Degradation of paracetamol in aqueous solutions by TiO2 photocatalysis.

Science.gov (United States)

Yang, Liming; Yu, Liya E; Ray, Madhumita B

2008-07-01

In this study, photo/photocatalytic oxidation of common analgesic and antipyretic drug, paracetamol (acetaminophen), was investigated to determine the optimal operating conditions for degradation in water. UVA (365 nm) radiation alone degraded negligible amount of paracetamol, whereas paracetamol concentration decreased substantially under an irradiation of UVC (254 nm) with marginal changes in total organic carbon (TOC). In the presence of TiO2, much faster photodegradation of paracetamol and effective mineralization occurred; more than 95% of 2.0mM paracetamol was degraded within 80 min. The degradation rate constant decreased with an increase in the initial concentration of paracetamol, while it increased with light intensity and oxygen concentration. The degradation rate also increased with TiO2 loading until a concentration of 0.8 g L(-1). The degradation rate slowly increased between pH 3.5 and 9.5, but significantly decreased with increasing pH between 9.5 and 11.0. Based on the experimental data, a kinetic equation describing paracetamol photocatalytic degradation with various process parameters is obtained.

Saliva with reduced calcium and phosphorous concentrations: Effect on erosion dental lesions.

Science.gov (United States)

Denucci, Giovanna Corrêa; Mantilla, Taís Fonseca; Amaral, Flávia Lucisano Botelho; Basting, Roberta Tarkany; França, Fabiana Mantovani Gomes; Turssi, Cecilia Pedroso

2018-02-08

To investigate whether saliva formulations with reduced calcium (Ca) and inorganic phosphorous (Pi) concentration would affect dental erosion caused by hydrochloric acid (HCl). Enamel and root dentine bovine slabs were embedded, polished and measured for surface Knoop microhardness (SMH). After reference areas were created, specimens were exposed to HCl solution (0.01M; pH 2; 120s) and immersed in artificial salivas (6h) containing three different Ca/Pi concentrations (n=15), which simulate serum conditions of normo-, mild- or severe hypocalcaemia. The control group was immersed in Ca/Pi-free saliva. The study protocol was carried out 2x/day for 5 days. Surface loss of enamel and root dentine was assessed using an optical profilometer and SMH was remeasured for enamel. ANOVA (pdental substrate, salivary formulations resembling serum hypocalcaemia affected surface loss due to erosion and rehardening thereof. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Time-related Changes in pH, Buffering Capacity and Phosphate and Urea Concentration of Stimulated Saliva.

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Vuletic, Lea; Peros, Kristina; Spalj, Stjepan; Rogic, Dunja; Alajbeg, Ivan

2014-01-01

To quantify changes in pH, buffering capacity and hydrogen carbonate, phosphate, protein and urea concentrations of stimulated saliva which occur during a 30-min measurement delay after saliva collection. The correlation between time-related chemical changes and changes of salivary pH and buffering capacity was assessed in order to explain the observed changes in salivary pH and buffering capacity. Stimulated saliva samples were collected from 30 volunteers after inducing salivation by chewing a piece of parafilm. Measurements of salivary variables were made immediately after saliva collection and again 30 min later, during which time the specimens were exposed to the atmosphere in collection cups at room temperature. Postponement of measurements resulted in a significant increase in pH and a significant decrease of buffering capacity, phosphate and urea concentration. The results suggest that the time-related pH increase could primarily be attributed to loss of dissolved carbon dioxide from saliva, and confirm the importance of hydrogen carbonate in the neutralisation of hydrogen ions, but they do not support the principle of catalysed phase-buffering for the hydrogen carbonate buffer system in saliva. A decrease in phosphate and urea concentration affects salivary buffering capacity. This study emphasises the importance of the standardisation of measurement time when measuring salivary pH, buffering capacity, phosphate and urea concentrations following the collection of saliva in order to obtain comparable results. It also provides a partial explanation of the mechanisms underlying the observed changes of pH and buffering capacity over time.

Interaction of paracetamol and 125I-paracetamol with surface groups of activated carbon. Theoretical and experimental study

International Nuclear Information System (INIS)

Daniel Hernandez-Valdes; Ulises Jauregui-Haza; Carlos Enriquez-Victorero; Melvin Arias

2015-01-01

The selection of activated carbon (AC) filters for water decontamination is currently carried out empirically. The low concentrations of drugs in the environment make the radioisotope labeling a valuable tool for physical and chemical studies of the adsorption process. A theoretical study of paracetamol and 125 I-paracetamol adsorption onto AC was performed to evaluate the interactions between pollutants and surface groups (SG) of AC. Paracetamol was labeled with 125 I and adsorption isotherms were obtained using radioanalytical and spectrophotometric techniques. The radioanalytical method overestimates the paracetamol adsorption. The validity of the chosen approach for qualitative assessment of SG influence over the adsorption process was demonstrated. (author)

Overdose pattern and outcome in paracetamol-induced acute severe hepatotoxicity

Science.gov (United States)

Craig, Darren G N; Bates, Caroline M; Davidson, Janice S; Martin, Kirsty G; Hayes, Peter C; Simpson, Kenneth J

2011-01-01

AIMS Paracetamol (acetaminophen) hepatotoxicity is the commonest cause of acute liver failure (ALF) in the UK. Conflicting data regarding the outcomes of paracetamol-induced ALF resulting from different overdose patterns are reported. METHODS Using prospectively defined criteria, we have analysed the impact of overdose pattern upon outcome in a cohort of 938 acute severe liver injury patients admitted to the Scottish Liver Transplantation Unit. RESULTS Between 1992 and 2008, 663 patients were admitted with paracetamol-induced acute severe liver injury. Of these patients, 500 (75.4%) had taken an intentional paracetamol overdose, whilst 110 (16.6%) had taken an unintentional overdose. No clear overdose pattern could be determined in 53 (8.0%). Unintentional overdose patients were significantly older, more likely to abuse alcohol, and more commonly overdosed on compound narcotic/paracetamol analgesics compared with intentional overdose patients. Unintentional overdoses had significantly lower admission paracetamol and alanine aminotransferase concentrations compared with intentional overdoses. However, unintentional overdoses had greater organ dysfunction at admission, and subsequently higher mortality (unintentional 42/110 (38.2%), intentional 128/500 (25.6%), P paracetamol overdose is associated with increased mortality compared with intentional paracetamol overdose, despite lower admission paracetamol concentrations. Alternative prognostic criteria may be required for unintentional paracetamol overdoses. PMID:21219409

Paracetamol as a Post Prandial Marker for Gastric Emptying, A Food-Drug Interaction on Absorption.

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R Bartholomé

Full Text Available The use of paracetamol as tool to determine gastric emptying was evaluated in a cross over study. Twelve healthy volunteers were included and each of them consumed two low and two high caloric meals. Paracetamol was mixed with a liquid meal and administered by a nasogastric feeding tube. The post prandial paracetamol plasma concentration time curve in all participants and the paracetamol concentration in the stomach content in six participants were determined. It was found that after paracetamol has left the stomach, based on analysis of the stomach content, there was still a substantial rise in the plasma paracetamol concentration time curve. Moreover, the difference in gastric emptying between high and low caloric meals was missed using the plasma paracetamol concentration time curve. The latter curves indicate that (i part of the paracetamol may leave the stomach much quicker than the meal and (ii part of the paracetamol may be relatively slowly absorbed in the duodenum. This can be explained by the partition of the homogenous paracetamol-meal mixture in the stomach in an aqueous phase and a solid bolus. The aqueous phase leaves the stomach quickly and the paracetamol in this phase is quickly absorbed in the duodenum, giving rise to the relatively steep increase of the paracetamol concentration in the plasma. The bolus leaves the stomach relatively slowly, and encapsulation by the bolus results in relatively slow uptake of paracetamol from the bolus in the duodenum. These findings implicate that paracetamol is not an accurate post prandial marker for gastric emptying. The paracetamol concentration time curve rather illustrates the food-drug interaction on absorption, which is not only governed by gastric emptying.ClinicalTrials.gov NCT01335503 Nederlands Trial Register NTR2780.

Degradation of paracetamol by pure bacterial cultures and their microbial consortium.

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Zhang, Lili; Hu, Jun; Zhu, Runye; Zhou, Qingwei; Chen, Jianmeng

2013-04-01

Three bacterial strains utilizing paracetamol as the sole carbon, nitrogen, and energy source were isolated from a paracetamol-degrading aerobic aggregate, and assigned to species of the genera Stenotrophomonas and Pseudomonas. The Stenotrophomonas species have not included any known paracetamol degraders until now. In batch cultures, the organisms f1, f2, and fg-2 could perform complete degradation of paracetamol at concentrations of 400, 2,500, and 2,000 mg/L or below, respectively. A combination of three microbial strains resulted in significantly improved degradation and mineralization of paracetamol. The co-culture was able to use paracetamol up to concentrations of 4,000 mg/L, and mineralized 87.1 % of the added paracetamol at the initial of 2,000 mg/L. Two key metabolites of the biodegradation pathway of paracetamol, 4-aminophenol, and hydroquinone were detected. Paracetamol was degraded predominantly via 4-aminophenol to hydroquinone with subsequent ring fission, suggesting new pathways for paracetamol-degrading bacteria. The degradation of paracetamol could thus be performed by the single isolates, but is stimulated by a synergistic interaction of the three-member consortium, suggesting a possible complementary interaction among the various isolates. The exact roles of each of the strains in the consortium need to be further elucidated.

Degradation of paracetamol by Pseudomonas aeruginosa strain HJ1012.

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Hu, Jun; Zhang, Li L; Chen, Jian M; Liu, Yu

2013-01-01

Pseudomonas aeruginosa strain HJ1012 was isolated on paracetamol as a sole carbon and energy source. This organism could completely degrade paracetamol as high as 2200 mg/L. Following paracetamol consumption, a CO₂ yield rate up to 71.4% proved that the loss of paracetamol was mainly via mineralization. Haldane's equation adequately described the relationship between the specific growth rate and substrate concentration. The maximum specific growth rate and yield coefficient were 0.201 g-Paracetamol/g-VSS·h and 0.101 mg of biomass yield/mg of paracetamol consumed, respectively. A total of 8 metabolic intermediates was identified and classified into aromatic compounds, carboxylic acids, and inorganic species (nitrite and nitrate ions). P-aminophenol and hydroquinone are the two key metabolites of the initial steps in the paracetamol catabolic pathway. Paracetamol is degraded predominantly via p-aminophenol to hydroquinone with subsequent ring fission, suggesting partially new pathways for paracetamol-degrading bacteria.

Pharmacokinetics of paracetamol in chicks treated with metronidazole

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S.M. Hussain

2017-06-01

Full Text Available Effect of metronidazole on the pharmacokinetics of paracetamol were examined in chicks. Chicks were dosed orally with metronidazole at 350 mg\\kg of body weight daily (10 -13 days of age. On the last day of metronidazole dosing, chicks injected intraperitoneally with paracetamol at of 50 mg\\kg of body weight. Paracetamol appeared in chick plasma at 52.00, 45.00, 40.75, 32.75, 23.25 µg \\ml after 0.25, 0.50, 0.75, 1, 2, 4 hours of injection respectively. A significantly decreased the concentration paracetamol at times of 0.25, 0.50, 0.75, 1, 4 hours post injection and appeared at concentrations of 36.62, 35.37, 25.62, 20.50, 11.00 µg\\ml. These was reflected by changes in the pharmacokinetics of paracetamol as show by the increase elimination rate constant (48% and decrease in the half-life (32 % and increase in volume distribution (29% and increase in clearance by (96% and decrease in the area under the plasma curve (33% and decrease in the area under moment curve 65% and lack mean residence time (33%. These results indicate that oral dosing of chicks with metronidazole for four consecutive days and this effect increase in the elemination rate of paracetamol and this effect must be considered when therapy with paracetamol when given during metronidazole therapy.

Novel atomic absorption spectrometric and rapid spectrophotometric methods for the quantitation of paracetamol in saliva: application to pharmacokinetic studies.

Science.gov (United States)

Issa, M M; Nejem, R M; El-Abadla, N S; Al-Kholy, M; Saleh, Akila A

2008-01-01

A novel atomic absorption spectrometric method and two highly sensitive spectrophotometric methods were developed for the determination of paracetamol. These techniques based on the oxidation of paracetamol by iron (III) (method I); oxidation of p-aminophenol after the hydrolysis of paracetamol (method II). Iron (II) then reacts with potassium ferricyanide to form Prussian blue color with a maximum absorbance at 700 nm. The atomic absorption method was accomplished by extracting the excess iron (III) in method II and aspirates the aqueous layer into air-acetylene flame to measure the absorbance of iron (II) at 302.1 nm. The reactions have been spectrometrically evaluated to attain optimum experimental conditions. Linear responses were exhibited over the ranges 1.0-10, 0.2-2.0 and 0.1-1.0 mug/ml for method I, method II and atomic absorption spectrometric method, respectively. A high sensitivity is recorded for the proposed methods I and II and atomic absorption spectrometric method value indicate: 0.05, 0.022 and 0.012 mug/ml, respectively. The limit of quantitation of paracetamol by method II and atomic absorption spectrometric method were 0.20 and 0.10 mug/ml. Method II and the atomic absorption spectrometric method were applied to demonstrate a pharmacokinetic study by means of salivary samples in normal volunteers who received 1.0 g paracetamol. Intra and inter-day precision did not exceed 6.9%.

Improving degradation of paracetamol by integrating gamma radiation and Fenton processes.

Science.gov (United States)

Cruz-González, Germán; Rivas-Ortiz, Iram B; González-Labrada, Katia; Rapado-Paneque, Manuel; Chávez-Ardanza, Armando; Nuevas-Paz, Lauro; Jáuregui-Haza, Ulises J

2016-10-14

Degradation of paracetamol (N-(4-hydroxiphenyl)acetamide) in aqueous solution by gamma radiation, gamma radiation/H2O2 and gamma radiation/Fenton processes was studied. Parameters affecting the radiolysis of paracetamol such as radiation dose, initial concentration of pollutant, pH and initial oxidant concentration were investigated. Gamma radiation was performed using a (60)Co source irradiator. Paracetamol degradation and mineralization increased with increasing absorbed radiation dose, but decreased with increasing initial concentration of the drug in aqueous solution. The addition of H2O2 resulted in an increased effect on irradiation-driven paracetamol degradation in comparison with the performance of the irradiation-driven process alone: paracetamol removal increased from 48.9% in the absence of H2O2 to 95.2% for H2O2 concentration of 41.7 mmol/L. However, the best results were obtained with gamma radiation/Fenton process with 100% of the drug removal at 5 kGy, for optimal H2O2 and Fe(2+) concentrations at 13.9 and 2.3 mmol/L, respectively, with a high mineralization of 63.7%. These results suggest gamma radiation/H2O2 and gamma radiation/Fenton processes as promising methods for paracetamol degradation in polluted wastewaters.

Understanding lactic acidosis in paracetamol (acetaminophen) poisoning.

Science.gov (United States)

Shah, Anoop D; Wood, David M; Dargan, Paul I

2011-01-01

Paracetamol (acetaminophen) is one of the most commonly taken drugs in overdose in many areas of the world, and the most common cause of acute liver failure in both the UK and USA. Paracetamol poisoning can result in lactic acidosis in two different scenarios. First, early in the course of poisoning and before the onset of hepatotoxicity in patients with massive ingestion; a lactic acidosis is usually associated with coma. Experimental evidence from studies in whole animals, perfused liver slices and cell cultures has shown that the toxic metabolite of paracetamol, N-acetyl-p-benzo-quinone imine, inhibits electron transfer in the mitochondrial respiratory chain and thus inhibits aerobic respiration. This occurs only at very high concentrations of paracetamol, and precedes cellular injury by several hours. The second scenario in which lactic acidosis can occur is later in the course of paracetamol poisoning as a consequence of established liver failure. In these patients lactate is elevated primarily because of reduced hepatic clearance, but in shocked patients there may also be a contribution of peripheral anaerobic respiration because of tissue hypoperfusion. In patients admitted to a liver unit with paracetamol hepatotoxicity, the post-resuscitation arterial lactate concentration has been shown to be a strong predictor of mortality, and is included in the modified King's College criteria for consideration of liver transplantation. We would therefore recommend that post-resuscitation lactate is measured in all patients with a severe paracetamol overdose resulting in either reduced conscious level or hepatic failure. © 2010 The Authors. British Journal of Clinical Pharmacology © 2010 The British Pharmacological Society.

Pharmacokinetic drug-drug interaction between erlotinib and paracetamol: A potential risk for clinical practice.

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Karbownik, Agnieszka; Szałek, Edyta; Sobańska, Katarzyna; Grabowski, Tomasz; Wolc, Anna; Grześkowiak, Edmund

2017-05-01

Erlotinib is a tyrosine kinase inhibitor available for the treatment of non-small cell lung cancer. Paracetamol is an analgesic agent, commonly used in cancer patients. Because these drugs are often co-administered, there is an increasing issue of interaction between them. The aim of the study was to investigate the effect of paracetamol on the pharmacokinetic parameters of erlotinib, as well as the influence of erlotinib on the pharmacokinetics of paracetamol. The rabbits were divided into three groups: the rabbits receiving erlotinib (I ER ), the group receiving paracetamol (II PR ), and the rabbits receiving erlotinib+paracetamol (III ER+PR ). A single dose of erlotinib was administered orally (25mg) and was administered intravenously (35mg/kg). Plasma concentrations of erlotinib, its metabolite (OSI420), paracetamol and its metabolites - glucuronide and sulphate were measured with the validated method. During paracetamol co-administration we observed increased erlotinib maximum concentration (C max ) and area under the plasma concentration-time curve from time zero to infinity (AUC 0-∞ ) by 87.7% and 31.1%, respectively. In turn, erlotinib lead to decreased paracetamol AUC 0-∞ by 35.5% and C max by 18.9%. The mean values of paracetamol glucuronide/paracetamol ratios for C max were 32.2% higher, whereas paracetamol sulphate/paracetamol ratios for C max and AUC 0-∞ were 37.1% and 57.1% lower in the II PR group, when compared to the III ER+PR group. Paracetamol had significant effect on the enhanced plasma exposure of erlotinib. Additionally, erlotinib contributed to the lower concentrations of paracetamol. Decreased glucuronidation and increased sulphation of paracetamol after co-administration of erlotinib were also observed. Copyright © 2017. Published by Elsevier B.V.

Adrenal status assessed by direct radioimmunoassay of cortisol in whole saliva or parotid saliva

International Nuclear Information System (INIS)

Walker, R.F.; Riad-Fahmy, D.; Read, G.F.

1978-01-01

We describe a direct radioimmunoassay for cortisol in 10-μl volumes of parotid saliva or whole saliva. Binding proteins are absent from these fluids, as demonstrated by the excellent correlation between results for samples assayed directly and by a comparison procedure involving extraction with 1,2-dichloroethane. The direct assay is specific, precise, and had a lower limit of sensitivity of 4 pg per assay tube. Comparison of cortisol concentrations in plasma, parotid saliva, and whole saliva in persons undergoing investigations for assessing adrenal function, including stimulation with cosyntropin (Synachthen) and suppression with dexamethasone, indicated that changes in plasma cortisol concentration were accurately and immediately reflected in saliva from either the parotid-gland or whole saliva. A marked circadian rhythm has also been demonstrated for cortisol in parotid-gland saliva and whole saliva. We had to modify the 1,2-dichloroethane extraction procedure for accurate determination of cortisol in parotid saliva and whole saliva of patients undergoing treatment with metyrapone

Risk prediction of hepatotoxicity in paracetamol poisoning.

Science.gov (United States)

Wong, Anselm; Graudins, Andis

2017-09-01

Paracetamol (acetaminophen) poisoning is the most common cause of acute liver failure in the developed world. A paracetamol treatment nomogram has been used for over four decades to help determine whether patients will develop hepatotoxicity without acetylcysteine treatment, and thus indicates those needing treatment. Despite this, a small proportion of patients still develop hepatotoxicity. More accurate risk predictors would be useful to increase the early detection of patients with the potential to develop hepatotoxicity despite acetylcysteine treatment. Similarly, there would be benefit in early identification of those with a low likelihood of developing hepatotoxicity, as this group may be safely treated with an abbreviated acetylcysteine regimen. To review the current literature related to risk prediction tools that can be used to identify patients at increased risk of hepatotoxicity. A systematic literature review was conducted using the search terms: "paracetamol" OR "acetaminophen" AND "overdose" OR "toxicity" OR "risk prediction rules" OR "hepatotoxicity" OR "psi parameter" OR "multiplication product" OR "half-life" OR "prothrombin time" OR "AST/ALT (aspartate transaminase/alanine transaminase)" OR "dose" OR "biomarkers" OR "nomogram". The search was limited to human studies without language restrictions, of Medline (1946 to May 2016), PubMed and EMBASE. Original articles pertaining to the theme were identified from January 1974 to May 2016. Of the 13,975 articles identified, 60 were relevant to the review. Paracetamol treatment nomograms: Paracetamol treatment nomograms have been used for decades to help decide the need for acetylcysteine, but rarely used to determine the risk of hepatotoxicity with treatment. Reported paracetamol dose and concentration: A dose ingestion >12 g or serum paracetamol concentration above the treatment thresholds on the paracetamol nomogram are associated with a greater risk of hepatotoxicity. Paracetamol elimination half

Recommendations for the paracetamol treatment nomogram and side effects of N-acetylcysteine

NARCIS (Netherlands)

Koppen, A.; van Riel, A.; de Vries, I.; Meulenbelt, J.

2014-01-01

Treatment of paracetamol intoxication consists of administration of N-acetylcysteine, preferably shortly after paracetamol ingestion. In most countries, the decision to treat patients with N-acetylcysteine depends on the paracetamol plasma concentration. In the literature, different arguments are

[Paracetamol (acetaminophen) use in neonatology: a (re)appreciation of an old drug].

