Analgesic Effects of Tetrodotoxin Combined with Acetylsalicylic Acid on Acetic Acid-induced Abdominal Constriction and Formalin Test in Mice

Aim To study the effects of tetrodotoxin （TTX） combined with acetylsalicylic acid （ASA） on nociceptive stimulus in mice. Methods To assess the antinociceptive effects of TTX, ASA or TTX plus ASA, the acetic acid-induced abdominal constriction test and formalin pain test were used. Results TTX （0.5 - 4.0 μg· kg^-1 ） or ASA （25 - 200 mg· kg^-1 ） im produced a significant inhibition of acetic acid-induced abdominal constriction. The median inhibitory doses （ID508） were 2.1 μg· kg^-1 for TTX（ and 64 mg· kg^-1 for ASA. TTX and ASA also showed a dose-dependent inhibition of the second phase response in the formalin pain model, the ID508, being 2.3μg·kg^-1 and 74.2 mg· kg^-1, respectively. The ihteraction between TTX and ASA was synergistic, as evidenced by the fact that （1） when ASA alone compared with the combination of TTX （0.79 μg · kg^-1 or 0.39μg· kg^-1 ） and ASA, the ID508, of ASA reduced from 64.0 mg· kg^-1 to 5.8 mg· kg^-1 or 12.6 mg· kg^-1, and from 74.2 mg· kg^-1 to 7.4 mg· kg^-1 or 13.0 mg· kg^-1 on tile two models of nociceptive tests, respectively; and that （2） synergism in the analgesic effects was shown by isobiolographic analysis. Conclusion TTX, ASA and the combination of the two drags produce analgesic effects in acetic acid-induced abdominal constriction test and formalin-induced pain test. The interactions between TTX and ASA may be useful in developing novel analgesic agents.

Effects of Acetylsalicylic Acid and Calcium Chloride on Photosynthetic Apparatus and Reactive Oxygen-Scavenging Enzymes in Chrysanthemum Under Low Temperature Stress with Low Light

The effects of acetylsalicylic acid （ASA）, CaCl2, and ASA ＋ CaCl2 on the photosynthetic apparatus and antioxidant enzyme activities were investigated in chrysanthemum Jinba （a cut flower cultivar） under low temperature stress with low light （TL stress） （16/12℃, day/night, PFD 100 μmol m^-2 s-1）. The results showed that under TL stress, the net photosynthesis rate （Pn）, carboxylation efficiency （CE）, apparent quantum yield （AQY）, maximal photochemical efficiency （Fv/Fm） of PSII, quantum yield of PSII electron transport （ФPSII）, and photochemical quenching （qP） of the chrysanthemum leaves in all treatments were significantly decreased, but the decreases were alleviated by ASA, CaCl2, and ASA ＋ CaCl2 treatments compared with the controls. The alleviating effect of ASA ＋ CaCI2 was better than either ASA or CaCl2 single treatment. Moreover, the ASA ＋ CaCl2 treatment highly improved the chlorophyll content, relatively improved the number and size of chloroplast and starch grain in the leaves of chrysanthemum plants compared with ASA and CaCl2 treatments. It was indicated that ASA and/or CaCI2 could regulate the photosynthetic functions in the leaves of chrysanthemum plants to enhance the resistance against TL stress. On the other hand, reduction in relative conductance rate implied that ASA and/ or CaCl2 could protect from membrane injury in leaves of chrysanthemum plants. The activities of SOD, POD, and CAT in the treated leaves of chrysanthemum were increased as compared with the controls. It was suggested that ASA and/or CaCl2 had positive regulation effects on the defence enzyme activities in chrysanthemum leaves which could protect the photosynthetic apparatus to a certain degree under the TL stress. In brief, the treatment of ASA together with CaCl2 was better for chrysanthemum plants to adapt TL stress than single ASA or CaCl2 treatments.

