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Acetylsalicylic Acid (acetylsalicylic + acid)
Selected AbstractsThrombophilic Factors Do Not Predict Outcomes in Renal Transplant Recipients Under Prophylactic Acetylsalicylic AcidAMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2010L. Ghisdal A cohort of recipients of renal transplant after 2000 (N = 310) was prospectively screened on the day of transplantation and 1 month later for a panel of 11 thrombophilic factors to assess their effect on posttransplant outcomes. All patients received prophylactic acetylsalicylic acid, started before transplantation. The rate of thromboembolic events or acute rejection episodes during the first posttransplant year (primary composite endpoint) was 16.7% among patients free of thrombophilic factor (N = 60) and 17.2% in those with ,1 thrombophilic factor (N = 250) (p > 0.99). The incidence of the primary endpoint was similar among patients free of thrombophilic factors and those with ,2 (N = 135), or ,3 (N = 53) factors (16.3% and 15.1% respectively; p = 1) and in patients who remained thrombophilic at 1 month (15.7%; p = 0.84). None of the individual thrombophilic factor present at the day of transplantation was associated with the primary endpoint. The incidence of cardiovascular events at 1-year, serum creatinine at 1-year, 4-year actuarial graft and patient survival were not influenced by the presence of ,1 thrombophilic factor at baseline (p = NS). In conclusion, the presence of thrombophilic factors does not influence thromboembolic events, acute rejection, graft or patient survival in patients transplanted after 2000 and receiving prophylactic acetylsalicylic acid. [source] Activation of p53 signalling in acetylsalicylic acid-induced apoptosis in OC2 human oral cancer cellsEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 10 2003C.-C. Ho Abstract Background, Nonsteroidal anti-inflammatory drugs (NSAIDs) such as acetylsalicylic acid (ASA, aspirin) are well known chemotherapeutic agents of cancers; however, the signalling molecules involved remain unclear. The aim of this study was to investigate the possible existence of a putative p53-dependent pathway underlying the ASA-induced apoptosis in OC2 cells, a human oral cancer cell line. Materials and methods, The methyl tetrazolium (MTT) assay was employed to quantify differences in cell viability. DNA ladder formation on agarose electrophoresis was used as apoptosis assay. The expression levels of several master regulatory molecules controlling various signal pathways were monitored using the immunoblotting techniques. Flow cytometry was used to confirm the effect of ASA on cell cycle. Patterns of changes in expression were scanned and analyzed using the NIH image 1·56 software (NIH, Bethesda, MD, USA). All the data were analyzed by anova. Results, Acetylsalicylic acid reduced cell viability and presence of internucleosomal DNA fragmentation. In the meanwhile, phosphorylation of p53 at serine 15, accumulation of p53 and increased the expression of its downstream target genes, p21 and Bax induced by ASA. The expression of cyclooxygenase-2 was suppressed. Disruption of p53-murine double minute-2 (MDM2) complex formation resulted in increasing the expression of MDM2 60-kDa cleavage fragment. Inhibited the activation of p42/p44 mitogen-activated protein kinase (MAPK) by PD98059, a specific inhibitor of extracellular regulatory kinase (ERK), significantly decreased cell viability and enhanced the expression of p53 induced by ASA. The result of the cell-cycle analysis showed that ASA and PD98059 induced the cell cycle arrested at the G0/G1 phase and resulted in apoptosis. Conclusion, Nonsteroidal anti-inflammatory drug-inhibited cyclooxygenase is not the only or even the most important mechanism of inhibition. Our study presents evidences that activation of p53 signalling involved in apoptosis induced by ASA. Furthermore, the apoptotic effect was enhanced by blocking the activation of p42/p44 MAPK in response to treatment with ASA, thus indicating a negative role for p42/p44 MAPK. [source] Variable expression of CYP and Pgp genes in the human small intestineEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 6 2003M. Lindell Abstract Background ,The small intestine is receiving increased attention for its importance in drug metabolism. However, knowledge of the intervariability and regulation of the enzymes involved, cytochrome P450 and P-Glycoproteins (CYP and Pgp), is poor when compared with the corresponding hepatic enzymes. Methods ,The expression of eight different CYP genes and the Pgp were determined by reverse transcription polymerase chain reaction (RT-PCR) in 51 human duodenum biopsies. And the variability and correlation of expression was analyzed. Results ,Extensive interindividual variability was found in the expression of most of the genes. Only CYP2C9, CYP3A4 and Pgp were found in all samples. CYP1A2, CYP2A6 and CYP2E1 exhibited the highest interindividual variability. No strong correlation of expression existed between the genes. But a highly significant correlation was found between CYP2D6/1A2, 2D6/2E1, 1A2/2E1 and 2B6/2C9. Acetylsalicylic acid and omeprazole significantly increased the expression of CYPs 2A6, 2E1 and 3A4, respectively. Conclusions ,Extensive interindividual variability is characteristic for the expression of drug-metabolizing CYP and Pgp genes in human duodenum, and external factors such as drugs may further increase the variability. It is possible that the large interindividual variability may lead to variable bioavailability of orally used drugs and hence complicate optimal drug therapy, especially for drugs with a small therapeutic window. Elucidation of factors contributing to clinically important variances warrants further investigation. [source] The effects of acetylsalicylic acid on proliferation, apoptosis, and invasion of cyclooxygenase-2 negative colon cancer cellsEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 11 2002H.