Psychotropic effects of aspirin, acetylsalicylate cobalt and acetylsalicylate zinc at various doses

For the first time it is shown that psychotropic action of acetylsalicylates at various doses is manifested as a nonmonotonic dependence having its peaks at therapeutic and ultra-low dose zones. It is discovered that development of effects of aspirin resembles that of acetylsalicylate zinc. Acetylsalicylate cobalt at extremely low doses zone showed the highest antidepressant activity, demonstrating toxicity at high doses. Generally, it is revealed that the use of aspirin and its salts at high doses range causes maximum psychotropic effects development, usually accompanied by side-effects. Therefore, aspirin, acetylsalicylate cobalt and zinc at extremely low doses are recommended for further study as psychotropic medications.

Stability Studies of Lysine Acetylsalicylate(Aspirin Derivative):Mechanisms of Hydrolysis

To control the stability of the lysine acetylsalicylate compound (LAS) in aqueous solution, some studies of the hydronium ion-catalyzed, hydroxide ion-catalyzed, and spontaneous reactions of this active ingredient in water solutions have been carried out. The pH-rate profile (log kobs = f(pH)), shows that the hydrolysis reaction of the LAS, is conducted by a catalysis acid-base mechanism, with multiple reaction pathways. The rate constants, kH, kOH and k0 to the reaction pathways catalyzed by H3O+, HO– ions and to the spontaneous reaction, for the hydrolysis reaction of the reagent LAS, were determined. The results show that the studied compound LAS is unstable in basic medium and the hydrolysis reaction catalyzed by HO– ions is predominant.For a known acidity (pH ≈ 10), studies conducted for different temperatures of the medium, clearly indicate, that the experimental rate constant kobs,depends on the temperature according to the Arrhenius equation. The activation parameters: activation energy (Ea), enthalpy (ΔH≠) and entropy (ΔS≠), for the transition state were determined, The very negative value obtained for the activation parameter ΔS*, first indicates that in the transition state there is gain in order, then this late state, resembles the products and that probably for the mechanism of the LAS hydrolysis reaction catalyzed by HO– ions, the rate-determining step is a bimolecular reaction. Finally from all these results, the mechanism for the reaction pathway catalyzed by HO– ions has been elucidated.

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.

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.

Growth Inhibition Effect of DL-Lysine Acetylalicylate on sw480 Colon Carcinoma Cells

Objective： To investigate the effect of DL-lysine acetylsalicylate on proliferation of colon carcinoma cells line sw480. Methods： After treatment of DL-lysine acetylsalicylate, the study was performed by observing sw480 colorectal cancer cells with phase contrast microscope, making growth curve, and examining the inhibition rate of sw480 cells with MTT assay. Results： The morphology of sw480 cells showed characteristics of apoptosis, the cell growth curve showed inhibited proliferation of sw480 cells when treated with DL-lysine acetylsalicylate （P〈0.05）. The rate of inhibition was upward when the drug concentration increased. Conclusion： DL-lysine acetylsalicylate for injection can inhibit the growth of sw480 colorectal cancer cells obviously in a dose dependent manner.

Risk factors associated with the development of ischemic colitis

AIM:To ascertain the role of cardiovascular risk factors,cardiovascular diseases,standard treatments and other diseases in the development of ischemic colitis(IC).METHODS:A retrospective,case-control study was designed,using matched data and covering 161 incident cases of IC who required admission to our hospital from 1998 through 2003.IC was diagnosed on the basis of endoscopic findings and diagnostic or compatible his-tology.Controls were randomly chosen from a cohort of patients who were admitted in the same period and required a colonoscopy,excluding those with diagnosis of colitis.Cases were matched with controls(ratio 1:2),by age and sex.A conditional logistic regression was performed.RESULTS:A total of 483 patients(161 cases,322 con-trols)were included;mean age 75.67±10.03 years,55.9%women.The principal indications for colonos-copy in the control group were lower gastrointestinal hemorrhage(35.4%),anemia(33.9%),abdominal pain(19.9%)and diarrhea(9.6%).The endoscopic findings in this group were hemorrhoids(25.5%),diverticular disease(30.4%),polyps(19.9%)and colorectal cancer(10.2%).The following variables were associated with IC in the univariate analysis:arterial hypertension(P= 0.033);dyslipidemia(P<0.001);diabetes mellitus(P =0.025);peripheral arterial disease(P=0.004);heart failure(P=0.026);treatment with hypotensive drugs(P=0.023);angiotensin-converting enzyme inhibitors;(P=0.018);calcium channel antagonists(P=0.028);and acetylsalicylic acid(ASA)(P<0.001).Finally,the following variables were independently associated with the development of IC:diabetes mellitus[odds ratio(OR)1.76,95%confidence interval(CI):1.001-3.077,P=0.046];dyslipidemia(OR 2.12,95%CI:1.26-3.57,P=0.004);heart failure(OR 3.17,95%CI:1.31-7.68,P=0.01);peripheral arterial disease(OR 4.1,95%CI:1.32-12.72,P=0.015);treatment with digoxin(digitalis)(OR 0.27,95%CI:0.084-0.857,P=0.026);and ASA(OR 1.97,95%CI:1.16-3.36,P=0.012).CONCLUSION:The development of an episode of IC was independently associated with diabetes,dyslipid-emia,presence of heart failure,peripheral arterial dis-ease and treatment with digoxin or ASA.

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.

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.

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.

