

Enhanced glucotropaeolin production in hairy root cultures of Tropaeolum majus L. by combining elicitation and precursor feeding

We have studied the effects of precursor amino acids (phenylalanine and cystein), elicitors (salicylic and acetylsalicylic acids, methyl jasmonate, β-aminobutyric acid, yeast extract), PAL-inhibitor (1-amino-2-phenylethylphosphonic acid) applied alone or in combination on glucotropaeolin production and myrosinase activity in hairy root cultures of Tropaeolum majus. Short, 24-h treatment, and subsequent transfer of hairy roots to the fresh medium enabled avoiding detrimental effect of studied stimulators on biomass growth. In control cultures the highest glucotropaeolin content, 58.1 ± 6.7 mg g−1 DW, was detected on the 3rd day after transfer of the roots to the fresh medium but glucotropaeolin yield (mg 100 ml–1 culture volume) had been increasing until the 9th day after transfer as a result of continuous biomass growth. Glucotropaeolin content and yield were 2-fold enhanced after treatment with precursor amino acids or PAL-inhibitor alone, but their combination additively led to 4-fold increase in glucotropaeolin production. Among the studied elicitors acetylsalicylic acid induced the highest, 3-fold increase in glucotropaeolin production, it also enhanced myrosinase activity, but to a smaller extend (by about 50%). Acetylsalicylic acid also potentiated induced by precursors, PAL-inhibitor, methyl jasmonate and yeast extract production of glucotropaeolin. The highest, 4.8-fold increase in glucotropaeolin production was found after combined acetylsalicylic acid and precursors treatment. Additive effect of acetylsalicylic acid-combined treatment on myrosinase activity was not detected. The obtained results indicate that amino acid precursors, phenylalanine and cystein, availability may be a limiting factor in the process of stimulation of glucotropaeolin production in T. majus hairy root cultures.

Usefulness of whole blood aggregometry and its comparison with thromboxane generation assay in monitoring acetylsalicylic acid effectiveness – a multiparametric study in rats

There is a need for consensus concerning universal methodological criteria for detection of suboptimal response to acetylsalicylic acid (ASA) therapy. Therefore, animal models to test for ASA effectiveness remain of interest. Our objective was to verify the usefulness of multiparametric whole-blood impedance aggregometry and thromboxane A(2) generation, which are the most popular techniques used for monitoring of ASA treatment effectiveness. Using multiparametric analysis of whole-blood impedance aggregometry, we examined which parameters of platelet aggregation or disaggregation allow for the best discrimination between ASA-treated (4 or 40 mg/kg for 60 days) and non-treated male rats. The effectiveness of ASA-mediated inhibition of platelet cyclooxygenase-1 was verified by determination of plasma thromboxane B(2) and urine 11-dehydro-thromboxane B(2), accepted as reference assays for monitoring of ASA-mediated platelet cyclooxygenase-1 inhibition. Two of the platelet agonists used, collagen (1 mg/L) and arachidonic acid (0.5 mmol/L), allowed discrimination of control and ASA-treated animals, whereas adenosine diphosphate (5 micromol/L) was not effective. It is noteworthy that only ASA-mediated changes in duration of the rising phase for platelet aggregation and the area under the curve for collagen-induced aggregation allowed significant discrimination between low and high ASA dose and remained correlated with the reference parameter, plasma thromboxane B(2). Analysis of aggregation curves, routinely based only on the amplitude and rate of platelet aggregation, may not be enough discriminative to distinguish between varying ASA doses and treatment schedules.