-G. Yu Summary Background Acetylsalicylic acid (ASA, aspirin), the most common nonsteroidal anti-inflammatory drug (NSAID), has been shown to have a protective effect against the incidence and mortality of colorectal cancer. However, the mechanism of its anticancer function remains unclear. The aim of this study was to determine the effects of acetylsalicylic acid on proliferation, apoptosis, and invasion in human cyclooxygenase-2 (COX-2) negative colorectal cancer cell lines. Materials and Methods After treatment with various concentrations of ASA, cell proliferation was measured in the human colon cancer cell line SW480. Apoptotic cells were identified by transmission electron microscopy, acridine orange staining, and flow cytometry. The invasive potential of SW480 cells was detected using an in vitro invasion assay. The production of carcinoembryonic antigen was measured by microparticle enzyme immunoassay. Expression of Bcl2, Bax, CD44v6, and nm23 were evaluated by immunocytochemistry. Results ASA significantly inhibited the proliferation of SW480 cells and stimulated apoptosis. Production of carcinoembryonic antigen and the invasive potential of SW480 cells were also inhibited by ASA. After treatment with ASA, down-regulation of Bcl2 and CD44v6 expression and up-regulation of nm23 expression were observed in SW480 cells. No obvious effect of ASA was found on Bax expression. Conclusion Our findings reveal that ASA inhibits the proliferation and promotes apoptosis in the human colon cancer cell line SW480. Down-regulation of Bcl2 expression might represent a potential mechanism by which ASA induces apoptosis in this COX-2 negative colon cancer cell line. Our results also suggest that ASA decreases the invasive potential of these colon cancer cells. Decreased CEA content and CD44v6 expression and elevated nm23 expression may contribute to the effect of ASA on invasive potential of SW480 colon cancer cells. [source] SPONTANEOUS COLONIC HEMATOMA: ENDOSCOPIC APPEARANCEDIGESTIVE ENDOSCOPY, Issue 2 2007Marcus Martins Dos Santos Intramural colonic hematoma is a rare complication of anticoagulation therapy. We report a patient under therapy with acetylsalicylic acid, low-molecular-weight heparin and clopidogrel for unstable angina, who presented with massive lower gastrointestinal bleeding secondary to spontaneous intramural colonic hematoma, with unremarkable coagulation tests. Diagnosis was promptly made by colonoscopy, and the patient was successfully managed with a conservative approach, with complete resolution of symptoms after 7 days. This is the first report of spontaneous intramural colonic hematoma presumed to be related to acetylsalicylic acid, enoxaparin and clopidogrel. [source] Coupling of solid-phase microextraction continuous bed (monolithic) capillaries with capillary zone electrophoresis for direct analysis of drugs in biological fluids,ELECTROPHORESIS, Issue 8 2008Reda Jarmalavi Abstract Hyperlink robust biocompatible solid-phase microextraction (SPME) devices were prepared using continuous bed (monolithic) restricted-access media (RAM) as the SPME capillary insert. The RAM-based SPME approach was able to simultaneously separate proteins from a biological sample, while directly extracting the active components of caffeine, paracetamol and acetylsalicylic acid from the drug NeoCitramonum. The devices were interfaced with a CZE system and fully automated analysis for sample preconcentration, desorption, separation and quantification of analytes was evaluated. Comparative study of in-line coupled SPME,CZE using RAM and RP capillary inserts was carried out. Using an SPME (RAM) insert, the calculated caffeine, paracetamol and acetylsalicylic acid LODs in a bovine plasma sample were 0.3, 0.8 and 1.9,ng/mL, respectively. [source] Activation of p53 signalling in acetylsalicylic acid-induced apoptosis in OC2 human oral cancer cellsEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 10 2003C.-C. Ho Abstract Background, Nonsteroidal anti-inflammatory drugs (NSAIDs) such as acetylsalicylic acid (ASA, aspirin) are well known chemotherapeutic agents of cancers; however, the signalling molecules involved remain unclear. The aim of this study was to investigate the possible existence of a putative p53-dependent pathway underlying the ASA-induced apoptosis in OC2 cells, a human oral cancer cell line. Materials and methods, The methyl tetrazolium (MTT) assay was employed to quantify differences in cell viability. DNA ladder formation on agarose electrophoresis was used as apoptosis assay. The expression levels of several master regulatory molecules controlling various signal pathways were monitored using the immunoblotting techniques. Flow cytometry was used to confirm the effect of ASA on cell cycle. Patterns of changes in expression were scanned and analyzed using the NIH image 1·56 software (NIH, Bethesda, MD, USA). All the data were analyzed by anova. Results, Acetylsalicylic acid reduced cell viability and presence of internucleosomal DNA fragmentation. In the meanwhile, phosphorylation of p53 at serine 15, accumulation of p53 and increased the expression of its downstream target genes, p21 and Bax induced by ASA. The expression of cyclooxygenase-2 was suppressed. Disruption of p53-murine double minute-2 (MDM2) complex formation resulted in increasing the expression of MDM2 60-kDa cleavage fragment. Inhibited the activation of p42/p44 mitogen-activated protein kinase (MAPK) by PD98059, a specific inhibitor of extracellular regulatory kinase (ERK), significantly decreased cell viability and enhanced the expression of p53 induced by ASA. The result of the cell-cycle analysis showed that ASA and PD98059 induced the cell cycle arrested at the G0/G1 phase and resulted in apoptosis. Conclusion, Nonsteroidal anti-inflammatory drug-inhibited cyclooxygenase is not the only or even the most important mechanism of inhibition. Our study presents evidences that activation of p53 signalling involved in apoptosis induced by ASA. Furthermore, the apoptotic effect was enhanced by blocking the activation of p42/p44 MAPK in response to treatment with ASA, thus indicating a negative role for p42/p44 MAPK. [source] COX-2-independent antiproliferative action of acetylsalicylic acid in human colon cancer cellsEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 11 2002M. N. Göke No abstract is available for this article. [source] The effects of acetylsalicylic acid on proliferation, apoptosis, and invasion of cyclooxygenase-2 negative colon cancer cellsEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 11 2002H.