Science.gov (United States)

Langhendries, J-P

2015-10-01

In neonates, paracetamol is mainly used for its analgesic action. This drug is actually preferred by neonatologists because of its broad therapeutic index. Recently, it has been demonstrated that paracetamol is also an anti-cyclooxygenase (COX) medication through its inhibitory action on the peroxidase arm of central and peripheral COX (Boutaud et al., 2002; Toussaint et al., 2010; Graham et al., 2013; Hinz et al., 2008; Hinz and Brune, 2011). As such, this drug interferes with the synthesis of prostaglandins. This inhibition of peroxidase is, however, limited to a low concentration of arachidonic acid (AA) (around 2μM, in vitro) when the plasmatic concentration of paracetamol is experimentally 10μM, actually within the same range as compared to the therapeutic concentrations in vivo. This may partly explain its low anti-inflammatory effect as compared to ibuprofen and indomethacin, which exert their inhibition on COX whatever the AA concentrations are. This new well-demonstrated action of paracetamol on peripheral COX-2 of intact cells could explain recent observations making this drug a potential alternative in treating patent ductus arteriosus. However, the higher dosages that have been claimed by some authors in this indication still remain to be validated. This inhibition that paracetamol shows on the physiological synthesis of prostaglandins E2 (PGE2) could also explain some long-term immune deviations because the physiological concentration of PGE2 is a well-known actor in the genesis of immune homeostasis in the submucosal area. Indeed, recent epidemiology studies have pointed out immune deviations in children repeatedly exposed to paracetamol earlier in life. Consequently, this is actually the new discovery of an old drug. From these new data on paracetamol, a more focused pharmacovigilance on the long-term effects of paracetamol repeatedly given in the early stage should be urgently initiated. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Enhanced degradation of paracetamol by UV-C supported photo-Fenton process over Fenton oxidation.

Science.gov (United States)

Manu, B; Mahamood, S

2011-01-01

For the treatment of paracetamol in water, the UV-C Fenton oxidation process and classic Fenton oxidation have been found to be the most effective. Paracetamol reduction and chemical oxygen demand (COD) removal are measured as the objective functions to be maximized. The experimental conditions of the degradation of paracetamol are optimized by the Fenton process. Influent pH 3, initial H(2)O(2) dosage 60 mg/L, [H(2)O(2)]/[Fe(2+)] ratio 60 : 1 are the optimum conditions observed for 20 mg/L initial paracetamol concentration. At the optimum conditions, for 20 mg/L of initial paracetamol concentration, 82% paracetamol reduction and 68% COD removal by Fenton oxidation, and 91% paracetamol reduction and 82% COD removal by UV-C Fenton process are observed in a 120 min reaction time. By HPLC analysis, 100% removal of paracetamol is observed at the above optimum conditions for the Fenton process in 240 min and for the UV-C photo-Fenton process in 120 min. The methods are effective and they may be used in the paracetamol industry.

Sodium and chlorine concentrations in mixed saliva of healthy and cystic fibrosis children

Energy Technology Data Exchange (ETDEWEB)

Jimenez-Reyes, M. [Instituto Nacional de Investigaciones Nucleares, Mexico City (Mexico); Sanchez-Aguirre, F.J. [Instituto Mexicano del Seguro Social (Mexico). Dept. de Genetica

1996-03-01

Sodium and chlorine concentrations in mixed saliva were simultaneously measured by neutron activation analysis in nine normal children and in nine patients with cystic fibrosis. Sodium levels showed a significant difference (P < 0.01) between patients and controls. The concentration of chlorine was similar in both the control and the cystic fibrosis groups. (author).

Sodium and chlorine concentrations in mixed saliva of healthy and cystic fibrosis children

International Nuclear Information System (INIS)

Jimenez-Reyes, M.; Sanchez-Aguirre, F.J.

1996-01-01

Sodium and chlorine concentrations in mixed saliva were simultaneously measured by neutron activation analysis in nine normal children and in nine patients with cystic fibrosis. Sodium levels showed a significant difference (P < 0.01) between patients and controls. The concentration of chlorine was similar in both the control and the cystic fibrosis groups. (author)

DEVELOPMENT OF DOMESTIC INFUSION DRUGS BASED ON PARACETAMOL

Directory of Open Access Journals (Sweden)

Almakaeva L.G.

2016-06-01

Full Text Available The intravenous form of paracetamol compared with oral more reliably supports effective drug concentration in blood plasma that promotes a higher therapeutic effect. Recent studies have confirmed that the use of the intravenous form of paracetamol to deal with postoperative pain multimodal analgesia modes results in reducing the frequency and quantity of opioids administered , and, as a consequence, its associated side effects. The drug Paracetamol , infusion solution 10 mg / ml to 100 ml glass bottles is a drug - generic . His qualitative and quantitative composition is developed from the study of literature data about the drug - similar to " Perfalhan , 10 mg / ml solution for infusion in 100 mL " company Bristol - Myers Squibb, France and experimental work. The aim of our study is development and support of the national composition of the infusion of the drug on the basis of paracetamol, selection of excipients that provide stability of the active substances. Materials and methods. The object of the study was the substance of paracetamol manufactured by Zhejiang Kangle Pharmaceutical Co. , Ltd, China. During the work conducted qualitative and quantitative monitoring sample preparation for indicators of stability: pH content of the active ingredient , transparency, color, impurities , contamination by the methods described in the SFU [and nor- ral documentation to the drug . One potential factor of instability is the effect of paracetamol oxygen, due to the presence in the molecule of paracetamol and -NH possibility of oxidation. Results and Discussion. Paracetamol is derived atsetamina . Substance acetylation are p - aminophenol with acetic anhydride . Saturated aqueous solution has a pH of paracetamol - ment about 6 . Paracetamol is a crystalline white powder , sparingly soluble in water, soluble in 96% alcohol, very slightly soluble in metilenhloride . . Active substance enters in comparison drug in the concentration of 10 mg/ml. Stable

Randomised controlled trial comparing oral and intravenous paracetamol (acetaminophen) plasma levels when given as preoperative analgesia.

Science.gov (United States)

van der Westhuizen, J; Kuo, P Y; Reed, P W; Holder, K

2011-03-01

Gastric absorption of oral paracetamol (acetaminophen) may be unreliable perioperatively in the starved and stressed patient. We compared plasma concentrations of parenteral paracetamol given preoperatively and oral paracetamol when given as premedication. Patients scheduled for elective ear; nose and throat surgery or orthopaedic surgery were randomised to receive either oral or intravenous paracetamol as preoperative medication. The oral dose was given 30 minutes before induction of anaesthesia and the intravenous dose given pre-induction. All patients were given a standardised anaesthetic by the same specialist anaesthetist who took blood for paracetamol concentrations 30 minutes after the first dose and then at 30 minute intervals for 240 minutes. Therapeutic concentrations of paracetamol were reached in 96% of patients who had received the drug parenterally, and 67% of patients who had received it orally. Maximum median plasma concentrations were 19 mg.l(-1) (interquartile range 15 to 23 mg.l(-1)) and 13 mg.l(-1) (interquartile range 0 to 18 mg.l(-1)) for the intravenous and oral group respectively. The difference between intravenous and oral groups was less marked after 150 minutes but the intravenous preparation gave higher plasma concentrations throughout the study period. It can be concluded that paracetamol gives more reliable therapeutic plasma concentrations when given intravenously.

Paracetamol suppositories: a comparative study.

OpenAIRE

Cullen, S; Kenny, D; Ward, O C; Sabra, K

1989-01-01

Paracetamol suppositories in two different bases were given to children who had fever after operations. Plasma concentrations and the effect on temperature were compared. There was a significant correlation between peak plasma concentrations and maximum drop in temperature. A lipophilic base produced better results than a hydrophilic base.

The effect of sex and time of day on testosterone concentrations in equine saliva and serum

DEFF Research Database (Denmark)

Andersen, Rikke Munk; Jensen, R.B.; Palme, R.

2016-01-01

In terms of exercise, testosterone is important for the growth and maintenance of skeletal muscle mass. Sampling saliva could be a non-invasive alternative to blood sampling for the quantification of testosterone levels in horses. The objective of this study was to compare testosterone concentrat......In terms of exercise, testosterone is important for the growth and maintenance of skeletal muscle mass. Sampling saliva could be a non-invasive alternative to blood sampling for the quantification of testosterone levels in horses. The objective of this study was to compare testosterone......:00-08:00), at midday (11:00-13:00) and in the evening (17:00-19:00). The results demonstrated a weak correlation between saliva and serum testosterone concentrations (rs=0.25, P=0.04). Stallions had higher serum testosterone concentrations than mares and geldings (Peffect of sex...

Relative bioavailability and plasma paracetamol profiles of Panadol suppositories in children.

Science.gov (United States)

Coulthard, K P; Nielson, H W; Schroder, M; Covino, A; Matthews, N T; Murray, R S; Van Der Walt, J H

1998-10-01

To determine the relative bioavailability and plasma paracetamol concentration profiles following administration of a proprietary formulation of paracetamol suppositories to postoperative children. Study A-eight children undergoing minor surgery had blood samples collected following the rectal administration of either a 250 mg or 500 mg paracetamol suppository on one day and an equivalent oral dose on the following day. A mean dose of 13 mg/kg gave a mean Cmax (Tmax) of 7.7 mg/L (1.6 h) and 4.9 mg/L (2.0 h) following oral and rectal administration, respectively. The mean relative rectal bioavailability was 78% (95% confidence interval of 55-101%). Study B-20 children undergoing tonsillectomy and/or adenoidectomy were randomly assigned to receive a postoperative dose of 500 mg of paracetamol either as 2 x 250 mg liquid filled or 1 x 500 mg hard wax Panadol suppository. A mean dose of 25 mg/kg produced mean maximum plasma paracetamol concentrations of 13.2 mg/L and 14.5 mg/L at 2.1 and 1.9 h for the hard and liquid filled suppository, respectively. The absorption rate constants and areas under the curves suggested no difference in the rate or extent of absorption between the two formulations. Absorption of paracetamol following rectal administration of Panadol suppositories to postoperative children is slower and reduced as compared to oral therapy. The hard wax and liquid filled products have similar absorption characteristics. The usually quoted antipyretic therapeutic range for paracetamol is 10-20 mg/L, although 5 mg/L may be effective. A single rectal dose of 25 mg/kg will obtain this lower concentration within 1 h of administration and maintain it for up to 6 h. When given in an appropriate dose for analgesia, maximum plasma paracetamol concentrations would be available in the immediate postoperative period if the rectal dose was given 2 h before the planned end of the procedure.

Paracetamol suppositories: a comparative study.

Science.gov (United States)

Cullen, S; Kenny, D; Ward, O C; Sabra, K

1989-01-01

Paracetamol suppositories in two different bases were given to children who had fever after operations. Plasma concentrations and the effect on temperature were compared. There was a significant correlation between peak plasma concentrations and maximum drop in temperature. A lipophilic base produced better results than a hydrophilic base. PMID:2817936

Outcomes from massive paracetamol overdose: a retrospective observational study.

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Marks, Daniel J B; Dargan, Paul I; Archer, John R H; Davies, Charlotte L; Dines, Alison M; Wood, David M; Greene, Shaun L

2017-06-01

This article is commented on by Bateman DN and Dear JW. Should we treat very large paracetamol overdose differently? Br J Clin Pharmacol 2017; 83: 1163-5. https://doi.org/10.1111/bcp.13279 AIMS: Treatment of paracetamol (acetaminophen) overdose with acetylcysteine is standardized, with dose determined only by patient weight. The validity of this approach for massive overdoses has been questioned. We systematically compared outcomes in massive and non-massive overdoses, to guide whether alternative treatment strategies should be considered, and whether the ratio between measured timed paracetamol concentrations (APAP pl ) and treatment nomogram thresholds at those time points (APAP t ) provides a useful assessment tool. This is a retrospective observational study of all patients (n = 545) between 2005 and 2013 admitted to a tertiary care toxicology service with acute non-staggered paracetamol overdose. Massive overdoses were defined as extrapolated 4-h plasma paracetamol concentrations >250 mg l -1 , or reported ingestions ≥30 g. Outcomes (liver injury, coagulopathy and kidney injury) were assessed in relation to reported dose and APAP pl :APAP t ratio (based on a treatment line through 100 mg l -1 at 4 h), and time to acetylcysteine. Ingestions of ≥30 g paracetamol correlated with higher peak serum aminotransferase (r = 0.212, P paracetamol overdose are at higher risk of organ injury, even when acetylcysteine is administered early. Enhanced therapeutic strategies should be considered in those who have an APAP pl :APAP t  ≥ 3. Novel biomarkers of incipient liver injury and abbreviated acetylcysteine regimens require validation in this patient cohort. © 2016 The British Pharmacological Society.

[Cotinine concentration in the saliva in relation to oral hygiene procedures].

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Bachanek, Teresa; Nakonieczna-Rudnicka, Marta; Piekarczyk, Wanda

2014-01-01

Cotinine is a biomarker of the exposure to the tobacco smoke, nicotine metabolite with half-life in the saliva which is 17 hours. Assessment of cotinine concentration enables among others verification of the questionnaire data as well as evaluation of both smokers and non-smokers exposure to the tobacco smoke. Practicing proper oral hygiene procedures is an essential factor of the prophylaxis of dental caries and periodontal diseases which influence general health state. The removal of dental calculus is achieved by proper teeth brushing and the use of additional oral aids. The aim of the study was evaluation of cotinine concentration in non-stimulated saliva in order to verify questionnaire data (smoker/non-smoker) and analysis of practicing oral hygiene procedures in relation to the status of cigarette smoking. Questionnaire and biochemical studies were conducted in the group of 116 people aged 20-54. In questionnaire survey 53 people (45.69%) confirmed cigarette smoking, 63 (54.31%) declared they had never smoked and never tried to smoke. Non-stimulated saliva was collected between 9(30) and 11(30), 1,5-2 hours after meal. Cotinine concentration was assayed with the use of Cotinine ELISA (Calbiotech, USA). Obtained study results were submitted to statistic analysis with the use of Chi2. Statistically essential test values were those with psmokers and 4.76% non-smokers, brushing teeth at least twice a day was reported subsequently by 73.08% and 95.24% participants. Non-smokers in comparison with smokers considerably more frequently brushed their teeth, at least twice a day (XZ=11.11, pSmokers used a toothbrush with medium hardness bristle (X2=6.05, pSmokers more fre. quently brushed their teeth improperly (X2=1 3.41, pSmokers in comparison with non-smokers did not practice proper oral hygiene which is an essential risk factor of the oral health. It is crucial for dental surgeons to conduct oral hygiene instructions in smokers as well as realization of health

Influence of fruit drinks with or without lactobacillus Lp299v on the gastrointestinal uptake of paracetamol in man

DEFF Research Database (Denmark)

Akerman, Ulrika; Edvinsson, Lars

2009-01-01

subjects consuming 200 ml of water, Rose hip drink or Proviva together with 1.5 gram of paracetamol. FINDINGS: The concentration of paracetamol in plasma increased rapidly when the paracetamol-containing tablets were consumed together with water and after 30 minutes a median level of 90 mumol/l was reached...... concentration and in time to maximal paracetamol concentration. The median maximal paracetamol concentration was 147 mumol/l for water, which is significantly higher than the median for rosehip drink with Lp299v,113.5 mumol/l, and than the median for rosehip-drink without Lp299v, 106.5 mumol/l (p = 0.002, and p...

Flow rate, pH and calcium concentration of saliva of children and adolescents with type 1 diabetes mellitus

Directory of Open Access Journals (Sweden)

A.R. Moreira

2009-08-01

Full Text Available Alterations in salivary parameters may increase the caries risk in diabetic children, but, contradictory data on this issue have been reported. The aims of this study were to compare salivary parameters (flow rate, pH and calcium concentration between healthy and type 1 diabetes mellitus (T1DM individuals. The sample consisted of 7- to 18-year-old individuals divided into two groups: 30 subjects with T1DM (group A and 30 healthy control subjects (group B. Fasting glucose levels were determined. Unstimulated and stimulated saliva was collected. The pH of unstimulated saliva was measured with paper strips and an electrode. Calcium concentrations in stimulated saliva were determined with a selective electrode. Group A individuals had inadequate blood glucose control (HbA1C >9%, with means ± SD unstimulated salivary flow rate of 0.15 ± 0.1 mL/min compared to 0.36 ± 0.2 mL/min for group B (P < 0.01. Stimulated salivary flow rate was similar by both groups and above 2.0 mL/min. Saliva pH was 6.0 ± 0.8 for group A and significantly different from 7.0 ± 0.6 for group B (P < 0.01. Salivary calcium was 14.7 ± 8.1 mg/L for group A and significantly higher than 9.9 ± 6.4 mg/L for group B (P < 0.01. Except for elevated calcium concentrations in saliva, salivary parameters favoring caries such as low saliva pH and unstimulated salivary flow rate were observed in T1DM individuals.

[A patient who refused treatment after self-poisoning with paracetamol

NARCIS (Netherlands)

Kramers, C.; Jansman, F.G.A.; Droogleever Fortuyn, H.A.

2006-01-01

Two patients, a 20-year-old man and a 33-year-old woman, were admitted with paracetamol poisoning. Both patients refused treatment initially but eventually complied. The man had a paracetamol concentration of 47.5 mg/l 2.5-5.0 h after ingestion, so antidote treatment was not considered necessary.

Usefulness of saliva for measurement of 3,4-methylenedioxymethamphetamine and its metabolites: correlation with plasma drug concentrations and effect of salivary pH.

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Navarro, M; Pichini, S; Farré, M; Ortuño, J; Roset, P N; Segura, J; de la Torre, R

2001-10-01

Saliva is an alternative biologic matrix for drugs-of-abuse testing that offers the advantages of noninvasive, rapid, and easy sampling. We studied the excretion profile of 3,4-methylenedioxymethamphetamine (MDMA) and its metabolites in both saliva and plasma, as well the effect of the drug on salivary pH. Saliva and plasma samples were obtained from eight healthy MDMA consumers after ingestion of a single 100-mg dose of the drug. Concentrations of MDMA and its main metabolites, 3,4-methylenedioxyamphetamine (MDA) and 4-hydroxy-3-methoxymethamphetamine (HMMA), in saliva and plasma were measured by gas chromatography-mass spectrometry. Apparent pharmacokinetic parameters for MDMA in saliva were estimated, and the saliva-to-plasma ratio at each time interval was calculated and correlated with salivary pH. MDMA, MDA, and HMMA were detected in saliva. Salivary concentrations of MDMA were 1728.9-6510.6 microg/L and peaked at 1.5 h after drug intake. This was followed by a progressive decrease, with a mean concentration of 126.2 microg/L at 24 h. The saliva-to-plasma ratio was 32.3-1.2, with a peak of 18.1 at 1.5 h after drug administration. Salivary pH seemed to be affected by MDMA administration; pH values decreased by 0.6 units (mean pH values of 6.9 and 6.8 at 1.5 and 4 h after drug administration vs predose pH of 7.4). Measurement of MDMA in saliva is a valuable alternative to determination of plasma drug concentrations in both clinical and toxicologic studies. On-site testing is also facilitated by noninvasive and rapid collection of salivary specimens.

Accuracy of the paracetamol-aminotransferase product to predict hepatotoxicity in paracetamol overdose treated with a 2-bag acetylcysteine regimen.

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Wong, Anselm; Sivilotti, Marco L A; Gunja, Naren; McNulty, Richard; Graudins, Andis

2018-03-01

Paracetamol concentration is a highly accurate risk predictor for hepatotoxicity following overdose with known time of ingestion. However, the paracetamol-aminotransferase multiplication product can be used as a risk predictor independent of timing or ingestion type. Validated in patients treated with the traditional, "three-bag" intravenous acetylcysteine regimen, we evaluated the accuracy of the multiplication product in paracetamol overdose treated with a two-bag acetylcysteine regimen. We examined consecutive patients treated with the two-bag regimen from five emergency departments over a two-year period. We assessed the predictive accuracy of initial multiplication product for the primary outcome of hepatotoxicity (peak alanine aminotransferase ≥1000IU/L), as well as for acute liver injury (ALI), defined peak alanine aminotransferase ≥2× baseline and above 50IU/L). Of 447 paracetamol overdoses treated with the two-bag acetylcysteine regimen, 32 (7%) developed hepatotoxicity and 73 (16%) ALI. The pre-specified cut-off points of 1500 mg/L × IU/L (sensitivity 100% [95% CI 82%, 100%], specificity 62% [56%, 67%]) and 10,000 mg/L × IU/L (sensitivity 70% [47%, 87%], specificity of 97% [95%, 99%]) were highly accurate for predicting hepatotoxicity. There were few cases of hepatotoxicity irrespective of the product when acetylcysteine was administered within eight hours of overdose, when the product was largely determined by a high paracetamol concentration but normal aminotransferase. The multiplication product accurately predicts hepatotoxicity when using a two-bag acetylcysteine regimen, especially in patients treated more than eight hours post-overdose. Further studies are needed to assess the product as a method to adjust for exposure severity when testing efficacy of modified acetylcysteine regimens.

Paracetamol (acetaminophen) attenuates in vitro mast cell and peripheral blood mononucleocyte cell histamine release induced by N-acetylcysteine.

Science.gov (United States)

Coulson, James; Thompson, John Paul

2010-02-01

The treatment of acute paracetamol (acetaminophen) poisoning with N-acetylcysteine (NAC) is frequently complicated by an anaphylactoid reaction to the antidote. The mechanism that underlies this reaction is unclear. We used the human mast cell line 1 (HMC-1) and human peripheral blood mononucleocytes (PBMCs) to investigate the effects of NAC and paracetamol on histamine secretion in vitro. HMC-1 and human PBMCs were incubated in the presence of increasing concentrations of NAC +/- paracetamol. Cell viability was determined by the Trypan Blue Assay, and histamine secretion was measured by ELISA. NAC was toxic to HMC-1 cells at 100 mg/mL and to PBMCs at 67 mg/mL. NAC increased HMC-1 and PBMC histamine secretion at concentrations of NAC from 20 to 50 mg/mL and 2.5 to 100 mg/mL, respectively. NAC-induced histamine secretion by both cell types was reduced by co-incubation with 2.5 mg/mL of paracetamol. Paracetamol (acetaminophen) is capable of modifying histamine secretion in vitro. This may explain the clinical observation of a lower incidence of adverse reactions to NAC in vivo when higher concentrations of paracetamol are present than when paracetamol concentrations are low. Paracetamol (acetaminophen) attenuates in vitro mast cell and PBMC cell histamine release induced by NAC.