Acetylsalicylic acid supplementation improves protein utilization efficiency while vitamin E supplementation reduces markers of the inflammatory response in weaned pigs challenged with enterotoxigenic E.coli

Background： This experiment was conducted to test the hypothesis that vitamin E（Vit E） and acetylsalicylic acid（ASA）, a cyclooxygenase-2（COX-2） inhibitor, will additively reduce the production of the immunosuppressive molecule prostaglandin E_2（PGE_2） and hence reduce inflammatory responses in weaner pigs experimentally infected with an enterotoxigenic strain of E. coli.Methods： The experiment was conducted in a research facility with 192 individually-housed male weaner pigs（Landrace × Large White） weighing 6.6 ± 0.04 kg（mean ± SEM）. The pigs were experimentally infected with an enterotoxigenic strain of E. coli and were allocated to a 2 × 3 factorial design with the respective factors being without and with 125 ppm ASA and three levels of Vit E supplementation（50, 100 or 200 IU/kg diet, dl-α-tocopheryl acetate）.Results： Acetylsalicylic acid supplementation improved average daily gain（P 〈 0.05） and tended to improve feed：gain ratio（P 〈 0.10） during the first 14 d after weaning. Acetylsalicylic acid supplementation also improved（P 〈 0.001） amino acid utilization efficiency（as assessed by plasma urea level） and tended to decrease（P 〈 0.10） PGE2 production in the liver without affecting smal intestinal histology and tight junction protein mR NA expression in the jejunal epithelium. Vitamin E supplementation greater than 100 IU/kg diet sustained both the plasma Vit E concentration（P 〈 0.001） and plasma haptoglobin content（P 〈 0.001） after weaning. However, there was no additive effects of the combined supplementation of ASA and Vit E on performance, intestinal barrier function and inflammatory responses of weaned pigs.Conclusions： Although ASA and vitamin E improved amino acid utilization efficiency and reduced acute inflammatory responses, ASA and vitamin E did not additively reduce production of PGE2 and inflammatory responses in weaner pigs experimental y infected with an enterotoxigenic strain of E. coli.

Acetylsalicylic acid for metal stent in malignant distal common bile duct obstruction:A randomized controlled trial

Background:Endoscopic biliary drainage is the treatment of choice for patients with malignant distal common bile duct obstruction.Self-expandable metal stents have clinical advantages including an increased duration of patency that may be prolonged by acetylsalicylic acid(ASA)use.The aim of this study was to investigate whether ASA had a positive effect on the patency of self-expandable metal stents compared with placebo.Methods:This prospective,multicenter,double-blinded,and randomized placebo-controlled trial was conducted from October 2017 to May 2020 in Korea.Patients who underwent palliative endoscopic biliary drainage with self-expandable metal stents for malignant distal bile duct obstruction were enrolled,and allocated to ASA treatment or placebo.The study outcomes were the rate of stent dysfunction at 6 months,duration of stent patency,risk factors for stent dysfunction,and any adverse events.Results:Interim analysis included 24 and 28 patients in the ASA and placebo groups,respectively.There was no significant difference between the ASA and placebo groups in stent dysfunction(25.0%vs.20.7%,P=0.761)or the duration of stent patency(150.97±10.55 vs.158.07±8.70 days,P=0.497).Six patients experienced suspected ASA-related adverse events,and there was one lethal case.Conclusions:ASA did not prolong stent patency.This study was terminated early because of the possibility of serious adverse events related to ASA treatment of these patients receiving palliative care.