-G. Yu Summary Background Acetylsalicylic acid (ASA, aspirin), the most common nonsteroidal anti-inflammatory drug (NSAID), has been shown to have a protective effect against the incidence and mortality of colorectal cancer. However, the mechanism of its anticancer function remains unclear. The aim of this study was to determine the effects of acetylsalicylic acid on proliferation, apoptosis, and invasion in human cyclooxygenase-2 (COX-2) negative colorectal cancer cell lines. Materials and Methods After treatment with various concentrations of ASA, cell proliferation was measured in the human colon cancer cell line SW480. Apoptotic cells were identified by transmission electron microscopy, acridine orange staining, and flow cytometry. The invasive potential of SW480 cells was detected using an in vitro invasion assay. The production of carcinoembryonic antigen was measured by microparticle enzyme immunoassay. Expression of Bcl2, Bax, CD44v6, and nm23 were evaluated by immunocytochemistry. Results ASA significantly inhibited the proliferation of SW480 cells and stimulated apoptosis. Production of carcinoembryonic antigen and the invasive potential of SW480 cells were also inhibited by ASA. After treatment with ASA, down-regulation of Bcl2 and CD44v6 expression and up-regulation of nm23 expression were observed in SW480 cells. No obvious effect of ASA was found on Bax expression. Conclusion Our findings reveal that ASA inhibits the proliferation and promotes apoptosis in the human colon cancer cell line SW480. Down-regulation of Bcl2 expression might represent a potential mechanism by which ASA induces apoptosis in this COX-2 negative colon cancer cell line. Our results also suggest that ASA decreases the invasive potential of these colon cancer cells. Decreased CEA content and CD44v6 expression and elevated nm23 expression may contribute to the effect of ASA on invasive potential of SW480 colon cancer cells. [source] The effect of topically applied salicylic compounds on serotonin-induced scratching behaviour in hairless ratsEXPERIMENTAL DERMATOLOGY, Issue 4 2002J. S. Thomsen Abstract: There is a strong need for antipruritic substances for treating itch in clinical dermatology. In one recent human study, topically applied acetylsalicylic acid has been described to rapidly decrease histamine-induced itch. We have established a model for periferally elicited pruritus by injecting serotonin into the rostral back area (neck) in rats. Using this model, we aimed to investigate the antipruritic potential of four different salicylic compounds, which all possess different skin penetration characteristics. Eighteen rats were studied for 6 weeks. Prior to serotonin injections (2 mg/ml, 50 µl), 10 µl of test substances was applied to a circular area 18 mm in diameter. The four substances were salicylic acid, butyl salicylate, diethylamine salicylate and salicylamide, all solubilized in dimethyl isosorbide to a concentration of 5% w/w. Diethylamine salicylate and salicylamide were previously shown to be slowly absorbed through rat skin in contrast to salicylic acid and butyl salicylate. After serotonin injections, scratching was monitored by video recording for 1.5 h. Compared with the vehicle, a lower number of scratch sequences were seen when diethylamine salicylate (P < 0.001) and salicylamide (P = 0.005) had been applied. The numbers of scratch sequences were lower with diethylamine salicylate and salicylamide than with the vehicle throughout the 1.5-h study period. We conclude that topical application of diethylamine salicylate and salicylamide could suppress serotonin-induced scratching in rats. The antipruritic effect seems to be related to the slow drug release of the two substances. The results may be clinically relevant as serotonin induces itch in humans. [source] The release of elongated, sheathed ascospores from bottle-shaped asci in Dipodascus geniculatusFEMS YEAST RESEARCH, Issue 2 2007Ané Van Heerden Abstract Yeasts use different mechanisms to release ascospores of different lengths from bottle-shaped asci. Round to oval-shaped ascospores are enveloped in oxylipin-coated compressible sheaths, enabling ascospores to slide past each other when they reach the narrowing ascus neck. However, more elongated ascospores do not contain sheaths, but are linked by means of oxylipin-coated interlocked hooked ridges on the surfaces of neighboring ascospores, thereby keeping them aligned while they are pushed towards the ascus tip by turgor pressure. In this study, we found elongated, oxylipin-coated sheathed ascospores in Dipodascus geniculatus that are released effectively from bottle-shaped asci without alignment. This is possible because the ascus neck and opening have a diameter that is the same as the length of the ascospore, thus allowing the ascospores to turn sideways without blocking the ascus when they are released. We found that increased concentrations of acetylsalicylic acid inhibit both ascospore release and 3-hydroxy oxylipin production in this yeast, thereby implicating this oxylipin in sexual reproduction. [source] Oxidative stress parameters after combined fluoxetine and acetylsalicylic acid therapy in depressive patientsHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 4 2009Piotr Ga, ecki Abstract Objective There are numerous reports indicating disturbed equilibrium between oxidative processes and antioxidative defense in patients with depression. Moreover, depressive patients are characterized by the presence of elements of an inflammatory