Paracetamol poisoning and hepatotoxicity in Chinese--the Prince of Wales Hospital (Hong Kong) experience.

Science.gov (United States)

Chan, T Y; Chan, A Y; Critchley, J A

1993-08-01

From 1989 to 1991, 104 Chinese patients were admitted to the Prince of Wales Hospital with paracetamol poisoning. Only 11 subjects had a plasma paracetamol concentration above the published treatment line. Intravenous N-acetylcysteine (NAC) was completely effective when given within 8 hours (3 patients), while late treatment with NAC at 16 and 26 hours after overdose (2 patients) was ineffective in preventing liver damage as evidenced by elevations in plasma alanine transaminase concentrations. Of the 6 patients receiving NAC between 10 to 15 hours, two had liver damage. Two other subjects who presented late or in whom a plasma paracetamol concentration was not measured also developed liver damage. Fortunately, none of these 6 subjects developed hepatic encephalopathy. We recommend that a standard protocol be readily available for junior hospital staff to use when treating patients with paracetamol overdosage.

[Corrosion resistance of casted titanium by compound treatments in the artificial saliva with different fluoride concentrations].

Science.gov (United States)

Wang, Xian-li; Guo, Tian-wen

2012-09-01

To study the corrosion resistance of casted titanium by plasma nitriding and TiN-coated compound treatments in the artificial saliva with different fluoride concentrations and to investigate whether compound treatments can increase the corrosion resistance of casted titanium. Potentiodynamic polarization technique was used to depict polarization curve and to measured the current density of corrosion (Icorr) and the electric potential of corrosion (Ecorr) of casted titanium (Group A) and casted titanium by compound treatments (Group B) in the artificial saliva with different fluoride concentrations. After electrochemical experiment, the microstructure was observed by scanning electron microscope (SEM). The Icorrs of Group A and B in the artificial saliva of different fluoride concentrations were (1530.23 ± 340.12), (2290.36 ± 320.10), (4130.52 ± 230.17) nA and (2.62 ± 0.64), (7.37 ± 3.59), (10.76 ± 6.05) nA, respectively. The Ecorrs were (-0.93 ± 0.10), (-0.89 ± 0.21), (-0.57 ± 0.09) V and (-0.21 ± 0.04), (-0.17 ± 0.03), (-0.22 ± 0.03) V, respectively.The Icorrs of Group B were significantly lower (P compound treatments can significantly increase the corrosion resistance of casted titanium.

Can paracetamol (acetaminophen) be administered to patients with liver impairment?

Science.gov (United States)

Hayward, Kelly L; Powell, Elizabeth E; Irvine, Katharine M; Martin, Jennifer H

2016-02-01

Although 60 years have passed since it became widely available on the therapeutic market, paracetamol dosage in patients with liver disease remains a controversial subject. Fulminant hepatic failure has been a well documented consequence of paracetamol overdose since its introduction, while short and long term use have both been associated with elevation of liver transaminases, a surrogate marker for acute liver injury. From these reports it has been assumed that paracetamol use should be restricted or the dosage reduced in patients with chronic liver disease. We review the factors that have been purported to increase risk of hepatocellular injury from paracetamol and the pharmacokinetic alterations in different pathologies of chronic liver disease which may affect this risk. We postulate that inadvertent under-dosing may result in concentrations too low to enable efficacy. Specific research to improve the evidence base for prescribing paracetamol in patients with different aetiologies of chronic liver disease is needed. © 2015 The British Pharmacological Society.

Dynamic changes in saliva after acute mental stress

Science.gov (United States)

Naumova, Ella A.; Sandulescu, Tudor; Bochnig, Clemens; Khatib, Philipp Al; Lee, Wing-Kee; Zimmer, Stefan; Arnold, Wolfgang H.

2014-01-01

Stress-related variations of fluoride concentration in supernatant saliva and salivary sediment, salivary cortisol, total protein and pH after acute mental stress were assessed. The hypothesis was that stress reactions have no influence on these parameters. Thirty-four male students were distributed into two groups: first received the stress exposure followed by the same protocol two weeks later but without stress exposure, second underwent the protocol without stress exposure followed by the stress exposure two weeks later. The stressor was a public speech followed by tooth brushing. Saliva was collected before, immediately after stress induction and immediately, at 10, 30 and 120 min. after tooth brushing. Cortisol concentrations, total protein, intraoral pH, and fluoride content in saliva were measured. The data were analyzed statistically. Salivary sediment was ca 4.33% by weight of whole unstimulated saliva. Fluoride bioavailability was higher in salivary sediment than in supernatant saliva. The weight and fluoride concentration was not altered during 2 hours after stress exposure. After a public speech, the salivary cortisol concentration significantly increased after 20 minutes compared to the baseline. The salivary protein concentration and pH also increased. Public speaking influences protein concentration and salivary pH but does not alter the fluoride concentration of saliva. PMID:24811301

Pharmacokinetics of Oral and Intravenous Paracetamol (Acetaminophen) When Co-Administered with Intravenous Morphine in Healthy Adult Subjects.

Science.gov (United States)

Raffa, Robert B; Pawasauskas, Jayne; Pergolizzi, Joseph V; Lu, Luke; Chen, Yin; Wu, Sutan; Jarrett, Brant; Fain, Randi; Hill, Lawrence; Devarakonda, Krishna

2018-03-01

Several features favor paracetamol (acetaminophen) administration by the intravenous rather than the oral route in the postoperative setting. This study compared the pharmacokinetics and bioavailability of oral and intravenous paracetamol when given with or without an opioid, morphine. In this randomized, single-blind, parallel, repeat-dose study in healthy adults, subjects received four repeat doses of oral or intravenous 1000 mg paracetamol at 6-h intervals, and morphine infusions (0.125 mg/kg) at the 2nd and 3rd intervals. Comparisons of plasma pharmacokinetic profiles were conducted before, during, and after opioid co-administrations. Twenty-two subjects were included in the pharmacokinetic analysis. Observed paracetamol peak concentration (C max ) and area under the plasma concentration-time curve over the dosing interval (AUC 0-6 ) were reduced when oral paracetamol was co-administered with morphine (reduced from 11.6 to 7.25 µg/mL and from 31.00 to 25.51 µg·h/mL, respectively), followed by an abruptly increased C max and AUC 0-6 upon discontinuation of morphine (to 13.5 µg/mL and 52.38 µg·h/mL, respectively). There was also a significantly prolonged mean time to peak plasma concentration (T max ) after the 4th dose of oral paracetamol (2.84 h) compared to the 1st dose (1.48 h). However, pharmacokinetic parameters of paracetamol were not impacted when intravenous paracetamol was co-administered with morphine. Morphine co-administration significantly impacted the pharmacokinetics of oral but not intravenous paracetamol. The abrupt release of accumulated paracetamol at the end of morphine-mediated gastrointestinal inhibition following oral but not intravenous administration of paracetamol suggests that intravenous paracetamol provides a better option for the management of postoperative pain. CLINICALTRIALS. NCT02848729.

Bioequivalence and Safety of Twice-Daily Sustained-Release Paracetamol (Acetaminophen) Compared With 3- and 4-Times-Daily Paracetamol: A Repeat-Dose, Crossover Pharmacokinetic Study in Healthy Volunteers.

Science.gov (United States)

Liu, Dongzhou J; Collaku, Agron

2018-01-01

Twice-daily sustained-release (SR) paracetamol (acetaminophen) offers convenient administration to chronic users. This study investigated at steady state (during the last 24 hours of a 3-day dosing period) the pharmacokinetics, bioequivalence, and safety of twice-daily SR paracetamol compared with extended-release (ER) and immediate-release (IR) paracetamol. In this open-label, randomized, multidose, 3-way crossover study, 28 healthy subjects received paracetamol SR (2 × 1000 mg twice daily), ER (2 × 665 mg 3 times daily), and IR (2 × 500 mg 4 times daily). At steady state, twice-daily SR paracetamol was bioequivalent to ER and IR paracetamol. The 90% confidence intervals for the ratios of geometric means were within the acceptance interval for SR/ER paracetamol (AUC 0-t , 0.973-1.033; AUC 0-24 , 0.974-1.034; AUC 0-∞ , 0.948-1.011; C max , 1.082-1.212; C av , 1.011-1.106) and SR/IR paracetamol (AUC 0-t , 0.969-1.029; AUC 0-24 , 0.968-1.027; AUC 0-∞ , 0.963-1.026; C max , 0.902-1.010; C av , 1.004-1.098). Given twice daily, the SR formulation demonstrated SR properties as expected. Mean time at or above a 4 μg/mL plasma concentration of paracetamol from 2 daily doses of the SR formulation was significantly longer than that from 4 daily doses of IR paracetamol. SR formulation also had a greater T max , a longer half-life, and lower C min compared with ER and IR paracetamol. All formulations were well tolerated. © 2017, The American College of Clinical Pharmacology.

Factors That Influence the Extensional Rheological Property of Saliva.

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Amrita Vijay

Full Text Available The spinnbarkeit of saliva reflects the ability of saliva to adhere to surfaces within the mouth, thereby serving as a protective role and aiding in lubrication. Therefore, alterations in the extensional rheology of saliva may result in the loss in adhesiveness or the ability to bind onto surfaces. Mucin glycoproteins and their structures are known to be important factors for the extensional rheological properties of saliva. The conformation of mucin depends on factors such as pH and ionic strength. Chewing is one of the main stimuli for salivary secretion but creates significant sheer stress on the salivary film which could influence mouthfeel perceptions. The current study investigates the possible factors which affect the extensional rheological properties of saliva by comparing submandibular/sublingual saliva with different oral stimuli within the same group of subjects. Unstimulated and stimulated saliva (chew, smell and taste salivas were collected primarily from submandibular/sublingual glands. The saliva samples were measured for Spinnbarkeit followed by the measuring mucin, total protein, total calcium and bicarbonate concentrations. The results indicated correlations between rheological properties and mucin/ion concentrations. However, chewing stimulated submandibular/sublingual saliva is shown to have significantly lower Spinnbarkeit, but factors such as mucin, protein and calcium concentrations did not account for this variation. Analysis of the concentration of bicarbonate and pH appears to suggest that it has a prominent effect on extensional rheology of saliva.

Determinants of hepatotoxicity after repeated supratherapeutic paracetamol ingestion: systematic review of reported cases.

Science.gov (United States)

Acheampong, Paul; Thomas, Simon H L

2016-10-01

To evaluate the role of reported daily dose, age and other risk factors, and to assess the value of quantifying serum transaminase activity and paracetamol (acetaminophen) concentration at initial assessment for identifying patients at risk of hepatotoxicity following repeated supratherapeutic paracetamol ingestion (RSPI). Systematic literature review with collation and analysis of individual-level data from reported cases of RSPI associated with liver damage. In 199 cases meeting the selection criteria, severe liver damage (ALT/AST ≥1000 IU l(-1) , liver failure or death) was reported in 186 (93%) cases including 77/78 (99%) children aged ≤6 years. Liver failure occurred in 127 (64%) cases; of these 49 (39%) died. Maximum ingested daily paracetamol doses were above UK recommendations in 143 (72%) patients. US-Australasian thresholds for repeated supratherapeutic ingestions requiring intervention were not met in 71 (36%) cases; of these 35 (49%) developed liver failure and 10 (14%) died. No cases developing liver damage had paracetamol concentration Paracetamol concentrations <20 mg l(-1) with normal serum ALT/AST activity on initial assessment suggests a low risk of subsequent liver damage. These findings are, however, limited by low patient numbers, publication bias and the accuracy of the histories in reported cases. © 2016 The British Pharmacological Society.

Concentration of total protein and degree of acidity (pH of saliva when fasting and after breakfasting

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Gemella Nur Illahi

2016-04-01

Full Text Available Background: While fasting, the mouth does not work to eat and drink so that the salivary glands become less active so saliva production decreased and there was a change in eating timewhich is relation to the mastication process that impact on changes in the degree of acidity (pH Objectives: To determine the concentration of total protein and the degree of acidity (pH of saliva when fasting and after breakfasting. Materials and Methods: The study was observational analytic design with longitudinal (follow up study conducted in the Hj. Halima Dg. Sikati Dental Hospital inKandea in July 2015, the sampling method was purposive sampling. Population was 35 clinical students at the Department of Dental Public Health, Faculty of Dentistry Hasanuddin University with a total sample of 16 students who fit the criteria of the study subjects. To calculate the total protein of saliva concentration using Kyltecautoanalyzerand pH meter to measure the acidity of saliva. Data was analyzed was using SPSS version 17.0 (paired t-test, p <0.05. Results: The mean of total protein (% while fasting by 0135% ± 0.026 and the mean total protein (% after breakfasting at 0.179% ± 0.035, while the average degree of acidity (pH during fasting at 7.26 ± 0:24 and the average degree of acidity (pH after breakfasting at 7.66 ± 0.23 with p-value (0.000. Conclusions: An increase in the total protein concentration and acidity (pH after breakfasting.

Aniline Is Rapidly Converted Into Paracetamol Impairing Male Reproductive Development.

Science.gov (United States)

Holm, Jacob Bak; Chalmey, Clementine; Modick, Hendrik; Jensen, Lars Skovgaard; Dierkes, Georg; Weiss, Tobias; Jensen, Benjamin Anderschou Holbech; Nørregård, Mette Marie; Borkowski, Kamil; Styrishave, Bjarne; Martin Koch, Holger; Mazaud-Guittot, Severine; Jegou, Bernard; Kristiansen, Karsten; Kristensen, David Møbjerg

2015-11-01

Industrial use of aniline is increasing worldwide with production estimated to surpass 5.6 million metric tons in 2016. Exposure to aniline occurs via air, diet, and water augmenting the risk of exposing a large number of individuals. Early observations suggest that aniline is metabolized to paracetamol/acetaminophen, likely explaining the omnipresence of low concentrations of paracetamol in European populations. This is of concern as recent studies implicate paracetamol as a disrupter of reproduction. Here, we show through steroidogenic profiling that exposure to aniline led to increased levels of the Δ4 steroids, suggesting that the activity of CYP21 was decreased. By contrast, paracetamol decreased levels of androgens likely through inhibition of CYP17A1 activity. We confirm that aniline in vivo is rapidly converted to paracetamol by the liver. Intrauterine exposure to aniline and paracetamol in environmental and pharmaceutical relevant doses resulted in shortening of the anogenital distance in mice, a sensitive marker of fetal androgen levels that in humans is associated with reproductive malformations and later life reproductive disorders. In conclusion, our results provide evidence for a scenario where aniline, through its conversion into antiandrogenic paracetamol, impairs male reproductive development. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Interventions for paracetamol (acetaminophen) overdoses

DEFF Research Database (Denmark)

Brok, J; Buckley, N; Gluud, C

2002-01-01

Self-poisoning with paracetamol (acetaminophen) is a common cause of hepatotoxicity in the Western World. Interventions for paracetamol poisoning encompass inhibition of absorption, removal from the vascular system, antidotes, and liver transplantation.......Self-poisoning with paracetamol (acetaminophen) is a common cause of hepatotoxicity in the Western World. Interventions for paracetamol poisoning encompass inhibition of absorption, removal from the vascular system, antidotes, and liver transplantation....

A simple assay of paracetamol based on dried blood spot suitable ...

African Journals Online (AJOL)

Dried blood spots in Guthrie cards are a reliable means of blood sampling suitable for pharmacoki-netic analysis in children. The aim of this study was to develop a simple and reliable bioanalytical method to measure the concentration of paracetamol in dried blood spots. Paracetamol was ex-tracted from dry blood spots by ...

Combined paracetamol and amitriptyline adsorption to activated charcoal

DEFF Research Database (Denmark)

Hoegberg, Lotte Christine Groth; Groenlykke, Thor Buch; Abildtrup, Ulla

2010-01-01

Objectives. High-gram drug doses seen in multiple-drug poisonings might be close to the adsorption capacity of activated charcoal (AC). The aim was to determine the maximum adsorption capacities (Q(m)) of amitriptyline and paracetamol, separately and in combination, to AC. Methods. ACs (Carbomix......® and Norit Ready-To-Use) were tested in vitro. At pH 1.2 and pH 7.2, 0.250 g AC and paracetamol and/or amitriptyline were mixed and incubated. The AC: drug ratios were 10:1, 5:1, 3:1, 2:1, and 1:1. The mixed-drug adsorption vials contained the same AC: paracetamol ratios, but amitriptyline was added as fixed...... dose (0.080 g) to all samples. Drug concentrations in the liquid phase were analyzed using high-performance liquid chromatography (HPLC)/UV-detection. Results. Q(m), amitriptyline, were 0.49 g/g Carbomix® and 0.70 g/g Norit Ready-To-Use, and Q(m), paracetamol, were 0.63 g/g Carbomix® and 0.72 g/g Norit...

A review of the evidence concerning hepatic glutathione depletion and susceptibility to hepatotoxicity after paracetamol overdose

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Kalsi SS

2011-12-01

Full Text Available Sarbjeet S Kalsi1,2, Paul I Dargan2–4, W Stephen Waring5, David M Wood2–41Emergency Department, Guy’s and St Thomas’ NHS Foundation Trust, London, UK; 2Clinical Toxicology, Guy’s and St Thomas’ NHS Foundation Trust, London, UK; 3King’s Health Partners, London, UK; 4King’s College London, London, UK; 5York Teaching Hospital NHS Foundation Trust, York, UKAbstract: Paracetamol (acetaminophen poisoning is common throughout the world. The management of nonstaggered (acute paracetamol overdose is based on the plasma paracetamol concentration plotted on a treatment nomogram. In the UK there are two treatment lines on this nomogram, with the lower treatment line used for individuals felt to be at ‘high risk’ of paracetamol-related hepatotoxicity either as a result of induction of cytochrome P450 isoenzymes or reduction of intrahepatic glutathione. In this article we review the risk factors that, in current guidelines, are felt to increase risk due to a reduction in intrahepatic glutathione concentrations. Based on our review of the published literature, we feel that cystic fibrosis, acute viral illness, malnutrition, and eating disorders such as anorexia nervosa are likely to be associated with reduction in intrahepatic glutathione concentrations, and that this risk is likely to be related to malnutrition secondary to the disease. Chronic hepatitis C infection is also associated with reduced glutathione concentrations, although this appears to be independent of any associated malnutrition. Ageing and acute fasting are not associated with an increased risk of paracetamol-related hepatotoxicity due to reductions in glutathione concentrations. Finally, the evidence for HIV infection is inconclusive, particularly as the majority of studies were conducted in the pre-anti-viral treatment (HAART era; however it is likely that patients with symptomatic HIV/AIDS have reduced glutathione concentrations due to associated malnutrition. Although

Flow rate, pH and calcium concentration of saliva of children and adolescents with type 1 diabetes mellitus.

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Moreira, A R; Passos, I A; Sampaio, F C; Soares, M S M; Oliveira, R J

2009-08-01

Alterations in salivary parameters may increase the caries risk in diabetic children, but, contradictory data on this issue have been reported. The aims of this study were to compare salivary parameters (flow rate, pH and calcium concentration) between healthy and type 1 diabetes mellitus (T1DM) individuals. The sample consisted of 7- to 18-year-old individuals divided into two groups: 30 subjects with T1DM (group A) and 30 healthy control subjects (group B). Fasting glucose levels were determined. Unstimulated and stimulated saliva was collected. The pH of unstimulated saliva was measured with paper strips and an electrode. Calcium concentrations in stimulated saliva were determined with a selective electrode. Group A individuals had inadequate blood glucose control (HbA(1C) >9%), with means +/- SD unstimulated salivary flow rate of 0.15 +/- 0.1 mL/min compared to 0.36 +/- 0.2 mL/min for group B (P salivary flow rate was similar by both groups and above 2.0 mL/min. Saliva pH was 6.0 +/- 0.8 for group A and significantly different from 7.0 +/- 0.6 for group B (P Salivary calcium was 14.7 +/- 8.1 mg/L for group A and significantly higher than 9.9 +/- 6.4 mg/L for group B (P salivary parameters favoring caries such as low saliva pH and unstimulated salivary flow rate were observed in T1DM individuals.

Developmental changes rather than repeated administration drive paracetamol glucuronidation in neonates and infants.

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Krekels, Elke H J; van Ham, Saskia; Allegaert, Karel; de Hoon, Jan; Tibboel, Dick; Danhof, Meindert; Knibbe, Catherijne A J

2015-09-01

Based on recovered metabolite ratios in urine, it has been concluded that paracetamol glucuronidation may be up-regulated upon multiple dosing. This study investigates paracetamol clearance in neonates and infants after single and multiple dosing using a population modelling approach. A population pharmacokinetic model was developed in NONMEM VI, based on paracetamol plasma concentrations from 54 preterm and term neonates and infants, and on paracetamol, paracetamol-glucuronide and paracetamol-sulphate amounts in urine from 22 of these patients. Patients received either a single intravenous propacetamol dose or up to 12 repeated doses. Paracetamol and metabolite disposition was best described with one-compartment models. The formation clearance of paracetamol-sulphate was 1.46 mL/min/kg(1.4), which was about 5.5 times higher than the formation clearance of the glucuronide of 0.266 mL/min/kg. The renal excretion rate constants of both metabolites was estimated to be 11.4 times higher than the excretion rate constant of unchanged paracetamol, yielding values of 0.580 mL/min/kg. Developmental changes were best described by bodyweight in linear relationships on the distribution volumes, the formation of paracetamol-glucuronide and the unchanged excretion of paracetamol, and in an exponential relationship on the formation of paracetamol-sulphate. There was no evidence for up-regulation or other time-varying changes in any of the model parameters. Simulations with this model illustrate how paracetamol-glucuronide recovery in urine increases over time due to the slower formation of this metabolite and in the absence of up-regulation. Developmental changes, described by bodyweight-based functions, rather than up-regulation, explain developmental changes in paracetamol disposition in neonates and infants.