Acetylsalicylic acid interferes with embryonic kidney growth and development by a prostaglandin-independent mechanism

AIM To evaluate the effects of the non-selective, non-steroidal anti-infammatory drug （NSAID） acetylsalicylic acid （ASA）, on ex vivo embryonic kidney growth and development.METHODS Pairs of fetal mouse kidneys at embryonic day 12.5 were cultured ex vivo in increasing concentrations of ASA （0.04-0.4 mg/mL） for up to 7 d. One organ from each pair was grown in control media and was used as the internal control for the experimental contralateral organ. In some experiments, organs were treated with ASA for 48 h and then transferred either to control media alone or control media containing 10 μmol/L prostaglandin E2 （PGE2） for a further 5 d. Fetal kidneys were additionally obtained from prostaglandin synthase 2 homozygous null or heterozygous （PTGS2-/- and PTGS2-/＋） embryos and grown in culture. Kidney cross-sectional area was used to determine treatment effects on kidney growth. Whole-mount labelling to fluorescently detect laminin enabled crude determination of epithelial branching using confocal microscopy.RESULTSIncreasing ASA concentration （0.1, 0.2 and 0.4 mg/mL） significantly inhibited metanephric growth （P 〈 0.05）. After 7 d of culture, exposure to 0.2 mg/mL and 0.4 mg/mL reduced organ size to 53% and 23% of control organ size respectively （ P 〈 0.01）. Addition of 10 μmol/L PGE2 to culture media after exposure to 0.2 mg/mL ASA for 48 h resulted in a return of growth area to control levels. Application of control media alone after cessation of ASA exposure showed no benefit on kidney growth. Despite the apparent recovery of growth area with 10 μmol/L PGE2, no obvious renal tubular structures were formed. The number of epithelial tips generated after 48 h exposure to ASA was reduced by 40% （0.2 mg/mL; P 〈 0.05） and 47% （0.4 mg/mL; P 〈 0.01）. Finally, growth of PTGS2-/- and PTGS2＋/- kidneys in organ culture showed no differences, indicating that PTGS2 derived PGE2 may at best have a minor role.CONCLUSIONASA reduces early renal growth and development but the role of prostaglandins in this may be minor.

Acetylsalicylic Acid Administered in Patients with Type 2 Diabetes Mellitus and Its Effect on the Antioxidant Enzyme System

Type 2 diabetes mellitus and its complications are associated with oxidative stress and the depletion of antioxidant defenses. The influence of acetylsalicylic acid on reversing the decrease in antioxidants, insulin resistance, glucose homeostasis, and inflammatory cascade can help prevent diabetes complications. Purpose: The aim of the study was to evaluate the effect of acetylsalicylic acid on the antioxidant enzymatic system in patients with diabetes. Methods: A randomized, double-blind, placebo-controlled clinical trial was carried out in 21 patients of both sexes with Type 2 diabetes for less than five years at the time of diagnosis, without pharmacological treatment, and randomly selected. Acetylsalicylic acid (300 mg) was administered orally for three months to the study group (n = 11) compared to the placebo control group (n = 10). Before and after the intervention, anthropometric and metabolic measurements were taken, fasting plasma glucose, glycated hemoglobin A1c, lipid profile panel, glutathione peroxidase, superoxide dismutase, catalase, and antioxidant capacity/activity were determined;values are presented as mean ± standard deviation. Intra- and intergroup differences were tested by Wilcoxon signed rank and Mann-Whitney U test, respectively;p-value ≤ 0.05 was considered statistically significant. Results: The acetylsalicylic acid group showed a decrease in weight (85.6 ± 19.3 vs. 84.1 ± 19.0 kg p = 0.01), cholesterol (205.9 ± 16.6 vs. 186.0 ± 23.2 mg/dL p = 0.02), and glycated hemoglobin A1c (7.8% ± 0.9% vs. 7.0% ± 0.7% p = 0.02). The placebo group exhibited reduction in weight (76.1 ± 14.9 vs. 74.9 ± 15.0 kg p = 0.04), glycated hemoglobin A1c (6.9% ± 0.6% vs. 6.2% ± 0.4% p = 0.004), and total antioxidant capacity (4.1 ± 0.5 vs. 4.8 ± 0.3 mmol/L p = 0.002). Conclusion: The administration of acetylsalicylic acid did not modify the antioxidant enzyme system.