process, which is one of the sources of reactive oxygen species (ROS). In view of the above, it was decided to study both the effect of fluoxetine monotherapy and that of fluoxetine co-administered with acetylsalicylic acid on lipid peroxidation and antioxidative defense in patients with the first depressive episode in their life. Method Seventy seven patients with major depressive disorder (MDD), divided into two groups were included in the study. The first group, consisting of 52 patients, received fluoxetine 20 mg, and the second one, in addition to fluoxetine 20 mg, received 150 mg of acetylsalicylic acid. The activity of antioxidative enzymes, copper-zinc superoxide dismutase (CuZnSOD, SOD1), catalase (CAT), glutathione peroxidase (GPSH-x) and the concentration of malonyldialdehyde (MDA) was determined in erythrocytes, whereas the total antioxidant status (TAS) was determined in the plasma. All parameters were measured before and after three month therapy. Results The obtained results indicate a significant decrease in the activity of SOD1, CAT and GSHP-x, as well as in MDA concentration after the combined therapy. Also a significant TAS increase was observed after the combined therapy. The study demonstrated that combined therapy with fluoxetine and ASA is characterized by the same efficacy and clinical safety as fluoxetine monotherapy, resulting additionally in improvement of oxidative stress parameters in the patients treated for depression. Copyright © 2009 John Wiley & Sons, Ltd. [source] Juvenile psoriatic arthritis with nail psoriasis in the absence of cutaneous lesionsINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 1 2000Carola Duran-McKinster MD A 4-year-old white boy without a significant family history had morning stiffness and painful swelling of his left knee and ankle, right elbow, and dorsolumbar region of 2 months' evolution. The following laboratory studies were within normal limits: complete blood cell count, C-reactive protein (CRP), latex, antistreptolysin, and antinuclear antibodies. Rheumatoid factor was negative and an increase in the erythrocyte sedimentation rate (ESR) was detected (56 mm/h). The pediatric department made an initial diagnosis of juvenile rheumatoid arthritis, and treatment with acetylsalicylic acid at 100 mg/kg/day and naproxen at 10 mg/kg/day was started. A thick, yellowish toenail was diagnosed as onychomycosis. No mycologic investigations were performed. Intermittent episodes of painful arthritis of different joints were present. The radiographic features of the peripheral joints included: narrow joint spaces, articular erosions, soft tissue swelling, and diffuse bony demineralization. Characteristic bilateral sacroiliitis and a swollen tendon sheath on the left ankle were detected. At 11 years of age the nail changes had extended to five other toenails and to four fingernails, were yellow,brown in color, and showed marked subungual hyperkeratosis ( Figs 1, 2). The rest of the nails showed significant nail pitting. Trials of griseofulvin alternated with itraconazole in an irregular form for five consecutive years resulted in no clinical improvement, which prompted a consultation to our dermatology department. On three different occasions, KOH nail specimens were negative for fungus, but the presence of parakeratotic cells aroused the suspicion of psoriasis. A complete physical examination was negative for psoriatic skin lesions. A nail bed biopsy specimen was characteristic of nail psoriasis ( Fig. 3). Figure 1. Thickened nails with severe subungual hyperkeratosis in five fingernails Figure 2. Secondary deformity of nail plate. No "sausage" fingers were observed Figure 3. Light microscopic appearance of a nail biopsy specimen showing parakeratotic hyperkeratosis, elongation of interpapillary processes, and Munroe abscess (arrow) (hematoxylin and eosin stain, ×40) The following human leukocyte antigens (HLAs) were positive: A9, A10, B12, B27, Cw1, Bw4, DR6, DR7, DQ1, DQ2, and DR53. A diagnosis of juvenile psoriatic arthritis associated with nail psoriasis was made. Toenail involvement became so painful that walking became very difficult. Occlusive 40% urea in vaseline applied to the affected toenails for 48 h resulted in significant improvement. Currently, the patient is 20 years old with nail involvement, but no psoriatic skin lesions have ever been observed. [source] What do we know about the genetics of aspirin intolerance?JOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 5 2008N. S. Palikhe MPharm Summary Although acetylsalicylic acid is prescribed for a broad range of diseases, it can induce a wide array of clinically recognized hypersensitivity reactions, including aspirin-intolerant asthma (AIA) with rhinitis and aspirin-intolerant urticaria (AIU) with anaphylaxis. Altered eicosanoid metabolism is the generally accepted mechanism of aspirin intolerance; the overproduction of cysteinyl leucotrienes has been suggested to play a causative role in both AIA and AIU. Genetic markers suggested for AIA include HLA-DPBI*0301, leucotriene C4 synthase (LTC4S), ALOX5, CYSLT, PGE2, TBXA2R and TBX21. Similarly, HLA-DB1*0609, ALOX5, FCER1A and HNMT have been identified as possible genetic markers for AIU. An additional low-risk genetic marker for AIA is MS4A2, which encodes the beta-chain of FCER1. Other single and sets of two or more interacting genetic markers are currently being investigated. Analyses of the genetic backgrounds of patients with AIA and AIU will promote the development of early diagnostic and therapeutic interventions, which may reduce the incidence of AIA and AIU. [source] Inhibition of Oxidative and Antioxidative Enzymes by Trans-ResveratrolJOURNAL OF FOOD SCIENCE, Issue 2 2001X. Fan ABSTRACT: Trans-resveratrol, a phytoalexin produced by a variety of plants, has been shown to inhibit oxidative enzymes in an animal cell system. Its effect on several oxidative and antioxidative enzymes from plants was investigated using in vitro assays. Trans-resveratrol inhibited superoxide