A New Sensor Based on Graphite Screen Printed Electrode Modified With Cu-Nanocomplex for Determination of Paracetamol

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Hadi Beitollai

2017-01-01

Full Text Available Paracetamol is a non-steroidal anti-inflammatory drug used as an antipyretic agent for the alternative to aspirin. Conversely, the overdoses of paracetamol can cause hepatic toxicity and kidney damage. Hence, the determination of paracetamol receives much more attention in biological samples and also in pharmaceutical formulations. Here, we report a rapid and sensitive detection of the paracetamol based on screen-printed modified electrode (SPE with Cu nanocomplex (Cu in pH=7.0. The paracetamol is not stable in strong acidic and strong alkaline media, and is hydrolyzed and hydroxylated. However, it is stable in intermediate pHs due to the dimerization of paracetamol. The kinetics of the paracetamol oxidation was briefly studied and documented in the schemes. In addition, the characterization of Cu nanocomplex was probed by Fourier transform infrared spectroscopy (FT-IR, X-ray diffraction (XRD, scanning electron microscopy (SEM, and energy dispersive X-ray spectroscopy (EDX. Moreover, the voltammetry determined the paracetamol with the linear concentration ranging from 10.0 to 1000.0 μM and the lower detection limit of 1.0 μM. This method was also successfully used to detect the concentration of paracetamol in pharmaceutical formulations and urine samples.

Influence of fruit drinks with or without lactobacillus Lp299v on the gastrointestinal uptake of paracetamol in man

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Edvinsson Lars

2009-03-01

Full Text Available Abstract Background Clinical observations have revealed that patients throw up undigested paracetamol tablets several hours following intake of rosehip drink with Lp299v (Proviva. The purpose of this study was to demonstrate if this translates into altered plasma levels of paracetamol in nineteen healthy subjects consuming 200 ml of water, Rose hip drink or Proviva together with 1.5 gram of paracetamol. Findings The concentration of paracetamol in plasma increased rapidly when the paracetamol-containing tablets were consumed together with water and after 30 minutes a median level of 90 μmol/l was reached (a 95% confidence interval of 57,161. The corresponding 30 minutes values of paracetamol levels in the presence of rosehip with or without Lp299v were 0 μmol/l (95% confidence intervals contain only zero for both rosehip treatments. There were significant differences in AUC, maximal paracetamol concentration and in time to maximal paracetamol concentration. The median maximal paracetamol concentration was 147 μmol/l for water, which is significantly higher than the median for rosehip drink with Lp299v,113.5 μmol/l, and than the median for rosehip-drink without Lp299v, 106.5 μmol/l (p = 0.002, and p = 0.003; there were no significant difference between rosehip drink with or without Lp299v (p > 0.3. Conclusion We have demonstrated an interaction between the uptake of paracetamol and the solvent in rosehip drink/Provia which mainly consists of long chain carbohydrates. This may in the clinic translate to the use of more drug than it is necessary.

Measurement of iron, magnesium and chromium concentrations in the saliva of the patients undergoing fixed orthodontic treatment

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Valiollah Arash

2012-09-01

Full Text Available Introduction: Stainless steel alloy used in orthodontics has elements such as iron - magnesium and chromium , which may be released due to corrosion in the mouth . The aim of this study was to evaluate the changes of these elements in the saliva of patients undergoing fixed orthodontic treatment. Methods: In a clinical study with simple non- random sampling , 1ml saliva of 11 patients (7 females and 4 males who needed fixed orthodontic treatment and had no restorations or crowns were collected. During the fixed orthodontic treatment at successive times ( a day, a week, a month , two months and six months , 1 ml of saliva was collected and evaluated for the amount of iron ( spectrophotometry, chromium ( atomic absorption, and magnesium ( spectrophotometry . Bracket , band and wire used in all patients were stainless steel alloy and were manufactured by Dentaurum Company. After sample collection , the data analysis was performed with " Azeri- 5" and "10SPSS" software and repeated measures test. Results: The mean concentration of iron 66.326±0.541, chromium 0.483±0.324 and magnesium 0.552±293 decreased during the study but these results were not statistical y significant (p>0.05. Conclusions: Iron , chromium and magnesium concentration do not exceed the standard limits in saliva during orthodontic treatment.

Electrocatalytic Study of Paracetamol at a Single-Walled Carbon Nanotube/Nickel Nanocomposite Modified Glassy Carbon Electrode

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Koh Sing Ngai

2015-01-01

Full Text Available A rapid, simple, and sensitive method for the electrochemical determination of paracetamol was developed. A single-walled carbon nanotube/nickel (SWCNT/Ni nanocomposite was prepared and immobilized on a glassy carbon electrode (GCE surface via mechanical attachment. This paper reports the voltammetry study on the effect of paracetamol concentration, scan rate, pH, and temperature at a SWCNT/Ni-modified electrode in the determination of paracetamol. The characterization of the SWCNT/Ni/GCE was performed by cyclic voltammetry. Variable pressure scanning electron microscopy (VPSEM and energy dispersive X-ray (EDX spectrometer were used to examine the surface morphology and elemental profile of the modified electrode, respectively. Cyclic voltammetry showed significant enhancement in peak current for the determination of paracetamol at the SWCNT/Ni-modified electrode. A linear calibration curve was obtained for the paracetamol concentration between 0.05 and 0.50 mM. The SWCNT/Ni/GCE displayed a sensitivity of 64 mA M−1 and a detection limit of 1.17 × 10−7 M in paracetamol detection. The proposed electrode can be applied for the determination of paracetamol in real pharmaceutical samples with satisfactory performance. Results indicate that electrodes modified with SWCNT and nickel nanoparticles exhibit better electrocatalytic activity towards paracetamol.

GUIDELINES FOR PARACETAMOL POISONING TREATMENT

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Lucija Sarc

2014-04-01

Full Text Available Paracetamol overdose results in an accumulation of the reactive, hepatotoxic metabolite N-acetyl-p-benzoquinoneimin (NAPKQI which can cause serious liver injury. Recognition of paracetamol overdose, hepatotoxicity risk estimation and early treatment are crutial in paracetamol poisoniong management. In ingestion of potential hepatotoxic dose of paracetamol decontamination and early treatment with N-acetylcysteine (NAC are indicated. Both, 20-hours intravenous and 72-hurs oral regimes of NAC administration are successful. By antidote regime selection we should consider patient condition and time after paracetamol overdose. In severe hepatotoxicity, criteria for liver transplantation should be regularly evaluated and mechanisms for liver transplantation must be activated in time. 

Effect of dental restorative materials on total antioxidant capacity and calcium concentration of unstimulated saliva.

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Ramezani, Gholam H; Moghadam, Mona-Momeni; Saghiri, Mohammad-Ali; Garcia-Godoy, Franklin; Asatourian, Armen; Aminsobhani, Mohsen; Scarbecz, Mark; Sheibani, Nader

2017-01-01

To evaluate the effect of dental amalgam and composite restorations on total antioxidant capacity (TAC) and calcium (Ca) ion concentration of unstimulated saliva. Forty-eight children aged 6-10 years selected and divided into three groups of sixteen (8 males, 8 females). In group A and B, samples consisted of two class II dental composite or amalgam restorations, while in group C samples were caries-free (control group). Unstimulated saliva from all samples was collected and TAC was measured by spectrophotometry using an adaptation of 2, 2'-azino-di-(3-ethylbenzthiazoline-6-sulphonate) (ABTS) assay. The Ca ion level was estimated by an auto- analyzer. Data were analyzed with one- and two-way ANOVA test, at a p difference between groups ( p differences within and between groups ( p Gender is an effective factor in changes induced in oral cavity as females showed more emphatic reaction to dental filling materials than males. Patients who have dental restorations, especially dental composites, should pay more attention to their dental hygiene, because dental restorations can increase oxidative stress and decrease Ca ion level in saliva, which might jeopardize remineralization process of tooth structures after demineralization. Key words: Amalgam, caries, composite, saliva, total antioxidant capacity.

Cerebellar level of neurotransmitters in rats exposed to paracetamol during development.

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Blecharz-Klin, Kamilla; Joniec-Maciejak, Ilona; Jawna-Zboińska, Katarzyna; Pyrzanowska, Justyna; Piechal, Agnieszka; Wawer, Adriana; Widy-Tyszkiewicz, Ewa

2016-12-01

The present study was designed to clarify the effect of prenatal and postnatal paracetamol administration on the neurotransmitter level and balance of amino acids in the cerebellum. Biochemical analysis to determine the concentration of neurotransmitters in this brain structure was performed on two-month-old Wistar male rats previously exposed to paracetamol in doses of 5 (P5, n=10) or 15mg/kg (P15, n=10) throughout the entire prenatal period, lactation and until the completion of the second month of life, when the experiment was terminated. Control animals were given tapped water (Con, n=10). The cerebellar concentration of monoamines, their metabolites and amino acids were assayed using High Performance Liquid Chromatography (HPLC). The present experiment demonstrates that prenatal and postnatal paracetamol exposure results in modulation of cerebellar neurotransmission with changes concerning mainly 5-HIAA and MHPG levels. The effect of paracetamol on monoaminergic neurotransmission in the cerebellum is reflected by changes in the level of catabolic end-products of serotonin (5-HIAA) and noradrenaline (MHPG) degradation. Further work is required to define the mechanism of action and impact of prenatal and postnatal exposure to paracetamol in the cerebellum and other structures of the central nervous system (CNS). Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Diffusion coefficients of paracetamol in aqueous solutions

International Nuclear Information System (INIS)

Ribeiro, Ana C.F.; Barros, Marisa C.F.; Veríssimo, Luís M.P.; Santos, Cecilia I.A.V.; Cabral, Ana M.T.D.P.V.; Gaspar, Gualter D.; Esteso, Miguel A.

2012-01-01

Highlights: ► Mutual diffusion coefficients of paracetamol in aqueous dilute solutions. ► Influence of the thermodynamic factors on the variation of their mutual diffusion coefficients. ► Estimation of the mutual limiting diffusion coefficients of the molecular, D m 0 , and ionized forms, D ± 0 , of this drug. - Abstract: Binary mutual diffusion coefficients measured by the Taylor dispersion method, for aqueous solutions of paracetamol (PA) at concentrations from (0.001 to 0.050) mol·dm −3 at T = 298.15 K, are reported. From the Nernst–Hartley equation and our experimental results, the limiting diffusion coefficient of this drug and its thermodynamic factors are estimated, thereby contributing in this way to a better understanding of the structure of such systems and of their thermodynamic behaviour in aqueous solution at different concentrations.

Interventions for paracetamol (acetaminophen) overdose

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Chiew, Angela L; Gluud, Christian; Brok, Jesper

2018-01-01

BACKGROUND: Paracetamol (acetaminophen) is the most widely used non-prescription analgesic in the world. Paracetamol is commonly taken in overdose either deliberately or unintentionally. In high-income countries, paracetamol toxicity is a common cause of acute liver injury. There are various...... of paracetamol. Acetylcysteine should be given to people at risk of toxicity including people presenting with liver failure. Further randomised clinical trials with low risk of bias and adequate number of participants are required to determine which regimen results in the fewest adverse effects with the best...... was abandoned due to low numbers recruited), assessing several different interventions in 700 participants. The variety of interventions studied included decontamination, extracorporeal measures, and antidotes to detoxify paracetamol's toxic metabolite; which included methionine, cysteamine, dimercaprol...

Erosion protection conferred by whole human saliva, dialysed saliva, and artificial saliva

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Baumann, T.; Kozik, J.; Lussi, A.; Carvalho, T. S.

2016-10-01

During dental erosion, tooth minerals are dissolved, leading to a softening of the surface and consequently to irreversible surface loss. Components from human saliva form a pellicle on the tooth surface, providing some protection against erosion. To assess the effect of different components and compositions of saliva on the protective potential of the pellicle against enamel erosion, we prepared four different kinds of saliva: human whole stimulated saliva (HS), artificial saliva containing only ions (AS), human saliva dialysed against artificial saliva, containing salivary proteins and ions (HS/AS), and human saliva dialysed against deionised water, containing only salivary proteins but no ions (HS/DW). Enamel specimens underwent four cycles of immersion in either HS, AS, HS/AS, HS/DW, or a humid chamber (Ctrl), followed by erosion with citric acid. During the cycling process, the surface hardness and the calcium released from the surface of the specimens were measured. The different kinds of saliva provided different levels of protection, HS/DW exhibiting significantly better protection than all the other groups (p < 0.0001). Different components of saliva, therefore, have different effects on the protective properties of the pellicle and the right proportions of these components in saliva are critical for the ability to form a protective pellicle.

Randomized comparative trial of efficacy of paracetamol, ibuprofen and paracetamol-ibuprofen combination for treatment of febrile children

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Falgun Indravadan Vyas

2014-01-01

Full Text Available Objective: Paracetamol and ibuprofen are widely used for fever in children as monotherapy and as combined therapy. None of the treatments is proven clearly superior to others. Hence, the study was planned to compare the efficacy of paracetamol, ibuprofen and paracetamol-ibuprofen combination for treatment of febrile children. Materials and Methods: This was an investigator blind, randomized, comparative, parallel clinical trial conducted in 99 febrile children, 6 months to 12 years of age, allocated to three groups. First group received paracetamol 15 mg/kg, second group received ibuprofen 10 mg/kg and third group received both paracetamol and ibuprofen, all as a single dose by the oral route. Patients were followed-up at intervals of 1, 2, 3 and 4 h post dose by tympanic thermometry. Results: Mean tympanic temperature after 4 h of drug administration was significantly lower in the combination group compared with paracetamol group (P < 0.05; however, the difference was not clinically significant (<1΀C. The rate of fall of temperature was highest in the combination group. Number of afebrile children any time post dose until 4 h was highest in the combination group. Difference between combination and paracetamol was significant for the 1 st h (P = 0.04. Highest fall of temperature was noted in the 1 st h of drug administration in all the groups. No serious adverse events were observed in any of the groups. Conclusion: Paracetamol and ibuprofen combination caused quicker temperature reduction than either paracetamol or ibuprofen alone. If quicker reduction of body temperature is the desired goal of therapy, the use of combination of paracetamol + ibuprofen may be advocated.

Accuracy of the paracetamol-aminotransferase multiplication product to predict hepatotoxicity in modified-release paracetamol overdose.

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Wong, Anselm; Sivilotti, Marco L A; Graudins, Andis

2017-06-01

The paracetamol-aminotransferase multiplication product (APAP × ALT) is a risk predictor of hepatotoxicity that is somewhat independent of time and type of ingestion. However, its accuracy following ingestion of modified-release formulations is not known, as the product has been derived and validated after immediate-release paracetamol overdoses. The aim of this retrospective cohort study was to evaluate the accuracy of the multiplication product to predict hepatotoxicity in a cohort of patients with modified-release paracetamol overdose. We assessed all patients with modified-release paracetamol overdose presenting to our hospital network from October 2009 to July 2016. Ingestion of a modified-release formulation was identified by patient self-report or retrieval of the original container. Hepatotoxicity was defined as peak alanine aminotransferase ≥1000 IU/L, and acute liver injury (ALI) as a doubling of baseline ALT to more than 50 IU/L. Of 1989 paracetamol overdose presentations, we identified 73 modified-release paracetamol exposures treated with acetylcysteine. Five patients developed hepatotoxicity, including one who received acetylcysteine within eight hours of an acute ingestion. No patient with an initial multiplication product paracetamol overdose treated with acetylcysteine, the paracetamol-aminotransferase multiplication product demonstrated similar accuracy and temporal profile to previous reports involving mostly immediate-release formulations. Above a cut-point of 10,000 mg/L × IU/L, it was very strongly associated with the development of acute liver injury and hepatotoxicity, especially when calculated more than eight hours post-ingestion. When below 1500 mg/L × IU/L the likelihood of developing hepatotoxicity was very low. Persistently high serial multiplication product calculations were associated with the greatest risk of hepatotoxicity.

Population prevalence of high dose paracetamol in dispensed paracetamol/opioid prescription combinations: an observational study

Science.gov (United States)

2012-01-01

Background Paracetamol (acetaminophen) is generally considered a safe medication, but is associated with hepatotoxicity at doses above doses of 4.0 g/day, and even below this daily dose in certain populations. Methods The Nova Scotia Prescription Monitoring Program (NSPMP) in the Canadian province of Nova Scotia is a legislated organization that collects dispensing information on all out-of-hospital prescription controlled drugs dispensed for all Nova Scotia residents. The NSPMP provided data to track all paracetamol/opioids redeemed by adults in Nova Scotia, from July 1, 2005 to June 30, 2010. Trends in the number of adults dispensed these prescriptions and the numbers of prescriptions and tablets dispensed over this period were determined. The numbers and proportions of adults who filled prescriptions exceeding 4.0 g/day and 3.25 g/day were determined for the one-year period July 1, 2009 to June 30, 2010. Data were stratified by sex and age (paracetamol/opioid prescription was lower in each successive one-year period. From July 2009 to June 2010, one in 12 adults (n = 59,197) filled prescriptions for over 13 million paracetamol/opioid tablets. Six percent (n = 3,786) filled prescriptions that exceeded 4.0 g/day and 18.6% (n = 11,008) exceeded 3.25 g/day of paracetamol at least once. These findings exclude non-prescription paracetamol and paracetamol–only prescribed medications. Conclusions A substantial number of individuals who redeem prescriptions for paracetamol/opioid combinations may be at risk of paracetamol-related hepatotoxicity. Healthcare professionals must be vigilant when prescribing and dispensing these medications in order to reduce the associated risks. PMID:22709372

Simultaneous determination of paracetamol, 4-Aminophenol, 4-Chloroacetanilid, Benzyl alcohol,Benzaldehyde and EDTA by HPLC methodin paracetamol injection ampoule

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Ali Merrikhi Khosroshahi

2016-06-01

Full Text Available Paracetamol that is known as acetaminophen have the most consume as an analgesic and antipyretic drug in the world. That is formulated in single compound or mixture at many forms such as tablets, syrups, suspensions and drops. The last form is intravenous injections. Paracetamol derived from 4-minophenol which is synthesized by acylated the P-acetaminophenol and acetic anhydride. 4-aminophenol is the main impurity at manufacturing of paracetamol which could produce by hydrolysis during storage or synthesis under normal conditions (temperature, pH, etc.. Also, 4-chloroacetanilid may be observed as an impurity in the raw material of paracetamol synthesis. Benzyl alcohol is a preservative that used in Paracetamol for injection. It will be very important if there are analytical techniques to measuring paracetamol and its degradation products accurately and easily. Undoubtedly the most important and widely used, separation technique is chromatography. There are several reports about separation and quantitative determination of paracetamol lonely or simultaneous determination of paracetamol and 4-aminophenol. In this paper investigated simultaneous determination of paracetamol, 4-aminophenol, 4-chloroacetanilid, benzyl alcohol, benzaldehyde, and EDTA in paracetamol for injection ampoules by high performance liquid chromatography. By changing the ratio of mixing methanol and acetonitrile as mobile phase at the wavelength of 215 nm and pH=3 separation of all compounds were completely done.

Quality control of the paracetamol drug by chemometrics and imaging spectroscopy in the near infrared region

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Baptistao, Mariana; Rocha, Werickson Fortunato de Carvalho; Poppi, Ronei Jesus

2011-09-01

In this work, it was used imaging spectroscopy and chemometric tools for the development and analysis of paracetamol and excipients in pharmaceutical formulations. It was also built concentration maps to study the distribution of the drug in the tablets surface. Multivariate models based on PLS regression were developed for paracetamol and excipients concentrations prediction. For the construction of the models it was used 31 samples in the tablet form containing the active principle in a concentration range of 30.0-90.0% (w/w) and errors below to 5% were obtained for validation samples. Finally, the study of the distribution in the drug was performed through the distribution maps of concentration of active principle and excipients. The analysis of maps showed the complementarity between the active principle and excipients in the tablets. The region with a high concentration of a constituent must have, necessarily, absence or low concentration of the other one. Thus, an alternative method for the paracetamol drug quality monitoring is presented.

Treatment with paracetamol in infants

DEFF Research Database (Denmark)

Arana, A; Morton, N S; Hansen, Tom Giedsing

2001-01-01

Paracetamol (N-acetyl-p-amino-phenol) or acetaminophen has become the most widely used analgesic and antipyretic in children. However, there is a wide discrepancy between the extent to which paracetamol is used and the limited available pharmacological data in small infants. The purpose...... of this article is to present a review of the current literature regarding the use of paracetamol in neonates and infants with a particular emphasis on pharmacological issues....

Characteristics and outcomes of paracetamol poisoning cases at a general hospital in Northern Malaysia.

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Mohd Zain, Z; Fathelrahman, A I; Ab Rahman, A F

2006-02-01

Paracetamol is available as an over-the-counter medication in many countries including Malaysia. This drug has been implicated in many poisoning cases admitted to hospitals throughout the country. We conducted a three-year retrospective review of 165 medical records of patients admitted to the Penang General Hospital for acute paracetamol poisoning. Cases were identified according to the discharge diagnosis documented in their medical records. Acute paracetamol poisoning occurred in all major ethnic groups. About 70 percent of our patients were female. There was minimal involvement of children. Admissions were more likely to be due to deliberate ingestions rather than accidental poisoning. In most cases, serum concentrations data plotted on the Rumack-Matthew nomogram predicted the majority of cases to be unlikely to be hepatotoxic, which were consistent with their mild clinical courses. Patients who acutely ingested more than 140 mg/kg or predicted to be hepatotoxic, based on their serum concentrations, had a significantly longer hospital stay. Although acute paracetamol poisoning was common, the outcome was generally good.

Toxicological effects of paracetamol on the clam Ruditapes philippinarum: exposure vs recovery.