Trend Analysis of Combined Drugs Creation （for Example Acetylsalicylic Acid）

The pharmaceutical market of Ukraine in January 2015 was registered 71 drug based acetylsalicylic acid （ASA）, for which 52% combined. The most common combinations of ASA with acetaminophen and caffeine （45.9%）, magnesium hydroxide （18.9%）, bisoprolol （10.8%）, ascorbic acid （8.1%）, clopidogrel （5.4%）. Comparing markets combined drugs ASA of Ukraine, the Russian Federation, 28 EU countries, Norway, Switzerland, India, Syria, Australia and the USA identified the active pharmaceutical ingredients, combined with ASA in a single dosage form. The analysis of questionnaires 40 pharmacists pharmacies Temopil, Khmelnytsky and Kyiv regions of Ukraine noted that the biggest demand is mono-drugs ASA, Citramon, Askofen and Cardiomagnyl Methods of pharmacoeconomic studies proved efficient use Upsaryn UPSA with vitamin C tabl. spike, tuba in box number 20 BMS （France）, Citramon tablets number 6 PJSC ＂Monfarm＂ （Ukraine） and Cardiomagnyl tabl. film-coated shell 75 mg in bottle number 100 Nycomed Austria （Austria）. On the basis of six State Forms of drugs in Ukraine （2009-2014） was found that the combination of drugs based on ASA is recommended to use of ascorbic acid （Aspiryn C, Asprovit C, Upsarin UPSA with vitamin C）, dipyridamole （Agrenox）, magnesium hydroxide （Cardiomagnyl, Cardiomagnyl Forte）. Some of the standard combination of ASA （combination of paracetamol and caffeine） are not in form. For optimize State Form of drugs by improving health system in Ukraine can be useful pharmacoeconomic analysis of combination therapies with the current official system to note the combination of ASA with statins, esomeprazole, isosorbide.

Banana Peel for Acetylsalicylic Acid Retention

A method for adsorption involving banana peel (BP) was studied to remove the pollutant acetylsalicylic acid (ASA) in aqueous medium. The results show that bioadsorbent has satisfactory maximum adsorption capacity (2.29 mg/g) for removing this analgesic and anti-inflammatory drug in aqueous solution (pH 7.0) using the Langmuir mathematical model. The tested concentrations of this pollutant were higher than the levels commonly found in the aquatic environment. This and other results suggest the BP as an alternative to ASA removal in water contaminated with pharmaceuticals pollutants.

Characterization of a dextran–coated layered double hydroxide acetylsalicylic acid delivery system and its pharmacokinetics in rabbit

The aim of this study was to prepare a dextran–coated layered double hydroxide acetylsalicylic acid(DEX–LDH–ASA)delivery system by co-precipitation of LDH–ASA and its in-situ compositing with DEX.The structure of the system was investigated using X-ray diffraction(XRD),Fourier transform infrared spectroscopy(FT-IR)and thermogravimetry(TG).Its in vitro drug release properties and in vivo pharmacokinetics in rabbit were also determined.The results show that the DEX–LDH–ASA system retained the crystal structure of LDH–ASA and gave a marked improvement in its dispersion.It also prolonged the release of ASA and shifted the release pattern from first-order to zeroorder kinetics.The pharmacokinetics of ASA administered in the DEX–LDH–ASA system to rabbits produced two absorption peaks with a Cmax of 14.871.7 mg/L at 2.1170.69 h and an elimination halflife of 2.2570.84 h for the first peak.The fact that delivery of ASA in the DEX–LDH–ASA system was sustained with improved bioavailability indicates the potential of the system as a controlled release formulation with application to other drugs.