dismutase, lipoxygenase, catalase, peroxidase, polyphenol oxidase, and 1-aminocyclopropane-1-carboxylic acid oxidase with apparent KI's of 10, 90, 100, 255, 305, and 350 ,M, respectively. Trans-resveratrol inhibited lipoxygenase activity more effectively than other lipoxygenase inhibitors, including propyl gallate, ibuprofen, ursolic acid, acetylsalicylic acid, and salicylhydroxamic acid. [source] Fracture risk associated with the use of morphine and opiatesJOURNAL OF INTERNAL MEDICINE, Issue 1 2006P. VESTERGAARD Abstract. Objectives., To study the effect of morphine and opiates on fracture risk. Design., Case,control study. Setting., Nationwide register-based study. Subjects., Cases were all subjects with any fracture sustained during the year 2000 (n = 124 655). For each case, three controls (n = 373 962) matched on age and gender were randomly drawn from the background population. The primary exposure variables were use of morphine and opiates. Morphine and other opiates had been used by 10 015 (8.0%) of the case subjects and 12 108 (3.2%) of the controls. Adjustments were made for several confounders including prior fracture, and use of weak analgesics [nonsteroidal anti-inflammatory drugs, acetylsalicylic acid (ASA) and acetaminophene]. The effect of dose was examined by stratifying for cumulated dose (defined daily dose). Main outcome measure., Fracture. Results., Morphine (1.47, 95% CI 1.37,1.58), fentanyl (2.23, 95% CI 1.89,2.64), methadone (1.39, 95% CI 1.05,1.83), oxycodone (1.36, 95% CI 1.08,1.69), nicomorphine (1.57, 95% CI 1.38,1.78), ketobemidone (1.07, 95% CI 1.02,1.13), tramadol (1.54, 95% CI 1.49,1.58) and codeine (1.16, 95% CI 1.12,1.20) were all associated with an increase in overall fracture risk. No increase was present for buprenorphine (0.86, 95% CI 0.79,0.95), pethidine (0.98, 95% CI 0.89,1.08), dextropropoxiphene (1.02, 95% CI 0.90,1.16), and combinations of ASA and codeine (0.94, 95% CI 0.88,1.01). Conclusions., An increased fracture risk is seen in users of morphine and opiates. The reason for this may be related to the risk of falls due to central nervous system effects such as dizziness. [source] Synergistic inhibitory effect of ascorbic acid and acetylsalicylic acid on prostaglandin E2 release in primary rat microgliaJOURNAL OF NEUROCHEMISTRY, Issue 1 2003Bernd L. Fiebich Abstract Ascorbic acid (vitamin C) has been suggested to protect cerebral tissue in a variety of pathophysiological situations such as head trauma, ischemia or Alzheimer's disease. Most of these protective actions have been attributed to the antioxidative capacity of ascorbic acid. Besides the presence of elevated levels of oxygen radicals, prostaglandins produced by neurones and microglial cells seem to play an important role in prolonged tissue damage. We investigated whether ascorbic acid alone inhibits prostaglandin E2 (PGE2) synthesis and may augment the inhibitory effect of acetylsalicylic acid on prostaglandin synthesis. Ascorbic acid dose-dependently inhibited PGE2 synthesis in lipopolysaccharide-treated primary rat microglial cells (IC50 = 3.70 µm). In combination with acetylsalicylic acid (IC50 = 1.85 µm), ascorbic acid augmented the inhibitory effect of acetylsalicylic acid on PGE2 synthesis (IC50 = 0.25 µm in combination with 100 µm ascorbic acid). Ascorbic acid alone or in combination with acetylsalicylic acid did not inhibit cyclooxygenase-2 (COX-2) protein synthesis but inhibited COX-2 enzyme activity. Our results show that ascorbic acid and acetylsalicylic acid act synergistically in inhibiting PGE2 synthesis, which may help to explain a possible protective effect of ascorbic acid in various brain diseases. [source] NSAIDs protect dopaminergic neurons against 6-OHDA and MPP+ toxicityJOURNAL OF NEUROCHEMISTRY, Issue 2002P. Werner Endogenous and environmental neurotoxins are among the suspected causes of the loss of dopaminergic (DA) neurons in Parkinson's disease (PD). Non-steroidal anti-inflammatory drugs (NSAIDs) reduce inflammation by inhibiting cyclooxygenase (COX)-dependent synthesis of prostaglandins (PG) from arachidonic acid. NSAIDs decrease the incidence of Alzheimer's disease, but little is known about their potential benefit for PD. Therefore, we examined whether NSAIDs could protect DA neurons from neurotoxic insults. NSAIDs can protect DA neurons against excitotoxicity (Casper et al. 2000), and against 6-hydroxydopamine (6-OHDA) toxicity (Carrasco et al. 2001). Here, we compared in primary mesencephalic/DA neuron cultures the effect of NSAIDs on the toxicity of 1-methyl-phenylpyridinium (MPP+) or 6-OHDA. 6-OHDA significantly (*p < 0.0001) increased PG production, whereas MPP+ did not (p < 0.05). We then compared the competitive/unspecific COX inhibitors ibuprofen and naproxen and the noncompetitive/unspecific inhibitor acetylsalicylic acid (ASA, aspirin) for their ability to protect DA neurons against either 6-OHDA or MPP+ toxicity. Interestingly, all three nonselective COX inhibitors protected DA neurons in cultures against both 6-OHDA and MPP+ (p < 0.05), despite the difference in PG induction by 6-OHDA vs. MPP+. The selective COX-2 inhibitor NS398 did protect DA neurons against 5 ,m MPP+ (*p < 0.05), but failed to protect DA neurons against 5 ,m 6-OHDA (p < 0.05). Our results suggest that COX-inhibitors may have neuroprotective benefits unrelated to inhibition of PG synthesis, and that 6-OHDA and MPP+ have partially overlapping mechanisms of neurodegeneration possibly involving COX activity. Acknowledgement:, Supported, in part, by the International Federation for Parkinson's disease, NY, NY. [source] An examination of binding motifs associated with inter-particle interactions between facetted nano-crystals of acetylsalicylic acid and ascorbic acid through the application of molecular grid-based search methods,JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 12 2009R.B. Hammond Abstract Grid-based intermolecular search methods using atom,atom force fields are used to assess the structural nature of potential crystal,crystal interfacial