Science.gov (United States)

Nunes, Bruno; Nunes, Joana; Soares, Amadeu M V M; Figueira, Etelvina; Freitas, Rosa

2017-11-01

Exposure of wild organisms to anthropogenic substances never follows a definite time-course and pulsed events can often determine biological responses to such chemicals, confounding the interpretation of toxicological data. This is the case of specific chemicals such as pharmaceutical drugs, which are commonly released by sewage systems into sensitive areas, including estuaries. The presence and amount of these chemicals in the wild can be modulated by events such as dilution due to heavy rain, floods, or by varying patterns of domestic water use (daily vs. seasonal). The present study aimed to obtain additional data about the toxicity of paracetamol towards the marine clam species Ruditapes philippinarum, following realistic modes of exposure. Thus, the toxicity assessment was made after an acute exposure to different concentrations of paracetamol, followed by a recovery period. The adopted toxicological endpoints included energy-related parameters (glycogen content, GLY; protein content, PROT; electron transport system activity, ETS), activity of antioxidant and biotransformation enzymes (superoxide dismutase, SOD; glutathione peroxidase, GPx; Glutathione-S-transferases, GSTs), levels of reduced glutathione (GSH), neurotoxicity (cholinesterases activity, ChEs), and indicators of oxidative damage (lipid peroxidation, LPO). The here obtained results showed an increase in SOD and GPx activities after exposure. In organisms exposed to the highest concentration tested it was also possible to observe a significant increase in GSTs activity. However, these alterations in the antioxidant defence system were not able to prevent the occurrence of oxidative stress in exposed organisms. Furthermore, exposure to paracetamol induced neurotoxicity in clams, with a concentration-dependent ChEs inhibition along the exposure concentrations. Exposure to paracetamol also led to an increase of GLY content which resulted from metabolic activity depression along the increasing exposure

Release Properties of Paracetamol Granulationa Formulated with ...

African Journals Online (AJOL)

Theobroma cacao gum, TCG was derived as a dry powder from fresh fruits of Theobroma cacao. Various granulations of paracetamol were prepared with TCG at the concentrations of 0.5 – 4% w/w. Similar formulations were prepared using sodium carboxymethyl cellulose, SCMC and acacia gums as standards. In each ...

What is the clinical significance of 5-oxoproline (pyroglutamic acid) in high anion gap metabolic acidosis following paracetamol (acetaminophen) exposure?

Science.gov (United States)

Liss, D B; Paden, M S; Schwarz, E S; Mullins, M E

2013-11-01

Paracetamol (acetaminophen) ingestion is the most frequent pharmaceutical overdose in the developed world. Metabolic acidosis sometimes occurs, but the acidosis is infrequently persistent or severe. A growing number of case reports and case series describe high anion gap metabolic acidosis (HAGMA) following paracetamol exposure with subsequent detection or measurement of 5-oxoproline (also called pyroglutamic acid) in blood, urine, or both. Typically 5-oxoprolinuria or 5-oxoprolinemia occurs in the setting of inborn genetic errors in glutathione metabolism. It is unknown whether 5-oxoprolinemia in the setting of paracetamol exposure reflects an acquired or transient derangement of glutathione metabolism or previously unrecognized genetic defects. We reviewed the published cases of 5-oxoprolinemia or 5-oxoprolinuria among patients with HAGMA in the setting of paracetamol exposure. Our goal was to identify any consistent features that might increase our understanding of the pathophysiology, diagnosis, and treatment of similar cases. We searched the medical literature using PUBMED and EMBASE from inception to 28 August 2013 applying search terms ("oxoproline" OR "pyroglutamic acid" AND "paracetamol" OR "acetaminophen"). The intersection of these two searches returned 77 articles, of which 64 involved human subjects and were in English. Two articles, one each in Spanish and Dutch, were reviewed. An additional Google Scholar search was done with the same terms. We manually searched the reference lists of retrieved articles to identify additional four relevant articles. We focused on articles including measured 5-oxoproline concentrations in urine or blood. Twenty-two articles included quantified 5-oxoproline concentrations. Several additional articles mentioned only qualitative detection of 5-oxoproline in urine or blood without concentrations being reported. Our manual reference search yielded four additional articles for a total of 24 articles describing 43 patients

Leukosit Ayam Pedaging setelah Diberikan Paracetamol

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. Suriansyah

2016-03-01

Full Text Available Penelitian ini bertujuan untuk mengetahui profil hematologi (total leukosit dan diferensial leukosit pada ayam pedaging yang diberikan paracetamol dalam pakan mulai umur 14 – 35 hari, Penelitian ini menggunakan Rancangan acak lengkap yaitu P0 (kelompok ayam pedaging yang hanya diberi pakan standar SB-11, P? (pakan standar SB-11 dan paracetamol 1 g/kg pakan, P? (pakan standar SB-11 dan paracetamol 2 g/kg pakan, P? (pakan standar SB-11 dan paracetamol 4 g/kg pakan masing-masing kelompok terdiri dari enam ekor ayam pedaging. Pengambilan darah pada vena brachialis dilakukan sebelum diberikan perlakuan dan pada hari ke 21 setelah diberikan perlakuan. Hasil penelitian menunjukkan bahwa pemberian paracetamol dosis 1-4 g/kg pakan tidak berpengaruh nyata terhadap total leukosit (P>0,05 akan tetapi hanya berpengaruh nyata terhadap monosit (P

The influence of pilocarpine and biperiden on pH value and calcium, phosphate, and bicarbonate concentrations in saliva during and after radiotherapy for head and neck cancer.

Science.gov (United States)

Rode, M; smid, L; Budihna, M; Gassperssic, D; Rode, M; Soba, E

2001-11-01

The purpose of the present study was to investigate the influence of parasympathomimetic pilocarpine and anticholinergic biperiden on salivation, pH value, and calcium, phosphate, and bicarbonate concentrations in saliva in patients irradiated for malignant tumors of the head and neck region. Sixty-nine patients were randomly assigned into 3 groups. Group A consisted of patients receiving pilocarpine, group B of those who were receiving biperiden during radiotherapy and pilocarpine for 6 weeks after its completion, and group C comprised patients receiving neither of the mentioned drugs. The quantity of secreted unstimulated saliva, its pH value, as well as calcium, phosphate, and bicarbonate concentrations in saliva were measured before the beginning of radiotherapy, after 30 Gy of irradiation, at completed irradiation, and 3, 6, and 12 months after completion of radiotherapy. Saliva secretion was found to be the least affected in the group of patients receiving biperiden throughout the course of radiotherapy. One year after completion of therapy, the quantity of secreted saliva could only be measured in the patients receiving biperiden during radiotherapy; it amounted to 16% of the average initial quantity of saliva secreted before the beginning of irradiation. In all 3 groups of patients, mean pH value decreased during radiotherapy and started to increase again after completion of irradiation. In group B the decrease in pH value after radiotherapy was statistically significantly smaller than that in group C (P =.01). During and after irradiation, calcium concentration was increased in all 3 groups of patients. Phosphate concentration decreased during radiotherapy in all 3 groups. In group B it started to increase again 3 months after completion of radiotherapy. Bicarbonate concentration showed a slight increase during radiotherapy and started to decrease again after completion of irradiation. The results of our study indicate that the inhibition of saliva

Paracetamol for feverish children: parental motives and experiences

DEFF Research Database (Denmark)

Jensen, J.F.; Tonnesen, L.L.; Söderström, Margareta

2010-01-01

OBJECTIVE: The sale of paracetamol products for children is increasing, and more children are accidentally given overdoses, even though the use of paracetamol against fever is still under discussion. This study explores Danish parents' use of paracetamol for feverish children and their motives fo...... their GP for advice on fever treatment, paracetamol is sometimes given to children on vague indications. Clearer information for parents on when to give paracetamol as fever treatment may help regulate its use...

Influence of fruit drinks with or without lactobacillus Lp299v on the gastrointestinal uptake of paracetamol in man

DEFF Research Database (Denmark)

Akerman, Ulrika; Edvinsson, Lars

2009-01-01

BACKGROUND: Clinical observations have revealed that patients throw up undigested paracetamol tablets several hours following intake of rosehip drink with Lp299v (Proviva). The purpose of this study was to demonstrate if this translates into altered plasma levels of paracetamol in nineteen healthy...... subjects consuming 200 ml of water, Rose hip drink or Proviva together with 1.5 gram of paracetamol. FINDINGS: The concentration of paracetamol in plasma increased rapidly when the paracetamol-containing tablets were consumed together with water and after 30 minutes a median level of 90 mumol/l was reached...... (a 95% confidence interval of 57,161). The corresponding 30 minutes values of paracetamol levels in the presence of rosehip with or without Lp299v were 0 mumol/l (95% confidence intervals contain only zero for both rosehip treatments). There were significant differences in AUC, maximal paracetamol...

The Assessment of Liver Reserve Function by Spectrophotometry based on Determination of Phenacetin and Paracetamol.

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Ren, Rui; Ma, Yongmei; Ma, Wanshan; Lu, Sumei

2015-01-01

To establish a technical system for assessing liver reserve function based on spectrophotometry by detection of phenacetin and paracetamol in blood samples. Taking detected contents of phenacetin and paracetamol by high performance liquid chromatography (HPLC) as standard, which was proved to be able to detect drug concentrations with high resolution and accuracy, we established a technical system based on the spectrophotometric technique to assay phenacetin and paracetamol, including the color system, the maximum absorption wavelength, the influence factors of color system, and the optimal conditions for hydrolysis. Then we verified our established system compared with that under HPLC by recovery test. This study established a technical system to detect phenacetin and paracetamol in blood samples using spectrophotometry. Mainly, 3 mol/L hydrochloric acid (HCl) was added to samples for hydrolysis for 30 minutes, then, adding 0.02% 1,2-naphthoquinone-4-sulfonate (NQS), 1% cetyltrimethyl ammonium bromide (CTA) and 2% sodium hydroxide (or 3% sodium carbonate) (ratio of 1:6:1:2 or 3), and the absorbance was measured at 500 nm and 570 nm to calculate their concentrations. Using an established spectrophotometric system to detect phenacetin and paracetamol in blood samples could assess liver reserve function, which was proved comparable with HPLC in resolution and repeatability.

First evidence of the conversion of paracetamol to AM404 in human cerebrospinal fluid

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Sharma CV

2017-11-01

Full Text Available Chhaya V Sharma,1 Jamie H Long,2 Seema Shah,1 Junia Rahman,1 David Perrett,3 Samir S Ayoub,4 Vivek Mehta1 1Pain & Anaesthesia Research Centre, St Bartholomew’s and The Royal London Hospitals, Barts Health NHS Trust, London, UK; 2Barts & The London School of Medicine, Queen Mary University of London, London, UK; 3BioAnalytical Science, Barts & The London School of Medicine, Queen Mary University of London, London, UK; 4School of Health, Sport and Bioscience, Medicines Research Group, University of East London, London, UK Abstract: Paracetamol is arguably the most commonly used analgesic and antipyretic drug worldwide, however its mechanism of action is still not fully established. It has been shown to exert effects through multiple pathways, some actions suggested to be mediated via N-arachidonoylphenolamine (AM404. AM404, formed through conjugation of paracetamol-derived p-aminophenol with arachidonic acid in the brain, is an activator of the capsaicin receptor, TRPV1, and inhibits the reuptake of the endocannabinoid, anandamide, into postsynaptic ­neurons, as well as inhibiting synthesis of PGE2 by COX-2. However, the presence of AM404 in the central nervous system following administration of paracetamol has not yet been demonstrated in humans. Cerebrospinal fluid (CSF and blood were collected from 26 adult male patients between 10 and 211 minutes following intravenous administration of 1 g of paracetamol. Paracetamol was measured by high-performance liquid chromatography with UV detection. AM404 was measured by liquid chromatography-tandem mass spectrometry. AM404 was detected in 17 of the 26 evaluable CSF samples at 5–40 nmol⋅L–1. Paracetamol was measurable in CSF within 10 minutes, with a maximum measured concentration of 60 μmol⋅L–1 at 206 minutes. This study is the first to report on the presence of AM404 in human CSF following paracetamol administration. This may represent an important finding in our understanding of

Manganese concentration in human saliva using NAA

Energy Technology Data Exchange (ETDEWEB)

Lewgoy, Hugo R., E-mail: hugorl@usp.br [Universidade Bandeirante Anhanguera (UNIBAN), Sao Paulo, SP (Brazil); Zamboni, Cibele B.; Medeiros, Ilca M.M.A.; Medeiros, Jose A.G. de [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

2013-07-01

In this investigation the Manganese levels in human whole saliva were determined using Neutron Activation Analysis (NAA) technique for the proposition of an indicative interval. The measurements were performed considering gender and lifestyle factors of Brazilian inhabitants (non-smokers, non-drinkers and no history of toxicological exposure). The results emphasize that the indicative interval is statistically different by gender. These data are useful for identifying or preventing some diseases in the Brazilian population. (author)

Manganese concentration in human saliva using NAA

International Nuclear Information System (INIS)

Lewgoy, Hugo R.; Zamboni, Cibele B.; Medeiros, Ilca M.M.A.; Medeiros, Jose A.G. de

2013-01-01

In this investigation the Manganese levels in human whole saliva were determined using Neutron Activation Analysis (NAA) technique for the proposition of an indicative interval. The measurements were performed considering gender and lifestyle factors of Brazilian inhabitants (non-smokers, non-drinkers and no history of toxicological exposure). The results emphasize that the indicative interval is statistically different by gender. These data are useful for identifying or preventing some diseases in the Brazilian population. (author)

Granule properties of paracetamol made with Bombax ceiba gum ...

African Journals Online (AJOL)

Bombax ceiba gum was extracted from the calyx of the Bombax flower using both hot and cold water extraction method. The gum was used as binder to prepare paracetamol granules in concentrations of 1, 1.5, 2, and 3 %. Acacia gum was used to prepare the standard at the same concentrations. The granule properties of ...

Detection of phencyclidine usage by radioimmunoassay of saliva

International Nuclear Information System (INIS)

McCarron, M.M.; Walberg, C.B.; Soares, J.R.; Gross, S.J.; Baselt, R.C.

1984-01-01

Paired serum and saliva samples, obtained from 100 emergency department patients suspected of phencyclidine (PCP) intoxication, were analyzed using a specific PCP radioimmunoassay (RIA). Seventy-four of the 100 saliva samples and 75 of the paired serum samples were positive for PCP. The final clinical diagnosis was PCP intoxication in 79 cases. Of these, both serum and saliva tests were positive in 70 cases, only serum was positive in two cases, and both serum and saliva samples were negative in seven cases. The concentration of PCP in the samples did not correlate with the severity of PCP intoxication. In the remaining 21 cases, with no clinical evidence of PCP intoxication, PCP assays were negative in both serum and saliva in 17 cases, three patients had positive saliva and serum tests, and one other patient had a positive PCP saliva assay. Thus, saliva would appear to be as reliable as serum as a specimen for PCP analysis

Effects of imatinib mesylate on the pharmacokinetics of paracetamol (acetaminophen) in Korean patients with chronic myelogenous leukaemia.

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Kim, Dong-Wook; Tan, Eugene Y; Jin, Yu; Park, Sahee; Hayes, Michael; Demirhan, Eren; Schran, Horst; Wang, Yanfeng

2011-02-01

The major objective of the present study was to investigate the effect of imatinib on the pharmacokinetics of paracetamol in patients with chronic myelogenous leukaemia (CML). Patients (n = 12) received a single oral dose of acetaminophen 1000 mg on day 1 (control). On days 2-8, imatinib 400 mg was administered daily. On day 8 (treatment), another 1000 mg dose of paracetamol was administered 1 h after the morning dose of imatinib 400 mg. Blood and urine samples were collected for bioanalytical analyses. The area under the plasma concentration-time curve (AUC) for paracetamol, paracetamol glucuronide and paracetamol sulphate under control conditions was similar to that after treatment with imatinib; the 90% confidence interval of the log AUC ratio was within 0.8 to 1.25. Urinary excretion of paracetamol, paracetamol glucuronide and paracetamol sulphate was also unaffected by imatinib. The pharmacokinetics of paracetamol and imatinib in Korean patients with CML were similar to previous pharmacokinetic results in white patients with CML. Co-administration of a single dose of paracetamol and multiple doses of imatinib was well tolerated and safety profiles were similar to those of either drug alone. The pharmacokinetics of paracetamol and its major metabolites in the presence of imatinib were similar to those of the control conditions and the combination was well tolerated. These findings suggest that imatinib can be safely administered with paracetamol without dose adjustment of either drug. © 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.

Degradation of paracetamol and other constituents in Perfalgan®

African Journals Online (AJOL)

was used to calculate the penetration of paracetamol in Perfalgan® into the lipid layer. Results: The ..... Molar ratio derived by 1H NMR. Molecular weight .... injection volume and sample concentration were used in all the experiments this is ...

A novel approach for estimating ingested dose associated with paracetamol overdose.

Science.gov (United States)

Zurlinden, Todd J; Heard, Kennon; Reisfeld, Brad

2016-04-01

In cases of paracetamol (acetaminophen, APAP) overdose, an accurate estimate of tissue-specific paracetamol pharmacokinetics (PK) and ingested dose can offer health care providers important information for the individualized treatment and follow-up of affected patients. Here a novel methodology is presented to make such estimates using a standard serum paracetamol measurement and a computational framework. The core component of the computational framework was a physiologically-based pharmacokinetic (PBPK) model developed and evaluated using an extensive set of human PK data. Bayesian inference was used for parameter and dose estimation, allowing the incorporation of inter-study variability, and facilitating the calculation of uncertainty in model outputs. Simulations of paracetamol time course concentrations in the blood were in close agreement with experimental data under a wide range of dosing conditions. Also, predictions of administered dose showed good agreement with a large collection of clinical and emergency setting PK data over a broad dose range. In addition to dose estimation, the platform was applied for the determination of optimal blood sampling times for dose reconstruction and quantitation of the potential role of paracetamol conjugate measurement on dose estimation. Current therapies for paracetamol overdose rely on a generic methodology involving the use of a clinical nomogram. By using the computational framework developed in this study, serum sample data, and the individual patient's anthropometric and physiological information, personalized serum and liver pharmacokinetic profiles and dose estimate could be generated to help inform an individualized overdose treatment and follow-up plan. © 2015 The British Pharmacological Society.

Effect of Solution pH on the Adsorption of Paracetamol on Chemically Modified Activated Carbons

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Valentina Bernal

2017-06-01

Full Text Available Paracetamol adsorption in acidic, neutral and basic media on three activated carbons with different chemistry surfaces was studied. A granular activated carbon (GAC was prepared from coconut shell; starting from this sample, an oxidized activated carbon (GACo was obtained by treating the GAC with a boiling solution of 6 M nitric acid, so to generate a greater number of oxygenated surface groups. In addition, a reduced activated carbon (GACr was obtained by heating the GAC at 1173 K, to remove the oxygenated surface groups. Paracetamol adsorption was higher for GACr due to the lower presence of oxygenated surface functional groups. Moreover, adsorption was highest at neutral pH. The magnitude of the interactions between paracetamol molecules and activated carbons was studied by measuring the immersion enthalpies of activated carbons in solution of paracetamol at different concentrations and pH values and by calculating the interaction enthalpy. The highest value was obtained for GACr in a paracetamol solution of 1000 mg L−1 at pH 7, confirming that paracetamol adsorption is favoured on basic activated carbons at pH values near to neutrality. Finally, the Gibbs energy changes confirmed the latter result, allowing explaining the different magnitudes of the interactions between paracetamol and activated carbons, as a function of solution pH.

Effect of quercetin on paracetamole-induced liver disjunction in irradiated rats

International Nuclear Information System (INIS)

Hedayat, I.S.

2005-01-01

Nowadays, increasing attention has been given to the role of free radicals generated through oxidation stress. Persons subjected to radiation, such as radiotherapy, consuming analgesic drugs such as paracetamole which accumulates at relatively high concentration in liver, are in need to be investigated to explore the synergetic effects of these stresses. Many radical scavengers, interestingly naturally occurring antioxidants, have been found to be effective in inhibiting the oxidative damage Quercetin, the well known phenolic compound widely present in the plant kingdom, has been investigated for its possible protection effect against gamma irradiation and paracetamole-induced hepatic damage. Data revealed serious effects of oral administration of sublethal dose of paracetamole (500 mg/kg) and/or exposure to 6 Gy whole body gamma irradiation on liver. This damage is reflected by increased hepatic levels of MDA, carbonyl content and ALT activity, associated by decrease in hepatic SOD, catalase and GSH when compared with respective control values. The combination of quercetin with paracetamole and/or gamma irradiation have clearly reduced liver damage. It was noticed that the restoration of peroxides and carbonyls rates has occurred. Quercetin seems to act by activation of the turnover of SOD, catalase and GSH and permitting the capitation of reactive metabolites of paracetamole as well as its ability in quenching free radicals induced by exposure of rats to gamma irradiation, thus improving regeneration in the biological tissues

Developmental exposure to paracetamol causes biochemical alterations in medulla oblongata.

Science.gov (United States)

Blecharz-Klin, Kamilla; Joniec-Maciejak, Ilona; Jawna, Katarzyna; Pyrzanowska, Justyna; Piechal, Agnieszka; Wawer, Adriana; Widy-Tyszkiewicz, Ewa

2015-09-01

The effect and safety of prenatal and early life administration of paracetamol - routinely used over-the-counter antipyretic and analgesic medication on monoamines content and balance of amino acids in the medulla oblongata is still unknown. In this study we have determined the level of neurotransmitters in this structure in two-month old Wistar male rats exposed to paracetamol in the dose of 5 (P5, n=10) or 15mg/kg b.w. (P15, n=10) during prenatal period, lactation and till the end of the second month of life. Control group received drinking water (Con, n=10). Monoamines, their metabolites and amino acids concentration in medulla oblongata of rats were determined using high performance liquid chromatography (HPLC) in 60 postnatal day (PND60). This experiment shows that prenatal and early life paracetamol exposure modulates neurotransmission associated with serotonergic, noradrenergic and dopaminergic system in medulla oblongata. Reduction of alanine and taurine levels has also been established. Copyright © 2015 Elsevier B.V. All rights reserved.