Aspirin plus Pseudoephedrine (Aspirin Complex) for the Treatment of Symptoms of Upper Respiratory Tract Infection

Upper respiratory tract infections or common colds are a multi-symptom disease which is usually symptomatically treated with fixed dose multi-active ingredient medicinal products which are commonly used as non-prescription and over the counter. However, the active ingredients combined require a particular and clinically sound justification. Analgesics and decongestant can be combined to treat simultaneously the prominent symptoms cold-related pain (e.g. headache, muscle aches and pains), fever, inflammationand nasal/sinus congestion. This overview provides a summary of the evidence supporting the combination of acetylsalicylic acid (aspirin) and pseudoephedrine available in the common cold product Aspirin? Complex.

Hot-melt sub-and outercoating combined with enteric aqueous coating to improve the stability of aspirin tablets

Aspirin is apt to hydrolyze. In order to improve its stability, a new method has been developed involving the application of hot-melt sub-and outercoating combined with enteric aqueous coating. The main aim was to investigate the influence of these factors on the stability of ASA and understand how they work. Satisfactory storage stability were obtained when the aspirin tablet core coated with Eudragit L30D55 film was combined with glycerin monostearate(GMS) as an outercoat. Hygroscopicity testing indicated that the moisture penetrating into the tablet may result in a significant change in the physical properties of the coating film observed by scanning electron microscopy. Investigation of the compatibility between the drug and film excipients shows that the talc and methacrylic acid had a significant catalytic effect on ASA. A hypothesis was proposed that the hydrolysis of ASA enteric coated tablets(ASA-ECT) was mostly concentrated in the internal film and the interfaces between the film and tablet core. In conclusion, hot-melt coating technology is an alternative to subcoating or outercoating. Also, GMS sub-coating was a better choice for forming a stable barrier between the tablet core and the polymer coating layer, and increases the structure and chemical stability.

Effect of graded doses of acetylsalicylic acid on sperm chromatin integrity and maturity of germinal epithelium in adult male mouse

Objective:To evaluate the effect of graded doses of acetylsalicylic acid (ASA) on sperm chromatin integrity and sex hormones in the adult male mouse.Methods:Forty-nine male adult mice were divided into seven groups. Control group received no drug, sham group received ASA solvent (dimethylsulfoxide 0.1%), groups 3 to 7 received different doses of 0.05, 0.10, 0.50, 1.00 and 5.00 mg ASA, daily for 14 d, respectively. On day 15, evaluations were made by sperm chromatin dispersion test for the study of DNA sperm integrity, radioimmunoassay for the study of testosterone and luteinizing hormone (LH) level and histopathology of testis for Jhonson's scoring.Results: ASA in groups 0.50, 1.00 and 5.00 mg reduced big halo sperms. DNA fragmentation significantly increased just in 5 mg group. Serum level of testosterone in doses of 0.50, 1.00 and 5.00 mg groups reduced significantly (P<0.01) while LH level was not affected. Johnson's score reduced in all ASA treated groups.Conclusions: Administration of ASA over the 14 days in dose of 5.00 mg increases sperm DNA fragmentation index and therefore reduces DNA integrity and in doses of 0.50, 1.00, 5.00 mg reduces serum testosterone level with no effect on LH. Generally, ASA has deleterious effects on the male reproductive indices even in low doses.

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.

Modifying action of heavy metal salts on an-ti-inflammatory aspirin action

Nowadays pollution of the environment is one of the major problems of mankind. Moreover, studying of the effect of different kinds of med- icine on selected, specially bred, non-exposed to external pollutants animals is becoming distant from reality. Thus in this work we have investigated the modifying action of heavy metals on anti-inflammatory effect of aspirin. The investigation were carried out on rats which were injected during 7 days intraperitoneally by PbCl3, HgCl2, CdCl2 in concentration of 100, 20, 1 mg/kg accordingly, modulating accumulation of the metals in the organism tissues. On the 8 days inflammation was invoked by formalin. As anti-inflammatory medicine was use aspirin. Judging by obtained results the conclusion can be drawn that cadmium in concentration 1 mg/kg significantly increases anti-inflammatory aspirin activity. The observed outcome can be explained in the following way. It is generally known that zinc in a certain concentration demonstrates anti-inflammatory properties. Be- ing an element of the same group cadmium has similar properties and also can have anti-inflammatory action. Lead and mercury suppre- ssed anti-inflammatory aspirin activity. Obvious inhibitory action of mercury and lead salts on aspirin action related to the fact that these elements by themselves were inflammation factors. From the obtained results the following conclusion can be drawn: a definite dose of anti-inflammatory medicine (aspirin) which is sufficient in normal conditions became less effective against the background of accumulation of ions of some heavy metals in an organism.

The Antihypertensive Effect of ASA Lasts Less than 24 Hours?

Objectives: Some studies suggest that acetylsalicylic acid (ASA) administered in the evening may have a lowering effect on the blood pressure. The purpose of this study was to measure the effect of the time of ASA administration on blood pressure, markers of arterial stiffness as well as various plasma parameters. Methods and Results: The study included 34 patients (20 men and 14 women) ranging in age from 47 to 82 years. Low-dose ASA (50 - 250 mg/day) was used by all the patients, first in the morning and later in the evening for three months. Home, office and ambulatory blood pressure and pulse wave velocity (PWV) were measured. Compared with the morning administration of ASA, significantly lower office systolic blood pressure (p = 0.017) and significantly higher carotid-femoral PWV (p = 0.010) as well as plasma triglycerides (p = 0.002) were found after the evening administration. There were no statistically significant changes in the average ambulatory blood pressure values, carotid-radial PWV or other parameters measured. However, the time of ASA administration seemed to affect the circadian variation in blood pressure. Conclusions: The results suggest that ASA administration may lower blood pressure, but for less than 24 hours. Our results should be verified by larger, randomized studies.

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.

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.

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.