binding associated with the examination of representative pharmaceutical formulation components, viz acetylsalicylic acid (aspirin) and ascorbic acid (vitamin C). Molecular models of nano-sized molecular clusters for these two compounds, shaped in accordance with an attachment energy model of the respective particle morphologies, are constructed and used together with a grid-based search method to model the likely inter-particle interactions. The most-stable, mutual alignments of the respective nano-clusters based on their interaction energies are identified in the expectation that these are indicative of the most likely inter-particle binding configurations. The stable inter-particle binding configurations identified reveal that the number of interfacial hydrogen bonds formed between the binding particles is, potentially, an important factor in terms of the stability of inter-particle cohesion. All preferred inter-particle alignments are found to involve either the (1,0,0) or the (1,1,0) face of aspirin crystals interacting with a number of the growth forms of ascorbic acid. Four main types of interfacial hydrogen bonds are found to be associated with inter-particle binding and involve acceptor,donor interactions between hydroxyl, carbonyl, ester and lactone acceptor groups and hydroxyl donor groups. This hydrogen bonding network is found to be consistent with the surface chemistry of the interacting habit faces with, in general, the number of hydrogen bonds increasing for the more stable alignments. The likely usefulness of this approach for predicting solid-state formulation properties is reviewed. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:4589,4602, 2009 [source] Polymorphism of NCX4016, an NO-releasing derivative of acetylsalicylic acidJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 3 2004A. Foppoli Abstract NCX4016 [2-acetoxybenzoic acid 3,-(nitrooxymethyl)phenyl ester] is a recently developed nitrooxy-derivative of aspirin with improved antiinflammatory, analgesic, and antithrombotic activity as well as increased gastrointestinal safety. Systematic polymorphic screening performed with different solvents and preparation methods resulted in the identification of two polymorphs, designated Forms I and II. They were characterized by scanning electron microscopy, powder X-ray diffraction, thermal analyses, and infrared spectroscopy; the crystal structure of polymorph I was solved by single-crystal X-ray analysis and compared with that of aspirin. Finally, intrinsic dissolution rate studies and calculations according to the melting data method were performed to assess the thermodynamic relationship between the two polymorphs. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:521,531, 2004 [source] Aspirin, 110 years laterJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 2009C. PATRONO Summary., Although conceived at the end of the 19th century as a synthetic analgesic agent with improved gastric tolerability vs. naturally occurring salicylates, acetylsalicylic acid (marketed as aspirin in 1899) turned out to be an ideal antiplatelet agent about 90 years later, following the understanding of its mechanism of action, the development of a mechanism-based biomarker for dose-finding studies, and the initiation of a series of appropriately sized, randomized clinical trials to test its efficacy and safety at low doses given once daily. At the turn of its 110th anniversary, aspirin continues to attract heated debates on a number of issues including (i) the optimal dose to maximize efficacy and minimize toxicity; (ii) the possibility that some patients may be ,resistant' to its antiplatelet effects; and (iii) the balance of benefits and risks in primary vs. secondary prevention. [source] Systematic review: the global incidence and prevalence of peptic ulcer diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 9 2009J. J. Y. SUNG Summary Background, Peptic ulcer disease (PUD) is most commonly associated with Helicobacter pylori infection and the use of acetylsalicylic acid (ASA) and nonsteroidal anti-inflammatory drugs (NSAIDs). The management of H. pylori infection has improved radically in recent years; however, the prescription of ASA and NSAIDs has increased over the same period. Aim, To evaluate the current global incidence and prevalence of PUD by systematic review of the literature published over the last decade. Methods, Systematic searches of PubMed, EMBASE and the Cochrane library. Results, The annual incidence rates of PUD were 0.10,0.19% for physician-diagnosed PUD and 0.03,0.17% when based on hospitalization data. The 1-year prevalence based on physician diagnosis was 0.12,1.50% and that based on hospitalization data was 0.10,0.19%. The majority of studies reported a decrease in the incidence or prevalence of PUD over time. Conclusions, Peptic ulcer disease remains a common condition, although reported incidence and prevalence are decreasing. This decrease may be due to a decrease in H. pylori -associated PUD. [source] Canadian consensus guidelines on long-term nonsteroidal anti-inflammatory drug therapy and the need for gastroprotection: benefits versus risksALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2009A. ROSTOM Summary Background, Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used, but are not without risks. Aim, To provide evidence-based management recommendations to help clinicians determine optimal long-term NSAID therapy and the need for gastroprotective strategies based on an assessment of both gastrointestinal (GI) and cardiovascular (CV) risks. Methods, A multidisciplinary group of 21 voting participants revised and voted on the statements and the strength of evidence (assessed according to GRADE) at a consensus meeting. Results, An algorithmic approach was developed to help manage patients who require long-term NSAID therapy. The use of low-dose acetylsalicylic acid in patients with high CV risk was assumed. For patients at low GI and CV risk, a traditional NSAID alone may be acceptable. For patients