Preparation, Photo and Electroluminescence Properties of Novel Rare Earth Aromatic Carboxylates

Novel soluble rare earth aromatic carboxylates were prepared. The triplet energy level of organic ligand was measured. The photoluminescence properties of the Tb 3+ and Eu 3+ aromatic carboxylates and lifetimes were investigated, which indicated that these rare earth complexes have high quantum efficiency. Because of their excellent solubility, polymer-doping rare earth carboxylates were fabricated as thin films by spin-coating method and their luminescence properties were studied. Some rare earth organic light-emitting diodes were successfully fabricated which performed high pure color. The maximum luminance of the device of ITO/PVK/PVK∶Tb(AS) 3Phen∶PBD/PBD/Al is 32 cd·m -2 at 28 V.

Morphological characterization of metal porphyrin tailed with aspirin interacting with bovine serum albumin congeries

The porphyrins tailed with acetylsalicylic acid （ASA） and Zn （or Cu） complexes were prepared. Meanwhile, morphological images, such as shape and size of porphyrins-BSA congeries were observed by using atomic force microscopy （AFM）. The result showed the interaction of BSA and prepared porphyrins led to obvious change of shape and size of BSA congeries.

Rebamipide and Pantoprazole Combination in NSAIDs-Gastropathy Treatment

The objective of this study was to investigate the pantoprazole and rebamipide efficiency on NSAIDs （nonsteroidal anti-inflammatory drugs）-gastropathy restoring and healing in patients with coronary heart disease, stable angina, who have been taking aspirin for a long time period. The study included three groups of patients according to the treatment they have got： ASA （acetylsalicylic acid） in the first group; ASA and pantoprazole in the second; ASA, pantoprazole and rebamipide in the third one. To obtain the results, endoscopic method and proinflammatory cytokines LTB4 and protective prostaglandin E2 determination in the blood were used. The research demonstrated no ulcer effects in the group of patients who were treated by rebamipide, and significantly fewer gastroduodenal erosions, in comparison to the group, where treatment contained ASA and pantoprazole. The LTB4 （leukotriene B4） level decreased in pantoprazole and rebamipide treatment groups, but the PGE2 （prostaglandin E2） level increased only after rebamipide therapy. Therefore, rebamipide should be included to the therapy for the better NSAIDs-gastropathy treatment, in reason of its good reparative and gastroprotective properties.

Biodegradable Protection for Medical Devices with Medical Drugs Controlled Separation

With the aim of creating biodegradable materials for medical devices clinical appointments with high hemocompatibility we have developed a new polymer product.The basis of this product is plasticized by polyethylene glycol bacterial copolymer of hydroxybutyrate and oxovalerate. A well-known antitbrombotic supplement--acetylsalicylic acid has been added to improve hemocompatibility in the polymer. The results of our studies showed a controlled prolonged separation of acetylsalicylic acid from polymeric material in the blood. We studied in vitro the dynamics of liberation of acetylsalicylic acid from polymeric coatings. It was shown that the concentration of polyethylene glycol and the thickness of the polymer layer can affect the rate of diffusion of acetylsalicylic acid from polymer films.

Grafting of MIPs from PVDF Membranes via Reversible Addition-fragmentation Chain Transfer Polymerization for Selective Removal of p-Hydroxybenzoic Acid

Effective molecularly imprinted membranes（MIMs） were developed as an efficient adsorbent for the selective removal ofp-hydroxybenzoic acid（p-HB） from acetylsalicylic acid（ASA, aspirin）. The MIMs were grafted successfully from poly（vinylidene fluoride） microfiltration membranes via reversible addition-fragmentation chain transfer（RAFT） polymerization. The graft copolymerization of acrylic acid（AA） in the presence of template p-hydroxybenzoic acid led to molecularly imprinted polymer（MIP） film coated membranes. The obtained MIMs were characterized by scanning electron microscopy（SEM）, Fourier transform infrared spectrophotometer（FTIR） and Raman spectra, and batch mode adsorption studies were carried ont to investigate the specific adsorption equilibrium, kinetics and selective recognition properties of different MIMs. The kinetic properties of the MIMs could be well described by the pseudo-second-order rate equation. Selective permeation experiments were performed to evaluate the permeation selectivity of the p-HB imprinted membranes. The observed performances of the MIMs are applicable to the further purification of aspirin. Keywords Acetylsalicylic acid; Reversible addition-fragmentation chain transfer; Molecularly imprinted membrane; p-Hydroxybenzoic acid; Selective adsorption