Physiological and Antioxidative Effects of Dietary Acetyl Salicylic Acid in Laying Japanese Quail (Coturnix japonica) under High Ambient Temperature

The objective of the present study was to determine if acetylsalicylic acid (ASA) would have further antioxidative effects beyond lowering rectal temperature of stressed laying Japanese quail and hence improve its physiological status. During summer season when daily high temperatures averaged between 33 and 36°C and relative humidity averaged between 60 to 70%, four treatment groups of adult Japanese quail each containing three replicates of fifteen females were fed either a control diet containing 0% ASA or the control diet supplemented with 0.025, 0.05 or 0.1% ASA from 8 to 16 wk of age. Rectal body temperature was significantly decreased by feeding 0.05 and 0.1% ASA. Hen-day egg production was significantly increased for quails fed the diet containing 0.05% and 0.1% ASA. Shell thickness seemed to be thicker at the higher levels of ASA. Serum T3 concentration was decreased significantly (P≤0.05) in quails fed 0.1% ASA (0.38ng/ml) in comparison with controls (0.62ng/ml), but serum T4 concentration was not significantly affected. Dietary ASA had a positive effect on humoral immunity and quails fed 0.05 and 0.1% ASA had a significantly higher total antibody titer compared to other treatments. ASA treatments caused a significant decrease in serum cholesterol, glucose and hepatic TBARS as an indicator for lipid peroxidation, as well as enhancement in the activity of antioxidative enzymes GSH-Px and SOD in a dose dependent manner. These antioxidative effects were accompanied with a significant reduction in corticosterone levels due to ASA treatments. Therefore, it could be concluded that feeding diets containing 0.05 or 0.1% ASA during the summer season could have potential benefits for poultry welfare and productivity because of reducing body temperature and oxidative stress, which consequently allowing more physiological resources to be used for responding to environmental stressors.

Nachbehandlung der pAVK nach Interventionen und Gefäßchirurgie mit Antikoagulanzien und Thrombozytenfunktionshemmern

Platelet inhibitors and anticoagulants are used in the longterm treatment after successful infrainguinal bypass grafts as well as endovascular revascularisation procedures. However, evidence of the usefulness of these therapies is limited with respect to efficiency (patency rate, mortality) and safety (bleeding tendency) concerning these indications. Sufficient data are only available for acetylsalicylic acid treatment after implantation of prosthetic bypass grafts, the data basis for the use of antithrombotic medication in venous bypass grafts or following successful balloon angioplasty with or without stent implantation is, however, inconclusive. The recommendation for lifelong therapy with acetylsalicylic acid after infrainguinal bypass surgery and endovascular treatment is based mainly on the concept of prophylactic treatment of manifest atherosclerotic disease.

Pretreatment of Acetylsalicylic Acid Promotes Tumor Necrosis Factor-related Apoptosis-inducing Ligand-induced Apoptosis by Down-regulating BCL-2 Gene Expression

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been shown to be selective in the induction of apoptosis in cancer cells with minimal toxicity to normal tissues. However, not all cancers are sensitive to TRAIL-mediated apoptosis. Thus, TRAIL-resistant cancer cells must be sensitized first to become responsive to TRAIL. In this study, we observed that pretreatment by acetylsalicylic acid (ASA) augmented TRAIL-induced apoptotic death in human prostate adenocarcinoma LNCaP and human colorectal carcinoma CX-1 cells. Western blot analysis showed that pretreatment of ASA followed by TRAIL treatment activated caspases (8, 9, and 3) and cleaved poly(ADP-ribose) polymerase, the hallmark feature of apoptosis. Most interestingly, at least 12 h of pretreatment with ASA was prerequisite for promoting TRAIL-induced apoptosis and was related to down-regulation of BCL-2. Biochemical analysis revealed that ASA inhibited NF-kappaB activity, which is known to regulate BCL-2 gene expression, by dephosphorylating IkappaB-alpha and inhibiting IKKbeta activity but not by affecting the HER-2/neu phosphatidylinositol 3-kinase-Akt signal pathway. Overexpression of BCL-2 suppressed the promotive effect of ASA on TRAIL-induced apoptosis and changes in mitochondrial membrane potential. Taken together, our studies suggested that ASA-promoted TRAIL cytotoxicity is mediated through down-regulating BCL-2 and by decreasing mitochondrial membrane potential.