with low GI risk and high CV risk, full-dose naproxen may have a lower potential for CV risk than other NSAIDs. In patients with high GI and low CV risk, a COX-2 inhibitor plus a proton pump inhibitor (PPI) may offer the best GI safety profile. When both GI and CV risks are high and NSAID therapy is absolutely necessary, risk should be prioritized. If the primary concern is GI risk, a COX-2 inhibitor plus a PPI is recommended; if CV risk, naproxen 500 mg b.d. plus a PPI would be preferred. NSAIDs should be used at the lowest effective dose for the shortest possible duration. Conclusion, More large, long-term trials that examine clinical outcomes of complicated and symptomatic upper and lower GI ulcers are needed. [source] Angioedema from angiotensin-converting enzyme (ACE) inhibitor treated with complement 1 (C1) inhibitor concentrateACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 1 2006E. W. Nielsen Background:, Up to seven in every 1000 patients experience angioedema from angiotensin-converting enzyme (ACE) inhibitors, even after many years of use. In 2003, every 20th Norwegian used an ACE inhibitor. Case report:, A 61-year-old woman with chronic obstructive pulmonary disease and a past acute myocardial infarction had used 7.5 mg of ramipril daily for the past 7 years. She also used acetylsalicylic acid, simvastatin, theophylline and salmeterol. One night she woke up with edema of the tongue. On hospital arrival, 250 mg of hydrocortisone and 5 mg of dexchlorpheniramine were given intravenously (i.v.) and 0.3 mg of epinephrine was given subcutaneously (s.c.). The edema of the tongue progressed over the next 8 h and made the tongue protrude. Fiberscopy revealed glassy edema of the arytenoids. Inspiratory stridor was heard and the patient could not speak. She became increasingly uneasy and restless. Berinert® complement 1 (C1) inhibitor concentrate (1500 units) was administered i.v. Over the following 20 min, stridor gradually subsided, the patient calmed and she was able to talk. Discussion:, ACE inhibitor-provoked angioedema shares many clinical features with hereditary angioedema (HAE), including a limited effect of steroids, antihistamines and epinephrine. HAE, caused by excess bradykinin formation as a result of C1 inhibitor deficiency, usually has its laryngeal edema effectively reversed by C1 inhibitor in less than 0.5 h. Although patients experiencing ACE inhibitor-provoked angioedema have normal C1 inhibitor values, as in our patient, excess bradykinin is probably important as ACE breaks down bradykinin. It is unknown why ACE inhibitor-provoked angioedema appears in some and sometimes after many years of use. Conclusion:, We believe that C1 inhibitor was effective in reversing the ACE inhibitor-induced angioedema in our patient. [source] Postpacemaker Implant Pericarditis: Incidence and Outcomes with Active-Fixation LeadsPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 5 2002SOORI SIVAKUMARAN SIVAKUMARAN, S., et al.: Postpacemaker Implant Pericarditis: Incidence and Outcomes with Active Fixation Leads. Pericarditis has been noted as a potential complication of pacemaker implantation. This study evaluated the risk of developing pericarditis following pacemaker implantation with active-fixation atrial leads. Included were 1,021 consecutive patients (mean age 73.4 ± 0.4 years, range 16,101 years; 45.2% women) undergoing new pacemaker system implantation between 1991 and 1999 who were reviewed for the complication of pericarditis. The incidence and outcomes of postimplantation pericarditis in patients receiving active-fixation atrial leads were compared to those not receiving these leads. Of 79 patients who received active-fixation atrial leads, 4 (5%) developed pericarditis postpacemaker implantation. Of 942 patients with passive-fixation atrial leads or no atrial lead (i.e., a ventricular lead only), none developed pericarditis postoperatively (P < 0.001). Of patients receiving active-fixation ventricular leads only (n = 97), none developed pericarditis. No complications were apparent at the time of implantation in patients who developed pericarditis. Pleuritic chest pain developed between 1 and 28 hours postoperatively. Three patients had pericardial rubs without clinical or echocardiographic evidence of tamponade. They were treated conservatively with acetylsalicylic acid or ibuprofen and their symptoms resolved without sequelae in 1,8 days. One patient (without pericardial rub) died due to cardiac tamponade on postoperative day 6. Postmortem examination revealed hemorrhagic pericarditis with no gross evidence of lead perforation. Pericarditis complicates pacemaker implantation in significantly more patients who receive active-fixation atrial leads. It may be precipitated by perforation of the atrial lead screw through the thin atrial wall. Patients developing postoperative pericarditis should be followed closely due to the risk of cardiac tamponade. [source] Essential versus reactive thrombocythemia in children: Retrospective analyses of 12 casesPEDIATRIC BLOOD & CANCER, Issue 1 2007Abeer Abd El-Moneim Abstract Background Essential thrombocythemia (ET) rarely occurs in the pediatric population and little is known about the clinical course and the molecular characteristics. Procedure In this retrospective multi-institutional study we examine the clinical, hematological, and molecular features of 12 children aged 5,16 years with thrombocytosis and a suspected diagnosis of ET. Results Median follow-up was 59 months (range 10,72). Seven patients presented with clinical symptoms potentially related to thrombocytosis. The remaining five patients were diagnosed incidentally. Median platelet count at diagnosis was 1,325,×,109/L (range 600,3,050). In 11 out of 12 cases bone marrow morphology was consistent with ET, the remaining patient had chronic idiopathic myelofibrosis. Cytogenetic analyses were normal in all studied cases and only one out of nine analyzed cases harbored a JAKV617F allele. Within 6 months after initial presentation one patient