Increased availability of paracetamol in Sweden and incidence of paracetamol poisoning: using laboratory data to increase validity of a population-based registry study.

Science.gov (United States)

Gedeborg, Rolf; Svennblad, Bodil; Holm, Lennart; Sjögren, Hans; Bardage, Carola; Personne, Mark; Sjöberg, Gunilla; Feltelius, Nils; Zethelius, Björn

2017-05-01

To estimate the incidence trend and outcome of paracetamol poisoning, in relation to increased availability of paracetamol from non-pharmacy outlets in 2009. Patients' serum paracetamol results over 14 years (2000-2013) from 20 (out of 21) regions in Sweden were linked to national registers of hospital care, cause of death, and prescriptions. Paracetamol poisonings were defined by serum paracetamol levels, hospital diagnoses, or cause of death. The change in incidence of poisonings following increased availability of paracetamol was analysed by using segmental regression of time series. Of the 12 068 paracetamol poisonings, 85% were classified as intentional self-harm. Following increased availability from non-pharmacy outlets, there was a 40.5% increase in the incidence of paracetamol poisoning, from 11.5/100 000 in 2009 to 16.2/100 000 in 2013. Regression analyses indicated a change in the trend (p paracetamol did not influence the result. All-cause mortality at 30 days (3.2%) did not change over time. The incidence of paracetamol poisoning in Sweden has increased since 2009, contrasting the decreased incidence in the period of 2007-2009. The change in trend was temporally associated with the introduction of availability of paracetamol from non-pharmacy outlets but did not appear to be related to sales volume of paracetamol or general trends in self-harm or suicides. © 2017 Commonwealth of Australia. Pharmacoepidemiology and Drug Safety © 2017 John Wiley & Sons, Ltd. © 2017 Commonwealth of Australia. Pharmacoepidemiology and Drug Safety © 2017 John Wiley & Sons, Ltd.

Efficacy of paracetamol on patent ductus arteriosus closure may be dose dependent: evidence from human and murine studies.

Science.gov (United States)

El-Khuffash, Afif; Jain, Amish; Corcoran, David; Shah, Prakesh S; Hooper, Christopher W; Brown, Naoko; Poole, Stanley D; Shelton, Elaine L; Milne, Ginger L; Reese, Jeff; McNamara, Patrick J

2014-09-01

We evaluated the clinical effectiveness of variable courses of paracetamol on patent ductus arteriosus (PDA) closure and examined its effect on the in vitro term and preterm murine ductus arteriosus (DA). Neonates received one of the following three paracetamol regimens: short course of oral paracetamol (SCOP), long course of oral paracetamol (LCOP), and intravenous paracetamol (IVP) for 2-6 d. Pressure myography was used to examine changes in vasomotor tone of the preterm and term mouse DA in response to paracetamol or indomethacin. Their effect on prostaglandin synthesis by DA explants was measured by mass spectroscopy. Twenty-one preterm infants were included. No changes in PDA hemodynamics were seen in SCOP infants (n = 5). The PDA became less significant and eventually closed in six LCOP infants (n = 7). PDA closure was achieved in eight IVP infants (n = 9). On pressure myograph, paracetamol induced a concentration-dependent constriction of the term mouse DA, up to 30% of baseline (P 1 µmol/l. Indomethacin induced greater DA constriction and suppression of prostaglandin synthesis (P closure may depend on the duration of treatment and the mode of administration. Paracetamol is less potent than indomethacin for constriction of the mouse DA in vitro.

Lack of respiratory depression in paracetamol-codeine combination overdoses.

Science.gov (United States)

Heppell, Simon P E; Isbister, Geoffrey K

2017-06-01

Codeine containing analgesics are commonly taken in overdose, but the frequency of respiratory depression is unknown. We investigated whether paracetamol-codeine combination overdoses caused respiratory depression more than paracetamol alone. We reviewed deliberate self-poisoning admissions with paracetamol (>2 g) and paracetamol-codeine combinations presenting to a tertiary toxicology unit (1987-2013). Demographic information, clinical effects, treatment (naloxone, length of stay [LOS], mechanical ventilation) were extracted from a prospective database. Primary outcome was naloxone requirement or ventilation for respiratory depression. From 4488 presentations, 1376 admissions were included with paracetamol alone (929), paracetamol-codeine combinations (346) or paracetamol-codeine-doxylamine combinations (101) without co-ingestants. Median age was 23 years (12-89 years); 1002 (73%) were female. Median dose was 12 g (interquartile range [IQR]: 7.5-20 g). Median LOS was 16 h (IQR: 6.5-27 h) and 564 (41%) were given acetylcysteine. Significantly larger paracetamol doses were ingested and more acetylcysteine given in paracetamol alone versus paracetamol combination overdoses. Seven out of 1376 patients were intubated or received naloxone (0.5%; 95% CI: 0.2-1.1%), three intubated, three given naloxone and one both. Three out of 929 patients ingesting paracetamol alone (0.3%; 95% CI: 0.1-1%) required intubation or naloxone, compared to two out of 346 ingesting paracetamol-codeine combinations (0.6%; 95% CI: 0.1-2.3%; absolute difference, 0.26%; 95% CI: -0.7-1.2%; P = 0.62). Two out of 101 patients ingesting paracetamol-codeine-doxylamine combinations (2%; 95% CI: 0.3-8%) required intubation or naloxone. Four patients were intubated for reasons other than respiratory depression: hepatotoxicity (2), retrieval (1), no data (1). Two out of 929 (0.2%) paracetamol alone overdoses had a Glasgow coma score depression, with only two given naloxone and none intubated for

Morphological effect of BiVO4 catalysts on degradation of aqueous paracetamol under visible light irradiation.

Science.gov (United States)

Hu, Changying; Xu, Jie; Zhu, Yaqi; Chen, Acong; Bian, Zhaoyong; Wang, Hui

2016-09-01

Morphological effect of bismuth vanadate (BiVO4) on visible light-driven catalytic degradation of aqueous paracetamol was carefully investigated using four monoclinic BiVO4 catalysts. The catalysts with different morphologies were controllably prepared by a hydrothermal method without any additions. The prepared catalysts were fully characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), and UV-Vis diffuse reflectance spectroscopy (DRS). Under the visible light irradiation, these catalysts with different morphology were investigated to degrade aqueous paracetamol contaminant. The degradation effects were evaluated based on the catalyst morphology, solution pH, initial paracetamol concentration, and catalyst dosage. Cube-like BiVO4 powders exhibited excellent photocatalytic performance. The optimal photocatalytic performance of the cube-like BiVO4 in degrading paracetamol was achieved.

One-pot synthesis of a graphene oxide coated with an imprinted sol–gel for use in electrochemical sensing of paracetamole

International Nuclear Information System (INIS)

Luo, Jing; Cong, Jiaojiao; Fang, Ruixue; Fei, Xiaoma; Liu, Xiaoya

2014-01-01

A route is described for the preparation of a composite consisting of graphene oxide and a molecularly imprinted sol–gel polymer (GO/MIPs) through one-pot room temperature polymerization in aqueous solution. The material was obtained by mixing graphene oxide with the monomers (phenyltriethoxysilane and tetramethoxysilane) and the template paracetamole, followed by sol–gel copolymerization and extraction. The monomer and template concentrations and the incubation time were optimized. The composite was characterized by FTIR, TGA, XRD, Raman spectroscopy and SEM. It was then deposited as a thin film acting as a molecular recognition element on a glassy carbon electrode to obtain an electrochemical sensor for paracetamole. The electrode displayed an excellent recognition capacity toward paracetamole compared to its analogs. The peak current is linearly proportional to the concentration of paracetamole in the 0.1 μM to 80 μM range, and the detection limit is 20 nM (at an SNR of 3). Hence, this electrode possesses a wider response range and lower detection limit compared to most previously reported electrochemical sensors for paracetamole. It also exhibits excellent stability and has been successfully used to determine paracetamole in tablets and spiked human urine samples. (author)

Intercalation of paracetamol into the hydrotalcite-like host

International Nuclear Information System (INIS)

Kovanda, František; Maryšková, Zuzana; Kovář, Petr

2011-01-01

Hydrotalcite-like compounds are often used as host structures for intercalation of various anionic species. The product intercalated with the nonionic, water-soluble pharmaceuticals paracetamol, N-(4-hydroxyphenyl)acetamide, was prepared by rehydration of the Mg–Al mixed oxide obtained by calcination of hydrotalcite-like precursor at 500 °C. The successful intercalation of paracetamol molecules into the interlayer space was confirmed by powder X-ray diffraction and infrared spectroscopy measurements. Molecular simulations showed that the phenolic hydroxyl groups of paracetamol interact with hydroxide sheets of the host via the hydroxyl groups of the positively charged sites of Al-containing octahedra; the interlayer water molecules are located mostly near the hydroxide sheets. The arrangement of paracetamol molecules in the interlayer is rather disordered and interactions between neighboring molecules cause their tilting towards the hydroxide sheets. Dissolution tests in various media showed slower release of paracetamol intercalated in the hydrotalcite-like host in comparison with tablets containing the powdered pharmaceuticals. - Graphical abstract: Molecular simulations showed disordered arrangement of paracetamol molecules in the interlayer; most of the interlayer water molecules are located near the hydroxide sheets.▪ Highlights: ► Paracetamol was intercalated in Mg–Al hydrotalcite-like host by rehydration/reconstruction procedure. ► Paracetamol phenolic groups interact with positively charged sites in hydroxide sheets. ► Molecular simulations showed disordered arrangement of guest molecules in the interlayer. ► Slower release of paracetamol intercalated in the hydrotalcite-like host was observed.

Paracetamol for feverish children: parental motives and experiences

DEFF Research Database (Denmark)

Jensen, J.F.; Tonnesen, L.L.; Söderström, Margareta

2010-01-01

OBJECTIVE: The sale of paracetamol products for children is increasing, and more children are accidentally given overdoses, even though the use of paracetamol against fever is still under discussion. This study explores Danish parents' use of paracetamol for feverish children and their motives...

Flujo y concentración de proteínas en saliva total humana Salivary flow rate and protein concentration in human whole saliva

Directory of Open Access Journals (Sweden)

JOSÉ ANTONIO BANDERAS-TARABAY

1997-09-01

Full Text Available Objetivo. Determinar los promedios de flujo salival y la concentración de proteínas totales en una población joven del Estado de México. Material y métodos. Se seleccionaron 120 sujetos a quienes se les colectó saliva total humana (STH no estimulada y estimulada, la cual se analizó por medio de gravimetría y espectrofotometría (LV/LU; se calcularon medidas de tendencia central y de dispersión; posteriormente, se correlacionaron estos datos con los índices CPOD y CPITN. Resultados. Los sujetos estudiados mostraron un promedio de flujo salival (ml/min ± DE en STH no estimulada de 0.397±.26, y en STH estimulada, de 0.973±.53. El promedio en la concentración de proteínas (mg/ml ± DE fue de 1.374±.45 en STH no estimulada y de 1.526±.44 en STH estimulada. Las mujeres presentaron un menor porcentaje de flujo salival y mayor concentración de proteínas. No se observaron correlaciones entre el flujo y la concentración de proteínas totales y el CPOD y CPITN; sin embargo, sí las hubo con otras variables. Conclusiones. Estos hallazgos podrían estar asociados con el grado de nutrición, las características genéticas y los niveles de salud bucal en nuestra población. El presente estudio representa la fase inicial de la creación de una base de datos en sialoquímica, cuya meta será identificar los parámetros que indiquen el riesgo de enfermedades sistémicas o bucodentales.Objective. To determine the average salivary flow rates and total protein concentrations in a population of the State of Mexico. Material and methods. A gravimetric and spectrophotometric analysis was applied to 120 subjects in total resting and stimulated whole saliva and results were correlated with the DMFT and CPITN indexes. Results. Subjects allowed average salivary flow rate (ml/min ± SD in non-stimulated human whole saliva (HWS of 0.397±.26 and in stimulated HWS of 0.973±.53. Average protein concentration was (mg/ml ± SD 1.374±.45 in non

Paracetamol in the environment and its degradation by microorganisms.

Science.gov (United States)

Wu, Shijin; Zhang, Lili; Chen, Jianmeng

2012-11-01

Paracetamol (4'-hydroxyacetanilide, N-acetyl-p-aminophenol, acetaminophen, and paracetamol) is a widely used over-the-counter analgesic and antipyretic drug. Paracetamol and structural analogs are ubiquitous in the natural environment and easily accumulate in aquatic environment, which have been detected in surface waters, wastewater, and drinking water throughout the world. Paracetamol wastewater is mainly treated by chemical oxidation processes. Although these chemical methods may be available for treating these pollutants, the harsh reaction conditions, the generation of secondary pollutants, and the high operational cost associated with these methods have often made them not a desirable choice. Biodegradation of paracetamol is being considered as an environmentally friendly and low-cost option. The goal of this review is to provide an outline of the current knowledge of biodegradation of paracetamol in the occurrence, degrading bacteria, and proposed metabolic/biodegrading pathways, enzymes and possible intermediates. The comprehensive understanding of the metabolic pathways and enzyme systems involved in the utilization of paracetamol means will be helpful for optimizing and allowing rational design of biodegradation systems for paracetamol-contaminated wastewater.

The effect of paracetamol on 5 fluorouracil and bovine serum albumin interaction: A biophysical study

Science.gov (United States)

Dahiya, Vandana; Pal, Samanwita

2018-05-01

Serum Albumin is a major carrier protein and its binding with drugs is important to examine the change in pharmacokinetic properties due to interaction amongst drugs. In the present study we have attempted to understand the relevant drug-drug interaction (DDI) between two common drugs viz, paracetamol, an anti-inflammatory and fluorouracil, an anti-cancer drug. In-vitro spectroscopic methods viz., fluorescence quenching and UV-vis absorption have been employed for the drug-bovine serum albumin (BSA) complexes studies. The binding parameters and quenching constants have been determined for BSA-Paracetamol and BSA-5Fluorouracil complex according to literature models. It is also predicted from the quenching studies that BSA-5Fluorouracil is a stronger complex than BSA-Paracetamol. On the other hand paracetamol can alter binding affinity of 5Fluorouracil towards BSA. Hence it becomes clear that although the drugs could be administered simultaneously but they influence each other's binding with protein in a concentration dependent fashion. Further these results also indicate that availability of free 5Fluorouracil in blood may increase in presence of paracetamol.

Availability of Paracetamol Sold Over-the-Counter in Europe

DEFF Research Database (Denmark)

Morthorst, Britt Reuter; Erlangsen, Annette; Nordentoft, Merete

2018-01-01

Due to the risk of hepatotoxicity when excessive amounts of paracetamol are consumed, Poisons Information Centers (PICs) frequently receive paracetamol-related enquiries. This study examined how widely pack size restrictions of paracetamol sold over-the-counter have been implemented in Europe...... and also availability of paracetamol through non-pharmacy outlets and their possible associations with frequency of poisoning enquiries. A cross-sectional European multicentre questionnaire study was performed using a questionnaire to identify the extent and nature of paracetamol pack size restrictions......, non-pharmacy outlet sales and the frequency of paracetamol-related enquiries to PICs. In total, 21 European countries participated. All PICs provided telephone hotline services. In 14 (67%) countries, pack size restrictions had been implemented in pharmacies (range: 8-30 grams). No significant...

Acute liver failure in a term neonate after repeated paracetamol administration

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Fabio Bucaretchi

2014-03-01

Full Text Available Objective: Severe hepatotoxicity caused by paracetamol is rare in neonates. We report a case of paracetamol-induced acute liver failure in a term neonate. Case description: A 26-day-old boy was admitted with intestinal bleeding, shock signs, slight liver enlargement, coagulopathy, metabolic acidosis (pH=7.21; bicarbonate: 7.1mEq/L, hypoglycemia (18mg/dL, increased serum aminotransferase activity (AST=4,039IU/L; ALT=1,087IU/L and hyperbilirubinemia (total: 9.57mg/dL; direct: 6.18mg/dL after receiving oral paracetamol (10mg/kg/dose every 4 hours for three consecutive days (total dose around 180mg/kg; serum concentration 36-48 hours after the last dose of 77µg/ mL. Apart from supportive measures, the patient was successfully treated with intravenous N-acetylcysteine infusion during 11 consecutive days, and was discharged on day 34. The follow-up revealed full recovery of clinical and of laboratory findings of hepatic function. Comments: The paracetamol pharmacokinetics and pharmacodynamics in neonates and infants differ substantially from those in older children and adults. Despite the reduced rates of metabolism by the P-450 CYP2E1 enzyme system and the increased ability to synthesize glutathione - which provides greater resistance after overdoses -, it is possible to produce hepatotoxic metabolites (N-acetyl-p-benzoquinone that cause hepatocellular damage, if glutathione sources are depleted. Paracetamol clearance is reduced and the half-life of elimination is prolonged. Therefore, a particular dosing regimen should be followed due to the toxicity risk of cumulative doses. This report highlights the risk for severe hepatotoxicity in neonates after paracetamol multiple doses for more than two to three days.

Paracetamol - toxicity and microbial utilization. Pseudomonas moorei KB4 as a case study for exploring degradation pathway.

Science.gov (United States)

Żur, Joanna; Wojcieszyńska, Danuta; Hupert-Kocurek, Katarzyna; Marchlewicz, Ariel; Guzik, Urszula

2018-09-01

Paracetamol, a widely used analgesic and antipyretic drug, is currently one of the most emerging pollutants worldwide. Besides its wide prevalence in the literature only several bacterial strains able to degrade this compound have been described. In this study, we isolated six new bacterial strains able to remove paracetamol. The isolated strains were identified as the members of Pseudomonas, Bacillus, Acinetobacter and Sphingomonas genera and characterized phenotypically and biochemically using standard methods. From the isolated strains, Pseudomonas moorei KB4 was able to utilize 50 mg L -1 of paracetamol. As the main degradation products, p-aminophenol and hydroquinone were identified. Based on the measurements of specific activity of acyl amidohydrolase, deaminase and hydroquinone 1,2-dioxygenase and the results of liquid chromatography analyses, we proposed a mechanism of paracetamol degradation by KB4 strain under co-metabolic conditions with glucose. Additionally, toxicity bioassays and the influence of various environmental factors, including pH, temperature, heavy metals at no-observed-effective-concentrations, and the presence of aromatic compounds on the efficiency and mechanism of paracetamol degradation by KB4 strain were determined. This comprehensive study about paracetamol biodegradation will be helpful in designing a treatment systems of wastewaters contaminated with paracetamol. Copyright © 2018 Elsevier Ltd. All rights reserved.

Changes in the Concentration of Ions in Saliva and Dental Plaque after Application of CPP-ACP with and without Fluoride among 6-9 Year Old Children.

Science.gov (United States)

Poureslami, H; Hoseinifar, Ra; Khazaeli, P; Hoseinifar, Re; Sharifi, H; Poureslami, P

2017-03-01

The casein phospho peptide-amorphous calcium phosphate with or without fluoride (CPP-ACPF and CPP-ACP respectively) are of considerably new materials which are highly recommended for prevention of dental caries. However, there is a shortage in literature on how they affect the ion concentration of saliva or dental plaque. The aim of this study was to evaluate the concentration of calcium, phosphate and fluoride in the plaque and saliva of children with Early Childhood Caries (ECC) after applying the CPP-ACP paste in comparison with the use of CPP-ACPF paste. One ml of un-stimulated saliva of 25 preschool children was collected and then 1 mg of the plaque sample was collected from the buccal surfaces of the two first primary molars on the upper jaw. CPP-ACP as well as CPP-ACPF pastes were applied on the tooth surfaces in two separate steps. In steps, plaque and saliva sampling was performed after 60 minutes. The amount of calcium ions was measured by Atomic Absorption Device and the amount of phosphate and fluoride ions was measured by Ion Chromatography instrument. Data were analyzed using Repeated Measurements ANOVA at a p Application of both CPP-ACPF and CPP-ACP significantly increased the concentration of calcium, phosphate, and fluoride in both saliva and dental plaque. Moreover, significantly higher salivary fluoride concentration was seen after application of CPP-ACPF compared to CPP-ACP. No other significant difference was observed between these two materials. CPP-ACPF can be more useful than CPP-ACP in protecting the primary teeth against caries process, especially when there is poor hygiene.

Paracetamol and salicylic acid removal from contaminated water by microalgae.

Science.gov (United States)

Escapa, C; Coimbra, R N; Paniagua, S; García, A I; Otero, M

2017-12-01

The biomass growth, pharmaceutical removal and light conversion efficiency of Chlorella sorokiniana under the presence of paracetamol (PC) and salicylic acid (SaC) were assessed and compared at two different concentrations of these pharmaceuticals (I: 25 mg l -1 , II: 250 mg l -1 ). Microalgae were resistant to these concentrations and, moreover, their growth was significantly stimulated (p ≤ 0.05) under these drugs (biomass concentration increased above 33% PCI, 35% SaCI, 13% PCII and 45% SaCII, as compared with the respective positive controls). At the steady state of the semicontinuous culture, C. sorokiniana showed removal efficiencies above 41% and 69% for PCI and PCII, respectively; and above 93% and 98% for SaCI and SaCII, respectively. Under an irradiance of 370 μE m -2  s -1 , higher quantum yields were reached by microalgae under the presence of drugs, either at dose I or II, than by the respective positive controls. These results point to C. sorokiniana as a robust strain for the bioremediation of paracetamol and salicylic acid concentrated wastewaters. Copyright © 2016 Elsevier Ltd. All rights reserved.