Pregnancy in Essential Thrombocythemia: Experience With 40 Pregnancies

This retrospective study reviewed the course of 40 pregnancies in 16 women diagnosed as having essential thrombocythemia (ET). These women were seen at 5 hospitals in Finland in the years 1980-1995. In 10 women, thrombocytosis was identified for the first time during pregnancy. The mean age at the time ET was diagnosed was 27 years, and the median initial platelet count was 1082 x 10 9 /L. The median follow-up interval from the time of diagnosis was 6 years 6 months. Eighteen of the 40 pregnancies (45%) were complicated. Fifteen (38%) ended in miscarriage, all but 2 of them in the first trimester. Three pregnancies ending in a live birth were complicated by eclampsia or preeclampsia. In 7 women, all 11 pregnancies were uneventful. In the other 9 patients, 18 of 29 pregnancies (62%) were complicated. Only 11 of these pregnancies (38%) followed a normal course and had a good outcome. The most common complication, occurring in one third of pregnancies and comprising 72% of all complications, was spontaneous abortion. There were 2 intrauterine fetal deaths. The risk of complications did not appear to relate to either nonpregnancy-related symptoms of ET or to the platelet count before or during pregnancy. Fetal growth was normal in all but 1 of 25 second- or third-trimester pregnancies. Eleven of the 16 women had received treatment for ET. Most commonly, acetylsalicylic acid (ASA) was given in daily doses of 50 to 250 mg. Five patients were on interferon before pregnancy and 3 of them changed to ASA. Pregnancy-related complications occurred in 67% of pregnancies in untreated women. In contrast, none of 13 pregnancies in women treated before or during pregnancy were complicated. The live birth rate was 100% in treated cases and 44% without treatment, This study affirms an increased risk of pregnancy-related complications-particularly early spontaneous abortion-when the mother has ET. Low-dose ASA treatment appears to prevent complications.

Prostacyclin, Thromboxane A2, and the Effect of Low-Dose ASA in Pregnancies at High Risk for Hypertensive Disorders

In preeclampsia, underperfusion of the uteroplacental circulation and placental ischemia combine to damage the placenta. This in turn is thought to cause widespread endothelial cell damage and also an imbalance in eicosanoids, the vasodilator prostacyclin, and the vasoconstrictor thromboxane A2. Although low-dose acetylsalicylic acid (ASA) restores the balance in favor of prostacyclin, the clinical results of administering ASA remain uncertain. The present longitudinal study sought to find whether the prostanoids have a pathophysiological role in pregnancy-induced hypertension (PIH) and intrauterine growth restriction (IUGR). In addition, ASA was given in a daily dose of 0.5 mg/kg. Participants were 90 women at risk of preeclampsia or IUGR who had bilateral notching in the uterine arteries when screened by Doppler ultrasonography at 12 to 14 weeks gestation. After assigning these women to ASA or a placebo, 43 women in both groups were followed up throughout pregnancy. Urine samples were taken at baseline and at 24 to 26 weeks and 32 to 34 weeks of gestation, and analyzed for metabolites of thromboxane A2 and prostacyclin. ASA treatment significantly prevented PIH, especially before 37 weeks vacation, as well as preeclampsia, regardless of whether bilateral notches persisted. If bilateral notching disappeared by 24 to 26 weeks gestation, ASA-treated women less often had PIH and preeclampsia than did placebo recipients. ASA did not alter outcomes when bilateral notches persisted at 32 to 34 weeks gestation. When notches were absent at this time, ASA-treated women had lower rates of PIH and preeclampsia. When PIH developed before 37 gestational weeks, the ratio of prostacyclin metabolite to thromboxane A2 metabolite did not increase as much as in other pregnancies. In placebo patients with preeclampsia, levels of prostacyclin metabolite were significantly lower than in other pregnancies at 12 to 14 weeks gestation. In placebo recipients, the metabolite ratio did not change in the course of pregnancy and was not influenced by adverse outcomes. Metabolite ratios increased in ASA-treated women whether the outcome was normal or abnormal. These findings suggest that the balance between vasodilating and vasoconstricting prostanoids shifts in an unfavorable manner in pregnant women with PIH. Treatment with ASA may help to restore a normal balance. It is best given beginning early in pregnancy.