Lysine acetylsalicylate ameliorates lung injury in rats acutely exposed to paraquat

Background Paraquat （PQ）, an effective and widely used herbicide, has been proven to be safe when appropriately applied to eliminate weeds. However, PQ poisoning is an extremely frustrating clinical condition with a high mortality and with a lack of effective treatments in humans. PQ mainly accumulates in the lung, and the main molecular mechanism of PQ toxicity is based on redox cycling and intracellular oxidative stress generation. The aim of this study was to evaluate whether lysine acetylsalicylate （LAS） could protect the lung from the damage of PQ poisoning and to study the mechanisms of protection. Methods A model of PQ poisoning was established in 75 Sprague-Dawley rats by intragastric administration of 50 mg/kg PQ, followed by treatment with 200 mg/kg of LAS. The rats were randomly divided into sham, PQ, and PQ＋LAS groups, with 25 in each group. We assessed and compared the malonaldehyde （MDA） content, superoxide dismutase activity （SOD）, glutathion peroxidase （GSH-Px）, and catalase （CAT） in serum and lung and the hydroxyproline （HYP） content, pathological changes, apoptosis and expression of Bcl-2/Bax protein in lung of rats on days 1, 3, 7, 14 and 21 after PQ poisoning and LAS treatment. Results Compared to the PQ group rats, early treatment with LAS reduced the MDA and HYP contents, and increased the SOD, GSH-Px, and CAT activities in the serum and lung on days 1, 3, 7, 14, and 21 after PQ poisoning （all P〈0.05）. After early LAS treatment, the apoptotic rate and Bax expression of lung decreased, the Bcl-2 expression increased, and the Bcl-2/Bax ratio increased, compared to the PQ group rats. Furthermore, the pathological results of lungs revealed that after LAS treatment, early manifestations of PQ poisoning, such as hemorrhage, edema and inflammatory-cell infiltration, were improved to some degree, and collagen fibers in the pulmonary interstitium were also obviously reduced. Conclusion In this rat model of PQ poisoning, LAS effectively ameliorated the lung injury induced by PQ, possibly through antioxidation, anti-fibrosis, anti-apoptosis, and anticoagulation.

The importance of timely diagnosis of aspirin-exacerbated respiratory disease for patient health and safety

Backgroud:Aspirin-exacerbated respiratory disease(AERD)is a difficult-to-treat syndrome where timely diagnosis and initiation of disease-specific therapies are pertinent to improved patient outcomes.Objective:To characterize the most common timeline for development of the clinical triad[asthma,nasal polyposis,and reactions to nonsteroidal anti-inflammatory drugs(NSAIDs)],identify barriers to prompt diagnosis of AERD,and describe indications for an aspirin challenge to facilitate accurate diagnosis.Methods:Six hundred ninety-seven patients with diagnosed AERD and history of at least one sinus surgery to remove nasal polyps were identified in the Brigham and Women’s Hospital AERD registry.Patient reported age at disease onset of asthma,nasal polyposis,and age of first NSAID reaction were obtained from 2013 to 2019 at enrollment.Results:Of the 697 patients identified,diagnosis of asthma preceded diagnosis of nasal polyposis and first NSAID reaction,although there was considerable variability between patients.Conclusions:Prompt diagnosis of AERD is important for patient and provider education and improved care of this difficult-to-treat population of patients.Consider diagnostic aspirin challenge in patients without historical reactions to NSAIDs who have an otherwise compatible clinical history,specifically in patients who take daily low-dose aspirin,leukotriene modifiers,avoid NSAIDs,or who are severely symptomatic at baseline where it would be difficult to identify an acute worsening of symptoms.