Lipid profile and atherogenic predictor indices of albino rabbits administered coconut water as antidote to paracetamol overdose

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Chidi Uzoma Igwe

2016-11-01

Full Text Available Objective: To investigate the effects of coconut water intake on lipid profile and atherogenic predictor indices of albino rabbits overdosed with paracetamol using standard methods. Methods: Thirty-five albino rabbits weighing between 800–1200 g and aged between 2 and 3 months, were divided into 7 groups (I–VII of 5 animals each. Groups I, II and III were orally administered distilled water (20 mL/kg body weight, coconut water (20 mL/kg body weight and paracetamol (1000 mg/kg body weight respectively, for 7 days. Groups IV and V were administered coconut water (20 mL/kg body weight and silymarin (35 mg/kg body weight, respectively, for 6 days, then paracetamol (1000 mg/kg body weight on the 7th day. Groups VI and VII were administered distilled water for 6 days, paracetamol on the 7th day, then coconut water and silymarin, respectively, after 3 h. Results: The results showed that paracetamol overdose significantly reduced (P < 0.05 the mean body weight of the animals, increased the concentrations of serum total cholesterol, triacylglycerol, very low density lipoprotein cholesterol, low density lipoprotein cholesterol and the atherogenic predictor indices but reduced the serum high density lipoprotein cholesterol concentration of the animals relative to the control. The observed changes in the lipid profile and atherogenic predictor indices were countered more by post- than pre-treatment with coconut water and silymarin. Conclusions: The results indicated that coconut water acted as an effective antidote to paracetamol overdose-induced lipid abnormality in animals.

Estimation of paracetamol in urine to assess the diurnal variation

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Mithun Chandro Bhowmik

2018-05-01

Full Text Available The aim of the present study was to evaluate the diurnal variation of the pharmacokinetics of paracetamol by estimating the urinary free paracetamol level after single oral administration of paracetamol (500 mg tablet to 24 healthy male volunteers (students of a Medical College. The volunteers were given paracetamol tablet at 0800, 1400 and 2000 hours in three different days (two weeks apart and the urine samples of the volunteers were collected at just before and four hours after paracetamol administration. The samples were analyzed for free paracetamol using HPLC. The mean age was 21.1 ± 1.3 years and the body weight was 63.9 ± 10.9 kg. Three peaks were detected in the HPLC and one of them was identified for free paracetamol (RT= 4.7 min. The urine volume was nearly similar in all three times. After administration at 0800 hour, total free paracetamol excretion was significantly more than at 1400 and 2000 hours (p<0.001. The present study indicates that the dose reduction of paracetamol is required at morning than the afternoon or evening dose. 

Radioimmunological method for determination of cortisol in saliva

International Nuclear Information System (INIS)

Maleeva, A.; Mileva, Zh.; Kekhajova, M.

1989-01-01

A method was developed for determination of cortisol in saliva after being previously extracted with dichlormethane. Cortisol concentration in saliva of 19 subjects was determined by this method. The saliva cortisol levels were compared with those of blood plasma. No statistically significant difference was found. The method finds acceptance primarily when frequent measurements of cortisol level are neccessary as a screening technique and when strongly abnormally high levels should be differentiated from the normal ones: in this latter case determination of plasma cortisol is mandatory. 5 tabs., 8 refs

Handheld Device Adapted to Smartphone Cameras for the Measurement of Sodium Ion Concentrations at Saliva-Relevant Levels via Fluorescence

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Michelle Lipowicz

2015-06-01

Full Text Available The use of saliva sampling as a minimally-invasive means for drug testing and monitoring physiology is a subject of great interest to researchers and clinicians. This study describes a new optical method based on non-axially symmetric focusing of light using an oblate spheroid sample chamber. The device is simple, lightweight, low cost and is easily attached to several different brands/models of smartphones (Apple, Samsung, HTC and Nokia for the measurement of sodium ion levels at physiologically-relevant saliva concentrations. The sample and fluorescent reagent solutions are placed in a specially-designed, lightweight device that excludes ambient light and concentrates 470-nm excitation light, from a low-power photodiode, within the sample through non-axially-symmetric refraction. The study found that smartphone cameras and post-image processing quantitated sodium ion concentration in water over the range of 0.5–10 mM, yielding best-fit regressions of the data that agree well with a data regression of microplate luminometer results. The data suggest that fluorescence can be used for the measurement of salivary sodium ion concentrations in low-resource or point-of-care settings. With further fluorescent assay testing, the device may find application in a variety of enzymatic or chemical assays.

Paracetamol (acetaminophen) administration during neonatal brain development affects cognitive function and alters its analgesic and anxiolytic response in adult male mice.

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Viberg, Henrik; Eriksson, Per; Gordh, Torsten; Fredriksson, Anders

2014-03-01

Paracetamol (acetaminophen) is one of the most commonly used drugs for the treatment of pain and fever in children, both at home and in the clinic, and is now also found in the environment. Paracetamol is known to act on the endocannabinoid system, involved in normal development of the brain. We examined if neonatal paracetamol exposure could affect the development of the brain, manifested as adult behavior and cognitive deficits, as well as changes in the response to paracetamol. Ten-day-old mice were administered a single dose of paracetamol (30 mg/kg body weight) or repeated doses of paracetamol (30 + 30 mg/kg body weight, 4h apart). Concentrations of paracetamol and brain-derived neurotrophic factor (BDNF) were measured in the neonatal brain, and behavioral testing was done when animals reached adulthood. This study shows that acute neonatal exposure to paracetamol (2 × 30 mg) results in altered locomotor activity on exposure to a novel home cage arena and a failure to acquire spatial learning in adulthood, without affecting thermal nociceptive responding or anxiety-related behavior. However, mice neonatally exposed to paracetamol (2 × 30 mg) fail to exhibit paracetamol-induced antinociceptive and anxiogenic-like behavior in adulthood. Behavioral alterations in adulthood may, in part, be due to paracetamol-induced changes in BDNF levels in key brain regions at a critical time during development. This indicates that exposure to and presence of paracetamol during a critical period of brain development can induce long-lasting effects on cognitive function and alter the adult response to paracetamol in mice.

Efficacy and pharmacokinetics of intravenous paracetamol in the critically ill patient

NARCIS (Netherlands)

Samson, A.D.; Hunfeld, N.G.; Touw, D.J.; Melief, P.H.

2009-01-01

Introduction: Paracetamol (PCM) is a drug with analgesic and antipyretic properties. Despite its frequent use, little is known about its efficacy and pharmacokinetics (PK) when intravenously administered in the critically ill patient. A previous study suggests that therapeutic concentrations are not

Interventions for paracetamol (acetaminophen) overdose.

Science.gov (United States)

Chiew, Angela L; Gluud, Christian; Brok, Jesper; Buckley, Nick A

2018-02-23

Paracetamol (acetaminophen) is the most widely used non-prescription analgesic in the world. Paracetamol is commonly taken in overdose either deliberately or unintentionally. In high-income countries, paracetamol toxicity is a common cause of acute liver injury. There are various interventions to treat paracetamol poisoning, depending on the clinical status of the person. These interventions include inhibiting the absorption of paracetamol from the gastrointestinal tract (decontamination), removal of paracetamol from the vascular system, and antidotes to prevent the formation of, or to detoxify, metabolites. To assess the benefits and harms of interventions for paracetamol overdosage irrespective of the cause of the overdose. We searched The Cochrane Hepato-Biliary Group Controlled Trials Register (January 2017), CENTRAL (2016, Issue 11), MEDLINE (1946 to January 2017), Embase (1974 to January 2017), and Science Citation Index Expanded (1900 to January 2017). We also searched the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov database (US National Institute of Health) for any ongoing or completed trials (January 2017). We examined the reference lists of relevant papers identified by the search and other published reviews. Randomised clinical trials assessing benefits and harms of interventions in people who have ingested a paracetamol overdose. The interventions could have been gastric lavage, ipecacuanha, or activated charcoal, or various extracorporeal treatments, or antidotes. The interventions could have been compared with placebo, no intervention, or to each other in differing regimens. Two review authors independently extracted data from the included trials. We used fixed-effect and random-effects Peto odds ratios (OR) with 95% confidence intervals (CI) for analysis of the review outcomes. We used the Cochrane 'Risk of bias' tool to assess the risks of bias (i.e. systematic errors leading to overestimation of

PANSAID - PAracetamol and NSAID in combination

DEFF Research Database (Denmark)

Thybo, Kasper Højgaard; Hägi-Pedersen, Daniel; Wetterslev, Jørn

2017-01-01

compared to monotherapy. The objective of this trial is to investigate the analgesic effects and safety of paracetamol and ibuprofen alone and in combination in different dosages after THA. METHODS: PANSAID is a placebo-controlled, parallel four-group, multicentre trial with centralised computer......-generated allocation sequence and allocation concealment and with varying block size and stratification by site. Blinding of assessor, investigator, caregivers, patients and statisticians. Patients are randomised to four groups: (A) paracetamol 1 g × 4 and ibuprofen 400 mg × 4, (B) paracetamol 1 g × 4 and placebo, (C......) placebo and ibuprofen 400 mg × 4 and (D) paracetamol 0.5 g × 4 and ibuprofen 200 mg. The two co-primary outcomes are 24-h consumption of morphine and number of patients with one or more serious adverse events within 90 days after surgery. Secondary outcomes are pain scores during mobilisation and at rest...

Simultaneous determination of paracetamol, 4-Aminophenol, 4-Chloroacetanilid, Benzyl alcohol,Benzaldehyde and EDTA by HPLC methodin paracetamol injection ampoule

OpenAIRE

Ali Merrikhi Khosroshahi; Fereydoon Aflaki; Nader Saemiyan; Assem Abdollahpour; Ramin Asgharian

2016-01-01

Paracetamol that is known as acetaminophen have the most consume as an analgesic and antipyretic drug in the world. That is formulated in single compound or mixture at many forms such as tablets, syrups, suspensions and drops. The last form is intravenous injections. Paracetamol derived from 4-minophenol which is synthesized by acylated the P-acetaminophenol and acetic anhydride. 4-aminophenol is the main impurity at manufacturing of paracetamol which could produce by hydrolysis during sto...

Changes in the Concentration of Ions in Saliva and Dental Plaque after Application of CPP-ACP with and without Fluoride among 6-9 Year Old Children

Directory of Open Access Journals (Sweden)

Poureslami H

2017-03-01

Full Text Available Statement of Problem: The casein phospho peptide-amorphous calcium phosphate with or without fluoride (CPP-ACPF and CPP-ACP respectively are of considerably new materials which are highly recommended for prevention of dental caries. However, there is a shortage in literature on how they affect the ion concentration of saliva or dental plaque. Objectives: The aim of this study was to evaluate the concentration of calcium, phosphate and fluoride in the plaque and saliva of children with Early Childhood Caries (ECC after applying the CPP-ACP paste in comparison with the use of CPP- ACPF paste. Materials and Methods: One ml of un-stimulated saliva of 25 preschool children was collected and then 1 mg of the plaque sample was collected from the buccal surfaces of the two first primary molars on the upper jaw. CPP-ACP as well as CPP- ACPF pastes were applied on the tooth surfaces in two separate steps. In steps, plaque and saliva sampling was performed after 60 minutes. The amount of calcium ions was measured by Atomic Absorption Device and the amount of phosphate and fluoride ions was measured by Ion Chromatography instrument. Data were analyzed using Repeated Measurements ANOVA at a p < 0.05 level of significance. Results: Application of both CPP-ACPF and CPP-ACP significantly increased the concentration of calcium, phosphate, and fluoride in both saliva and dental plaque. Moreover, significantly higher salivary fluoride concentration was seen after application of CPP-ACPF compared to CPP-ACP. No other significant difference was observed between these two materials. Conclusions: CPP-ACPF can be more useful than CPP-ACP in protecting the primary teeth against caries process, especially when there is poor hygiene.

Hyperamylasaemia and acute pancreatitis in paracetamol poisoning

DEFF Research Database (Denmark)

Schmidt, L E; Dalhoff, K

2004-01-01

BACKGROUND: Hyperamylasaemia and even acute pancreatitis have been reported in patients with paracetamol poisoning. AIMS: To describe the incidence, clinical characteristics, and prognostic implications of hyperamylasaemia in paracetamol poisoning. PATIENTS: Six hundred and two patients transferred...... to a specialized unit with severe paracetamol poisoning and 212 unselected patients admitted from the local region. METHODS: Retrospective study based on hospital charts. The optimum threshold of serum amylase to discriminate non-survivors was identified. RESULTS: An elevated serum amylase (>100 U/L) occurred...... in 28 of the unselected patients (13%), in 218 of the transferred patients (36%), and in 118 of 148 patients (80%) with fulminant hepatic failure. Only 33 cases of paracetamol-associated acute pancreatitis were diagnosed. A threshold serum amylase of 150 U/L to discriminate non-survivors had sensitivity...

PANSAID-PAracetamol and NSAID in combination

DEFF Research Database (Denmark)

Thybo, Kasper Højgaard; Jakobsen, Janus Christian; Hägi-Pedersen, Daniel

2017-01-01

BACKGROUND: Effective postoperative pain management is essential for the rehabilitation of the surgical patient. The PANSAID trial evaluates the analgesic effects and safety of the combination of paracetamol and ibuprofen. This paper describes in detail the statistical analysis plan for the primary...... publication to prevent outcome reporting bias and data-driven analysis results. METHODS/DESIGN: The PANSAID trial is a multicentre, randomised, controlled, parallel, four-group clinical trial comparing the beneficial and harmful effects of different doses and combinations of paracetamol and ibuprofen...... of paracetamol and ibuprofen used in a perioperative setting. TRIAL REGISTRATION: ClinicalTrials.org identifier: NCT02571361 . Registered on 7 October 2015....

Paracetamol decreases steady-state exposure to lamotrigine by induction of glucuronidation in healthy subjects

DEFF Research Database (Denmark)

Gastrup, Sandra; Stage, Tore Bjerregaard; Fruekilde, Palle Bach Nielsen

2016-01-01

AIM: Patients receiving lamotrigine therapy frequently use paracetamol concomitantly. While one study suggests a possible, clinically relevant drug-drug interaction, practical recommendations of the concomitant use are inconsistent. We performed a systematic pharmacokinetic study in healthy...... volunteers to quantify the effect of 4-day treatment of paracetamol on the metabolism of steady-state lamotrigine. METHODS: Twelve healthy, male volunteers participated in an open-label, sequential interaction study. Lamotrigine was titrated to steady state (100 mg daily) over 36 days, and blood and urine...... sampling was performed in a non-randomised order with and without paracetamol (1 g four times daily). The primary endpoint was change in steady-state area under the plasma concentration-time curve of lamotrigine. Secondary endpoints were changes in total apparent oral clearance, renal clearance...

Interventions for paracetamol (acetaminophen) overdoses. Protocol for a Cochrane Review

DEFF Research Database (Denmark)

Brok, J; Buckley, N; Gluud, C

2001-01-01

Poisoning with paracetamol (acetaminophen) is a common cause of hepatotoxicity in the Western World. Inhibition of absorption, removal from the vascular system, antidotes, and liver transplantation are interventions for paracetamol poisoning.......Poisoning with paracetamol (acetaminophen) is a common cause of hepatotoxicity in the Western World. Inhibition of absorption, removal from the vascular system, antidotes, and liver transplantation are interventions for paracetamol poisoning....

A graphene-based electrochemical sensor for sensitive detection of paracetamol

Energy Technology Data Exchange (ETDEWEB)

Kang, Xinhuang; Wang, Jun; Wu, Hong; Liu, Jun; Aksay, Ilhan A.; Lin, Yuehe

2010-05-15

An electrochemical sensor based on the electrocatalytic activity of functionalized graphene for sensitive detection of paracetamol is presented. The electrochemical behaviors of paracetamol on graphene-modified glassy carbon electrodes (GCEs) were investigated by cyclic voltammetry and square-wave voltammetry. The results showed that the graphene-modified electrode exhibited excellent electrocatalytic activity to paracetamol. A quasi-reversible redox process of paracetamol at the modified electrode was obtained, and the over-potential of paracetamol decreased significantly compared with that at the bare GCE. Such electrocatalytic behavior of graphene is attributed to its unique physical and chemical properties, e.g., subtle electronic characteristics, attractive π–π interaction, and strong adsorptive capability. The sensor shows great promise for simple, sensitive, and quantitative detection of paracetamol.

Interrupted time-series analysis of regulations to reduce paracetamol (acetaminophen poisoning.

Directory of Open Access Journals (Sweden)

Oliver W Morgan

2007-04-01

Full Text Available Paracetamol (acetaminophen poisoning is the leading cause of acute liver failure in Great Britain and the United States. Successful interventions to reduced harm from paracetamol poisoning are needed. To achieve this, the government of the United Kingdom introduced legislation in 1998 limiting the pack size of paracetamol sold in shops. Several studies have reported recent decreases in fatal poisonings involving paracetamol. We use interrupted time-series analysis to evaluate whether the recent fall in the number of paracetamol deaths is different to trends in fatal poisoning involving aspirin, paracetamol compounds, antidepressants, or nondrug poisoning suicide.We calculated directly age-standardised mortality rates for paracetamol poisoning in England and Wales from 1993 to 2004. We used an ordinary least-squares regression model divided into pre- and postintervention segments at 1999. The model included a term for autocorrelation within the time series. We tested for changes in the level and slope between the pre- and postintervention segments. To assess whether observed changes in the time series were unique to paracetamol, we compared against poisoning deaths involving compound paracetamol (not covered by the regulations, aspirin, antidepressants, and nonpoisoning suicide deaths. We did this comparison by calculating a ratio of each comparison series with paracetamol and applying a segmented regression model to the ratios. No change in the ratio level or slope indicated no difference compared to the control series. There were about 2,200 deaths involving paracetamol. The age-standardised mortality rate rose from 8.1 per million in 1993 to 8.8 per million in 1997, subsequently falling to about 5.3 per million in 2004. After the regulations were introduced, deaths dropped by 2.69 per million (p = 0.003. Trends in the age-standardised mortality rate for paracetamol compounds, aspirin, and antidepressants were broadly similar to paracetamol

Sunitinib DDI with paracetamol, diclofenac, mefenamic acid and ibuprofen shows sex-divergent effects on the tissue uptake and distribution pattern of sunitinib in mice.

Science.gov (United States)

Tan, Siok Yean; Wong, Mei Mei; Tiew, Angela Lu Wun; Choo, Yai Wen; Lim, Suat Hun; Ooi, Ing Hong; Modamio, Pilar; Fernández, Cecilia; Mariño, Eduardo L; Segarra, Ignacio

2016-10-01

Pharmacokinetic interaction of sunitinib with diclofenac, paracetamol, mefenamic acid and ibuprofen was evaluated due to their P450 mediated metabolism and OATP1B1, OATP1B3, ABCB1, ABCG2 transporters overlapping features. Male and female mice were administered 6 sunitinib doses (60 mg/kg) PO every 12 h and 30 min before the last dose were administered vehicle (control groups), 250 mg/kg paracetamol, 30 mg/kg diclofenac, 50 mg/kg mefenamic acid or 30 mg/kg ibuprofen (study groups), euthanized 6 h post last administration and sunitinib plasma, liver, kidney, brain concentrations analyzed. Ibuprofen halved sunitinib plasma concentration in female mice (p Diclofenac and paracetamol female mice showed 45 and 25 % higher plasma concentrations than male mice which were 27 % lower in mefenamic acid female mice. Paracetamol increased 2.2 (p diclofenac, paracetamol, mefenamic acid and ibuprofen (p diclofenac group in male mice (liver, brain) and female mice (liver, kidney). These results portray gender-based sunitinib pharmacokinetic differences and NSAIDs selective effects on male or female mice, with potential clinical translatability.

Overdosed prescription of paracetamol (acetaminophen) in a teaching hospital.

Science.gov (United States)

Charpiat, B; Henry, A; Leboucher, G; Tod, M; Allenet, B

2012-07-01

Paracetamol is the most commonly used analgesic and antipyretic. Reviews of hospital use of paracetamol are scarce. Little is known about the appropriateness of the dose of paracetamol prescribed for hospitalized adults. The aim of this study was to report on the nature and the frequency of the overdosed prescription of paracetamol observed in adult patients over a 4.5-year period in a teaching hospital. Prescription analysis by pharmacists was performed once a week in six medical and three surgical departments and daily in a post-emergency unit. In cases of prescription error, the pharmacist notified the physician through an electronic alert when a computerized prescription order entry system was available or otherwise by face-to-face discussion. For each drug-related problem detected, the pharmacists recorded relevant details in a database. From October 2006 to April 2011, 44,404 prescriptions were reviewed and 480 alerts related to the overdosed prescription of paracetamol were made (1% of analyzed prescriptions). The extent of errors of dosage was within the intervals [90-120 mg/kg/d] and greater than 120 mg/kg/d for 87 and 11 patients respectively, who were prescribed a single non-combination paracetamol containing product. Sixty alerts concerned co-prescription of at least two paracetamol containing products with similar frequency for computerized (1.4/1000) or handwritten (1.2/1000) prescriptions. Prescriptions of paracetamol for hospitalized adults frequently exceed the recommended dosage. These results highlight the need for increased awareness of unintentional paracetamol overdose and support the initiation of an educational program aimed at physicians and nurses. Copyright © 2012. Published by Elsevier Masson SAS.

Human Saliva Collection Devices for Proteomics: An Update

Directory of Open Access Journals (Sweden)

Zohaib Khurshid

2016-06-01

Full Text Available There has been a rapid growth in the interest and adaptation of saliva as a diagnostic specimen over the last decade, and in the last few years in particular, there have been major developments involving the application of saliva as a clinically relevant specimen. Saliva provides a “window” into the oral and systemic health of an individual, and like other bodily fluids, saliva can be analyzed and studied to diagnose diseases. With the advent of new, more sensitive technologies to detect smaller concentrations of analytes in saliva relative to blood levels, there have been a number of critical developments in the field that we will describe. In particular, recent advances in standardized saliva collection devices that were not available three to four years ago, have made it easy for safe, simple, and non-invasive collection of samples to be carried out from patients. With the availability of these new technologies, we believe that in the next decade salivary proteomics will make it possible to predict and diagnose oral as well as systemic diseases, cancer, and infectious diseases, among others. The aim of this article is to review recent developments and advances in the area of saliva specimen collection devices and applications that will advance the field of proteomics.