Cyclooxygenase-2 Inhibitors Attenuate Angiotensin II–Induced Oxidative Stress, Hypertension, and Cardiac Hypertrophy in Rats

Angiotensin II is an important oxidative stress mediator. Our previous studies have indicated that the potent antioxidative properties of acetylsalicylic acid play an important role in its cardiovascular protective effects. There are some ongoing controversies concerning the use of selective cyclooxygenase-2 inhibitors in cardiovascular disease. The aim of this study was to determine whether the cyclooxygenase-2 selective inhibitors rofecoxib and nimesulide possess antioxidative and cardiovascular protective effects against angiotensin II. Chronic subcutaneous angiotensin II infusion increased cardiovascular but not colonic tissue superoxide production, heart/body weight ratio, and blood pressure. Moreover, angiotensin II selectively increased cardiac cyclooxygenase-2 but not cyclooxygenase-1 expression, which was totally prevented by acetylsalicylic acid treatment. Similar to acetylsalicylic acid, rofecoxib or nimesulide treatments significantly attenuated angiotensin II-induced oxidative stress, hypertension, and cardiac NAD(P)H oxidase subunit p47(phox) expression. Rofecoxib also reduced cardiac hypertrophy. Treatment with nonselective anti-inflammatory drugs ibuprofen, indomethacin, or salicylic acid did not show any effect on angiotensin II-induced superoxide production, hypertension, or cardiac hypertrophy. Although acetylsalicylic acid and salicylic acid inhibited angiotensin II-induced nuclear factor kappaB (NF-kappaB) activation, nimesulide did not modify NF-kappaB activation. In conclusion, cyclooxygenase-2 pathway is implicated in angiotensin II-induced oxidative stress and deleterious cardiovascular changes. Rofecoxib and nimesulide produced significant antioxidative effect by reducing NAD(P)H oxidase-dependent superoxide generation. These effects seem to be independent of NF-kappaB inhibition.

Marked increase of fibrin gel permeability with very low dose ASA treatment

Previous data from our group show that acetylsalicylic acid (ASA), especially at low dose, alters the network structure of fibrin, rendering it more porous. The present study was performed to extend the dose-response curve for effects of ASA on fibrinogen clotting properties and to examine the variability of these effects during a 24-h dose interval. Fifteen healthy volunteers received ASA 37.5 mg daily (low dose) for 10 days and, after an interval of 2 weeks, 320 mg daily (medium dose) for 7 days, followed by a single bolus dose of 640 mg (high dose). The plasma fibrinogen concentrations were determined and the permeability of fibrin gels (Ks) was assayed with a recently modified flow measurement technique. Three-dimensional (3D) structure of the fibrin network was studied by confocal microscopy. ASA therapy did not influence fibrinogen concentrations. Compared to baseline, Ks levels were increased by 21% and 31% in samples during medium and high dose ASA treatment (p<0.01) and, even more markedly, by 44% (p<0.0001) with very low dose ASA treatment (p<0.01, compared to the higher doses). The effects of ASA on fibrin gel permeability were stable over a 24-h dose interval. During ASA treatment, thicker fibrin fibers and larger network pores with irregular structure were observed by confocal microscopy. Acetylation of lysine residues in the fibrinogen molecule may explain the alterations in its clotting property, resulting in altered fibrin gel permeability. The mechanism(s) behind the greater increase in fibrin gel permeability and alterations in 3D structure of the fibrin network observed, and why this phenomenon is more pronounced at low compared to intermediate or high ASA doses, deserve further investigations.

Effects of Three Months of Low Molecular Weight Heparin (dalteparin) Treatment After Bypass Surgery for Lower Limb Ischemia—A Randomised Placebo-controlled Double Blind Multicentre Trial