who was initially asymptomatic developed thrombosis and another patient had mild bleeding. Eight patients were treated with acetylsalicylic acid, one patient received hydroxyurea, and two patients received anagrelide. At last follow-up, all patients were alive and none had developed leukemia. Five patients experienced hematological remission. Two children had not received any therapy. During the course of their disease, nine patients developed symptoms possibly attributable to an elevated platelet count. Conclusions In JAK2 mutation negative cases, long-term follow-up is helpful to distinguish between primary and secondary thrombocytosis. Secondary cases are not associated with organomegaly but may present with unspecific symptoms. Indications for treatment in children remain unclear. Pediatr Blood Cancer 2007;49:52,55. © 2006 Wiley-Liss, Inc. [source] Allergic Reactions Due to Ibuprofen in ChildrenPEDIATRIC DERMATOLOGY, Issue 1 2001M. Díaz Jara M.D. We present two instances of adverse reaction to pediatric ibuprofen, an acute urticaria and a fixed drug eruption, with tolerance to acetylsalicylic acid (ASA) and acetaminophen, in what seems to be hypersensitivity to the propionic acid group. Although these reactions are very rare and ibuprofen is still very safe, we think it is important to know about the possible side effects in order to recognize and treat them when they occur. [source] Sex Differences in Outcomes of Sinus Surgery,THE LARYNGOSCOPE, Issue 7 2006Sabrina Mendolia-Loffredo MS Abstract Purpose: Sex has been demonstrated to affect outcome in many diseases. Our current aim is to investigate the relationship between sex and outcomes of endoscopic sinus surgery (ESS) in patients with chronic rhinosinusitis (CRS). Methods: Forty-four males and 73 females undergoing ESS for CRS with a mean follow-up of 1.4 years were evaluated prospectively. Computed tomography (CT), endoscopy, and quality of life (QOL) assessment was performed. Univariate analyses were performed to evaluate whether sex was predictive of outcome. Multiple logistic regression analysis was performed to evaluate sex association with patient factors predictive of outcome. Results: Although no sex differences in CT and endoscopy were observed (CT, P = .107 and endoscopy, P > .1), females consistently scored worse than males on disease-specific QOL pre- and postoperatively. Importantly, there was no effect of sex on improvement/change scores for the QOL instruments. Predictive Models and Multiple Logistic Regression Analysis: Sex was not found to be predictive of QOL or endoscopic outcome. Female sex was, however, associated with acetylsalicylic acid (ASA) intolerance and depression, both factors that have been associated with poorer outcome. Conclusion: Despite similarities in objective disease measures, females report significantly worse QOL scores pre- and postoperatively. Postoperative improvement did not differ by sex, nor was sex predictive of postoperative outcome. Sex differences in QOL reflect sex differences in ASA intolerance and depression, both more prevalent in females. [source] Thrombophilic Factors Do Not Predict Outcomes in Renal Transplant Recipients Under Prophylactic Acetylsalicylic AcidAMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2010L. Ghisdal A cohort of recipients of renal transplant after 2000 (N = 310) was prospectively screened on the day of transplantation and 1 month later for a panel of 11 thrombophilic factors to assess their effect on posttransplant outcomes. All patients received prophylactic acetylsalicylic acid, started before transplantation. The rate of thromboembolic events or acute rejection episodes during the first posttransplant year (primary composite endpoint) was 16.7% among patients free of thrombophilic factor (N = 60) and 17.2% in those with ,1 thrombophilic factor (N = 250) (p > 0.99). The incidence of the primary endpoint was similar among patients free of thrombophilic factors and those with ,2 (N = 135), or ,3 (N = 53) factors (16.3% and 15.1% respectively; p = 1) and in patients who remained thrombophilic at 1 month (15.7%; p = 0.84). None of the individual thrombophilic factor present at the day of transplantation was associated with the primary endpoint. The incidence of cardiovascular events at 1-year, serum creatinine at 1-year, 4-year actuarial graft and patient survival were not influenced by the presence of ,1 thrombophilic factor at baseline (p = NS). In conclusion, the presence of thrombophilic factors does not influence thromboembolic events, acute rejection, graft or patient survival in patients transplanted after 2000 and receiving prophylactic acetylsalicylic acid. [source] Sticky Platelet Syndrome: An Underrecognized Cause of Graft Dysfunction and Thromboembolic Complications in Renal Transplant RecipientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 7 2007A. S. Mühlfeld Sticky platelet syndrome (SPS) leads to hyperaggregabilty of platelets in response to physiologic stimuli. In this report we describe three patients with clinical symptoms of SPS after renal transplantation. The first patient developed an infarction of her transplant kidney with additional, subsequent renal microinfarctions. The second patient suffered multiple strokes and deep vein thrombosis with episodes of pulmonary embolism and ischemic bowel disease due to colonic microinfarctions. The third patient experienced a long episode of unexplained respiratory and graft dysfunction immediately after transplantation until therapy for SPS was initiated, at which point symptoms resolved quickly. Kidney transplant recipients with SPS may be at increased risk of developing thrombosis, given that most immunosuppressive drugs are known to induce either endothelial cell damage or augment platelet aggregation. All patients awaiting renal transplantation should be screened for a history of thrombosis and, if appropriate, tested for SPS. Affected patients should receive dose-adjusted acetylsalicylic acid. [source] | |||||||||||||||||||||||||||||||||||||