Objectives To test the hypothesis that long-term postoperative dalteparin (Fragmin ®, Pharmacia Corp) treatment improves primary patency of peripheral arterial bypass grafts (PABG) in lower limb ischemia patients on acetylsalicylic acid (ASA) treatment. Design Prospective randomised double blind multicenter study. Materials and methods Using a computer algorithm 284 patients with lower limb ischemia, most with pre-operative ischemic ulceration or partial gangrene, from 12 hospitals were randomised, after PABG, to 5000 IU dalteparin or placebo injections once daily for 3 months. All patients received 75 mg of ASA daily for 12 months. Graft patency was assessed at 1, 3 and 12 months. Results At 1 year, 42 patients had died or were lost to follow-up. Compliance with the injection schedule was 80%. Primary patency rate, in the dalteparin versus the control group, respectively, was 83 versus 80% (n.s.) at 3 months and 59% for both groups at 12 months. Major complication rates and cardiovascular morbidity were not different between the two groups. Conclusions In patients on ASA treatment, long-term postoperative dalteparin treatment did not improve patency after peripheral artery bypass grafting. Therefore, low molecular weight heparin treatment cannot be recommended for routine use after bypass surgery for critical lower limb ischemia.

Camptothecin accumulation in Camptotheca acuminata seedlings in response to acetylsalicylic acid treatment

Camptothecin is an anti-cancer alkaloid. Acetylsalicylic acid (ASA) treatment was evaluated as a potential tool for increasing camptothecin accumulation (concentration and yield) in Camptotheca acuminata. Increasing ASA concentration increased leaf camptothecin concentration, but stunted growth and decreased total leaf camptothecin yield. Thus, ASA treatment does not enhance camptothecin yield. Key words: Hydroponic culture, plant secondary metabolite

Kawasaki disease mimicking an acute appendicitis*1

Kawasaki disease mimicking an acute appendicitis*1

Effects of acetylsalicylic acid treatment on thyroid hormones, prolactins, and the stress response of tilapia (Oreochromis mossambicus).

The cyclooxygenase (COX) pathway converts arachidonic acid (ArA) into prostaglandins (PGs), which interact with the stress response in mammals and possibly in fish as well. Acetylsalicylic acid (ASA) is a COX inhibitor and was used to characterize the effects of PGs on the release of several hormones and the stress response of tilapia (Oreochromis mossambicus). Plasma PGE2 was significantly reduced at 100 mg ASA/kg body wt, and both basal PGE2 and cortisol levels correlated negatively with plasma salicylate. Basal plasma 3,5,3'-triiodothyronine (T3) was reduced by ASA treatment, whereas prolactin (PRL)188 increased at 100 mg ASA/kg body wt. ASA depressed the cortisol response to the mild stress of 5 min of net confinement. As expected, glucose and lactate were elevated in the stressed control fish, but the responses were blunted by ASA treatment. Gill Na+-K+-ATPase activity was not affected by ASA. Plasma osmolarity increased after confinement in all treatments, whereas sodium only increased at the high ASA dose. This is the first time ASA has been administered to fish in vivo, and the altered hormone release and the inhibition of the acute stress response indicated the involvement of PGs in these processes.

Inhibition of cytosolic phospholipase A 2 mRNA expression: a novel mechanism for acetylsalicylic acid-mediated growth inhibition and apoptosis in colon cancer cells

Acetylsalicylic acid (ASA) has been confirmed to inhibit proliferation and to induce apoptosis in human colorectal cancer cells in vitro. However, the mechanism by which ASA exhibits antiproliferative and proapoptotic effects in cyclooxygenase 2 (COX-2)-negative cells remains to be further elucidated. In the present study, SW480, a COX-2-negative colon cancer cell line, was treated with various concentrations of ASA (0, 2.5, 5, and 10 mM). The antiproliferative and proapoptotic effects of ASA were confirmed by MTT assay, flow cytometry of propidium iodide (PI)-stained cells, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay. After treatment with ASA, intracellular cyclic AMP (cAMP) levels were increased and the production of prostaglandin E 2 (PGE 2) was decreased. RT-PCR analysis revealed that treatment of ASA induced a concentration-dependent downregulation of cytosolic phospholipase A 2 (cPLA 2) mRNA expression in SW480 cells and also in two other colorectal cancer cell lines, Colo320 and HT-29 cells. Intracellular calcium levels were unaffected by ASA treatment. Our results indicate that the ASA-induced downregulation of cytosolic phospholipase A 2 mRNA expression might be a novel mechanism for ASA-mediated growth inhibition and apoptosis in colon cancer cells.