Intercalation of paracetamol into the hydrotalcite-like host

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Kovanda, František; Maryšková, Zuzana; Kovář, Petr

2011-12-01

Hydrotalcite-like compounds are often used as host structures for intercalation of various anionic species. The product intercalated with the nonionic, water-soluble pharmaceuticals paracetamol, N-(4-hydroxyphenyl)acetamide, was prepared by rehydration of the Mg-Al mixed oxide obtained by calcination of hydrotalcite-like precursor at 500 °C. The successful intercalation of paracetamol molecules into the interlayer space was confirmed by powder X-ray diffraction and infrared spectroscopy measurements. Molecular simulations showed that the phenolic hydroxyl groups of paracetamol interact with hydroxide sheets of the host via the hydroxyl groups of the positively charged sites of Al-containing octahedra; the interlayer water molecules are located mostly near the hydroxide sheets. The arrangement of paracetamol molecules in the interlayer is rather disordered and interactions between neighboring molecules cause their tilting towards the hydroxide sheets. Dissolution tests in various media showed slower release of paracetamol intercalated in the hydrotalcite-like host in comparison with tablets containing the powdered pharmaceuticals.

Missed paracetamol (acetaminophen) overdose due to confusion regarding drug names.

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Hewett, David G; Shields, Jennifer; Waring, W Stephen

2013-07-01

Immediate management of drug overdose relies upon the patient account of what was ingested and how much. Paracetamol (acetaminophen) is involved in around 40% of intentional overdose episodes, and remains the leading cause of acute liver failure in many countries including the United Kingdom. In recent years, consumers have had increasing access to medications supplied by international retailers via the internet, which may have different proprietary or generic names than in the country of purchase. We describe a patient that presented to hospital after intentional overdose involving 'acetaminophen' purchased via the internet. The patient had difficulty recalling the drug name, which was inadvertently attributed to 'Advil', a proprietary non-steroidal anti-inflammatory drug. The error was later recognised when the drug packaging became available, but the diagnosis of paracetamol overdose and initiation of acetylcysteine antidote were delayed. This case illustrates the benefit of routinely measuring paracetamol concentrations in all patients with suspected poisoning, although this is not universally accepted in practice. Moreover, it highlights the importance of the internet as a source of medications for intentional overdose, and emphasises the need for harmonisation of international drug names to improve patient safety.

Solubility and degradation of paracetamol in subcritical water

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Emire Zuhal

2017-01-01

Full Text Available In this study, solubility and degradation of paracetamol were examined using subcritical water. Effect of temperature and static time was investigated during solubility process in subcritical water at constant pressure (50 bar. Experimental results show that temperature and static time have crucial effect on the degradation and solubility rates. Maximum mole fraction for solubility of paracetamol was obtained at 403 K as (14.68 ± 0.74×103. Approximation model for solubility of paracetamol was proposed. O2 and H2O2 were used in degradation process of paracetamol. Maximum degradation rate was found as 68.66 ± 1.05 and 100 ± 0.00 % using O2 and H2O2, respectively.

Powder compression properties of paracetamol, paracetamol hydrochloride, paracetamol cocrystals and coformers.

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Persson, Ann-Sofie; Ahmed, Hamzah; Velaga, Sitaram; Alderborn, Göran

2018-03-31

The objective was to study the relationship between crystal structure, particle deformation properties and tablet-forming ability for the monoclinic form of paracetamol (PRA), two cocrystals and a salt crystal of PRA in addition to two coformers (oxalic acid and 4,4'-bipyridine). Thus, the structure - property - performance relationship was investigated. Analytical powder compression was used for determination of effective plasticity, as inferred from the Heckel yield pressure and the Frenning parameter, and the elastic deformation was determined from in-die tablet elastic recovery. plasticity could not be linked to the crystal lattice structure as crystals containing zig-zag layers displayed similar plasticity as cThe rystals containing slip planes. In addition, crystals containing slip-planes displayed both high and low plasticity. The mechanical properties could neither be linked to the tablet-forming ability as the tablet tensile strength, unexpectedly, displayed a tendency to reduce with increased plasticity stiffness. Furthermore, the elastic deformation could not explain the tablet forming ability. It was concluded that no relationship between structure - property - performance for paracetamol and its cocrystals and salt could be established. Thus, it was indicated that to establish such a relationship an improved knowledge of crystallographic structure and inter-particle bonding during compaction is needed. Copyright © 2018. Published by Elsevier Inc.

Metabolism by conjugation appears to confer resistance to paracetamol (acetaminophen) hepatotoxicity in the cynomolgus monkey.

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Yu, Hong; Barrass, Nigel; Gales, Sonya; Lenz, Eva; Parry, Tony; Powell, Helen; Thurman, Dale; Hutchison, Michael; Wilson, Ian D; Bi, Luke; Qiao, Junwen; Qin, Qiuping; Ren, Jin

2015-03-01

1. Paracetamol overdose remains the leading cause of acute liver failure in humans. This study was undertaken in cynomolgus monkeys to study the pharmacokinetics, metabolism and the potential for hepatotoxic insult from paracetamol administration as a possible model for human toxicity. 2. No adverse effects were observed for doses of up to 900 mg/kg/d for 14 d. Only minor sporadic increases in alanine aminotransferase, aspartate aminotransferase and glutamate dehydrogenase in a number of animals were observed, with no clear dose response. 3. Toxicokinetic analysis showed good plasma exposure, albeit with less than proportional rises in Cmax and AUC, with increasing dose. The Cmax values in monkey were up to 3.5 times those associated with human liver toxicity and the AUC approx. 1000 times those associated with liver enzyme changes in 31-44% of human subjects. 4. Metabolite profiling of urine by (1)H NMR spectroscopy revealed paracetamol and its glucuronide and sulphate metabolites. Glutathione-derived metabolites, e.g. the cysteinyl conjugate, were only present in very low concentrations whilst the mercapturate was not detected. 5. These in vivo observations demonstrated that the cynomolgus monkey is remarkably resistant to paracetamol-induced toxicity and a poor model for investigating paracetamol-related hepatotoxicity in humans.

Potential protective effect of honey against paracetamol-induced hepatotoxicity.

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Galal, Reem M; Zaki, Hala F; Seif El-Nasr, Mona M; Agha, Azza M

2012-11-01

Paracetamol overdose causes severe hepatotoxicity that leads to liver failure in both humans and experimental animals. The present study investigates the protective effect of honey against paracetamol-induced hepatotoxicity in Wistar albino rats. We have used silymarin as a standard reference hepatoprotective drug. Hepatoprotective activity was assessed by measuring biochemical parameters such as the liver function enzymes, serum alanine aminotransferase (ALT) and serum aspartate aminotransferase (AST). Equally, comparative effects of honey on oxidative stress biomarkers such as malondialdyhyde (MDA), reduced glutathione (GSH) and glutathione peroxidase (GPx) were also evaluated in the rat liver homogenates.  We estimated the effect of honey on serum levels and hepatic content of interleukin-1beta (IL-1β) because the initial event in paracetamol-induced hepatotoxicity has been shown to be a toxic-metabolic injury that leads to hepatocyte death, activation of the innate immune response and upregulation of inflammatory cytokines. Paracetamol caused marked liver damage as noted by significant increased activities of serum AST and ALT as well as the level of Il-1β. Paracetamol also resulted in a significant decrease in liver GSH content and GPx activity which paralleled an increase in Il-1β and MDA levels. Pretreatment with honey and silymarin prior to the administration of paracetamol significantly prevented the increase in the serum levels of hepatic enzyme markers, and reduced both oxidative stress and inflammatory cytokines. Histopathological evaluation of the livers also revealed that honey reduced the incidence of paracetamol-induced liver lesions. Honey can be used as an effective hepatoprotective agent against paracetamol-induced liver damage.

The effect of food and ice cream on the adsorption capacity of paracetamol to high surface activated charcoal

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Høgberg, Lotte Christine Groth; Angelo, Helle Riis; Christophersen, Anne Bolette

2003-01-01

, the reductions compared to control (Hoegberg et al. 2002) varied between 11% and 26%. Even though a reduction in drug adsorption to activated charcoal was observed when food mixture or ice cream was added, the remaining adsorption capacity of both types of activated charcoal theoretically was still able......The effect of added food mixture (as if food was present in the stomach of an intoxicated patient) or 4 different types of ice cream (added as a flavouring and lubricating agent) on the adsorption of paracetamol (acetaminophen) to 2 formulations of activated charcoal was determined in vitro......, and paracetamol were mixed with either food mixture or ice cream followed by one hr incubation. The maximum adsorption capacity of paracetamol to activated charcoal was calculated using Langmuirs adsorption isotherm. Paracetamol concentration was analyzed using high pressure liquid chromatography. In the presence...

Paracetamol-induced spindle disturbances in V79 cells with and without expression of human CYP1A2

DEFF Research Database (Denmark)

Jensen, K G; Poulsen, H E; Doehmer, J

1996-01-01

Spindle disturbing effects in terms of c-mitosis and cytotoxicity of paracetamol were investigated in two Chinese hamster V79 cell lines, one of which (V79MZh1A2) was transfected with human CYP1A2. This enzyme catalyses the oxidative formation of the reactive paracetamol metabolite, NAPQI, believed...... to initiate hepatoxicity by covalent binding to proteins after overdose. In the native V79 cell line paracetamol increased c-mitosis frequency in a concentration dependent manner from 8.7 + or - 3.5% (control) to 66 + or - 18% at 20 mM. A significant increase to 13.3 + or - 3.5% was first seen at 2.5 m......M in the native cell line (Pparacetamol. At 5 mM paracetamol the c-mitosis frequency was 14.4 + or - 5.0% and 19.0 + or - 3...

Anaphylaxis following intravenous paracetamol: the problem is the solution.

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Jain, S S; Green, S; Rose, M

2015-11-01

Paracetamol is a ubiquitous analgesic and antipyretic that is widely administered, including by anaesthetists. Immediate hypersensitivity reactions to intravenous paracetamol are particularly rare. We report two cases involving four separate episodes of anaphylaxis to intravenous paracetamol in different perioperative settings without a past history of intolerance to the oral form. The allergological investigations are described, during which it became evident that both patients were allergic to an excipient (mannitol) present in the formulation and that neither was allergic to the principal agent (paracetamol). The importance of referral and investigation of perioperative drug reactions is underscored by these two cases.

Saliva of obese patients – is it different?

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Katarzyna Choromańska

2015-01-01

Full Text Available Obesity is a major public health concern that increases the risk of cardiovascular disease, type 2 diabetes and cancer. The incidence of obesity has increased significantly in recent years, not only in adults, but also in adolescents and children. This is evidenced by rapidly developing bariatric surgery, the most effective method of treating morbid obesity. Obesity is a multifactorial disease, and its pathogenesis is not completely understood. Numerous studies have been performed to clarify pathogenetic mechanisms, based mostly on blood and sometimes urine samples. Saliva is easily accessible and can be obtained non-invasively. Our aim was to review studies performed on saliva obtained from obese subjects in order to answer the title question.Obese people have different composition of salivary bacteria. Changes in the concentration of sialic acid, phosphorus and peroxidase activity as well as a lower flow rate of stimulated whole saliva promote dental caries and periodontal disease. Concentrations of salivary uric acid, endocannabinoids and CRP are increased in obesity and may provide a useful index of cardiometabolic risk. Assessment of fasting salivary ghrelin might facilitate choosing the best type of bariatric surgery for a specific patient. A significant decrease in salivary cortisol in women with morbid obesity also seems interesting.There is sufficient evidence to state that the saliva of obese and lean subjects is different. Saliva as an easily accessible research material seems promising, as shown by the few studies performed so far.

Intravenous paracetamol overdose in a paediatric patient

NARCIS (Netherlands)

Broeks, Ilse J.; Van Roon, Eric N.; Van Pinxteren-Nagler, Evelyn; De Vries, Tjalling W.

2013-01-01

BACKGROUND: Paracetamol is a widely used drug in children. In therapeutic doses, paracetamol has an excellent safety profile. Since the introduction of the intravenous form in 2004, only three reports of accidental overdose in children have been published. The low number probably is due to

Intake of paracetamol and risk of asthma in adults

DEFF Research Database (Denmark)

Thomsen, Simon Francis; Kyvik, Kirsten Ohm; Skadhauge, Lars

2008-01-01

Intake of paracetamol has been associated with development of asthma. The aim of this study was to address a possible association between intake of paracetamol and risk of adult-onset asthma. Using a multidisciplinary postal questionnaire survey concerning health and lifestyle we prospectively...... studied 19,349 adult twins enrolled in the nationwide Danish Twin Registry. There was a higher prevalence of new-onset asthma in subjects who reported frequent intake of paracetamol at baseline compared with subjects without this determinant (12.0% vs. 4.3%), OR = 3.03 (1.51-6.11), p = 0.005. The result...... remained significant after adjusting for sex, age, smoking, BMI, hay fever, eczema, and intake of medications other than paracetamol, OR = 2.16 (1.03-4.53), p = 0.041. Frequent intake of paracetamol is an independent risk factor for adult-onset asthma....

Dielectric spectroscopy in aqueous solutions of paracetamol over the frequency range of 20 Hz to 2 MHz at 293.15 K temperature

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Pandit, T. R.; Rana, V. A.

2018-05-01

Frequency domain dielectric relaxation spectroscopy plays an important role in the study of pharmaceutical drug molecules. The complex relative dielectric permittivity ɛ*(ω) = ɛ' - j ɛ" of aqueous solutions of paracetamol in the frequency range of 20 Hz to 2 MHz at a temperature range of 293.15 K are measured with the help of Agilent precision LCR meter E4980A along with four terminal liquid test fixture Agilent 16452A. Data of complex relative permittivity are used to calculate loss tangent for all concentrations of paracetamol in distilled water. Electrode polarization relaxation time has been calculated for all solutions. Effect of variation of concentrations of paracetamol in distilled water on these dielectric parameters is discussed.

Effects of different tastants on parotid saliva flow and composition

NARCIS (Netherlands)

Neyraud, E.; Heinzerling, C.I.; Bult, J.H.F.; Mesmin, C.; Dransfield, E.

2009-01-01

Saliva from parotid glands plays a role in taste perception. Parotid saliva is also stimulated by tastants. The aim of this work is to investigate the effects of different tastants on the parotid salivary response in six subjects. Five tastants were given in different concentrations in solution and

Therapeutic drug monitoring of caffeine in preterm infants: Could saliva be an alternative to serum?

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Chaabane, Amel; Chioukh, Fatma Z; Chadli, Zohra; Ben Fredj, Nadia; Ben Ameur, Karim; Ben Hmida, Hayet; Boughattas, Naceur A; Monastiri, Kamel; Aouam, Karim

2017-12-01

Evaluate whether saliva could be a useful alternative to serum for routine therapeutic drug monitoring of caffeine in preterm infants using the enzyme multiplied immunoassay technique (EMIT) assay. We conducted a prospective study including preterm infants (less than 34 weeks' amenorrhea) admitted to the intensive care and neonatal medicine department. All infants received 5, 10, 15, 20 and 25mg/kg/day of citrate caffeine intravenously from the first to the fifth day of birth, respectively. For each patient, two concomitant blood and saliva samples corresponding to the trough concentrations were collected 24hours after each caffeine dose. The caffeine concentrations were determined using the EMIT ® 2000 caffeine assay. Thirteen preterm infants were included. The saliva and the serum caffeine concentration increased proportionally to the administered dose. Saliva and serum kinetics were comparable and the saliva caffeine concentrations were correlated to the serum ones (r 2 =0.76). Saliva caffeine monitoring by EMIT is a valid, useful and safe alternative to serum in preterm infants. Copyright © 2017 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

Determinação espectrofotométrica simultânea de paracetamol e ibuprofeno em formulações farmacêuticas usando calibração multivariada Simultaneous spectrophotometric determination of paracetamol and ibuprofen in pharmaceutical formulations by multivariate calibration

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Marcelo M. Sena

2007-02-01

Full Text Available A simple method was proposed for determination of paracetamol and ibuprofen in tablets, based on UV measurements and partial least squares. The procedure was performed at pH 10.5, in the concentration ranges 3.00-15.00 µg ml-1 (paracetamol and 2.40-12.00 µg ml-1 (ibuprofen. The model was able to predict paracetamol and ibuprofen in synthetic mixtures with root mean squares errors of prediction of 0.12 and 0.17 µg ml-1, respectively. Figures of merit (sensitivity, limit of detection and precision were also estimated. The results achieved for the determination of these drugs in pharmaceutical formulations were in agreement with label claims and verified by HPLC.

Paracetamol suppository induced allergic contact dermatitis

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Rangaraj Murugaiyan

2016-01-01

Full Text Available Paracetamol, a para-aminophenol derivative given systemically can produce allergic reactions and has been reported so far, but allergic reaction due to suppositories is very rare. A 4 month old male child brought by his mother with complaints of raised dark coloured skin lesions over the perianal region for the past 3 days. The child had history of (H/o of fever for 4 days back for which paracetamol suppository was prescribed following which the child developed the lesion over the perianal region On examination a well defined hyperpigmented plaque of size 5*3 cms extending from anal verge posteriorly and anteriorly upto the beginning of scrotum with lateral extensions from the centre to the gluteals. In our case, the paracetamol suppository used caused an allergic reaction which made the child very irritable and the child developed an allergic contact dermatitis in the site where the suppository was kept and the surrounding area. We report this case because paracetamol suppository as such without preservative causing allergic contact dermatitis has not been reported so far and the treating doctor should keep in mind such type of reactions that might occur when used.

Randomized, controlled, multicentre clinical trial of the antipyretic effect of intravenous paracetamol in patients admitted to hospital with infection.

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Tsaganos, Thomas; Tseti, Ioulia K; Tziolos, Nikolaos; Soumelas, Georgios-Stefanos; Koupetori, Marina; Pyrpasopoulou, Athina; Akinosoglou, Karolina; Gogos, Charalambos; Tsokos, Nikolaos; Karagiannis, Asterios; Sympardi, Styliani; Giamarellos-Bourboulis, Evangelos J

2017-04-01

No randomized study has been conducted to investigate the use of intravenous paracetamol (acetaminophen, APAP) for the management of fever due to infection. The present study evaluated a new ready-made infusion of paracetamol. Eighty patients with a body temperature onset ≥38.5°C in the previous 24 h due to infection were randomized to a single administration of placebo (n = 39) or 1 g paracetamol (n = 41), and their temperature was recorded at standard intervals. Rescue medication with 1 g paracetamol was allowed. Serum samples were collected for the measurement of APAP and its metabolites. The primary endpoint was defervescence, defined as a core temperature ≤37.1°C. During the first 6 h, defervescence was achieved in 15 (38.5%) patients treated with placebo compared with 33 (80.5%) patients treated with paracetamol 1 g (P paracetamol 1 g was 3 h. Rescue medication was given to 15 (38.5%) and five (12.2%) patients allocated to placebo and paracetamol, respectively (P = 0.007); nine (60.0%) and two (40.0%) of these patients, respectively, experienced defervescence. No further antipyretic medication was needed for patients becoming afebrile with rescue medication. Serum glucuronide-APAP concentrations were significantly greater in the serum of patients who did not experience defervescence with paracetamol. The efficacy of paracetamol was not affected by serum creatinine. No drug-related adverse events were reported. The 1 g paracetamol formulation has a rapid and sustainable antipyretic effect on fever due to infection. Its efficacy is dependent on hepatic metabolism. © 2016 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

Silymarin nanoparticle prevents paracetamol-induced hepatotoxicity

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Das S

2011-06-01

Full Text Available Suvadra Das, Partha Roy, Runa Ghosh Auddy, Arup MukherjeeDepartment of Chemical Technology, University of Calcutta, Kolkata, West Bengal, IndiaAbstract: Silymarin (Sm is a polyphenolic component extracted from Silybum marianum. It is an antioxidant, traditionally used as an immunostimulant, hepatoprotectant, and dietary supplement. Relatively recently, Sm has proved to be a valuable chemopreventive and a useful antineoplastic agent. Medical success for Sm is, however, constrained by very low aqueous solubility and associated biopharmaceutical limitations. Sm flavonolignans are also susceptible to ion-catalyzed degradation in the gut. Proven antihepatotoxic activity of Sm cannot therefore be fully exploited in acute chemical poisoning conditions like that in paracetamol overdose. Moreover, a synchronous delivery that is required for hepatic regeneration is difficult to achieve by itself. This work is meant to circumvent the inherent limitations of Sm through the use of nanotechnology. Sm nanoparticles (Smnps were prepared by nanoprecipitation in polyvinyl alcohol stabilized Eudragit RS100® polymer (Rohm Pharma GmbH, Darmstadt, Germany. Process parameter optimization provided 67.39% entrapment efficiency and a Gaussian particle distribution of average size 120.37 nm. Sm release from the nanoparticles was considerably sustained for all formulations. Smnps were strongly protective against hepatic damage when tested in a paracetamol overdose hepatotoxicity model. Nanoparticles recorded no animal death even when administered after an established paracetamol-induced hepatic necrosis. Preventing progress of paracetamol hepatic damage was traced for an efficient glutathione regeneration to a level of 11.3 µmol/g in hepatic tissue due to Smnps.Keywords: silymarin, paracetamol, nanoparticle, glutathione, mouse hepatotoxicity

Naproxen, paracetamol and pamabrom versus paracetamol, pyrilamine and pamabrom in primary dysmenorrhea: a randomized, double-blind clinical trial.

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Ortiz, Mario I; Murguía-Cánovas, Gabriela; Vargas-López, Laura C; Silva, Rodolfo; González-de la Parra, Mario

2016-10-24

Dysmenorrhea is caused by the discharge of prostaglandins into the uterine tissue; therefore, non-steroidal anti-inflammatory drugs (NSAIDs) are the established initial therapy for dysmenorrhea. Dysmenorrhea therapy may include the administration of drug monotherapy or combination therapy. However, clinical scientific evidence on the efficacy of medications with two or three drugs combined is scarce or nonexistent. To evaluate and compare the efficacy and safety of two oral fixed-dose combinations for the relief of the symptoms of primary dysmenorrhea among Mexican women. One of the combinations is widely used in Mexico (paracetamol, pyrilamine and pamabrom) and the selected comparison was a medication with naproxen sodium, paracetamol and pamabrom based on the pathophysiology of primary dysmenorrhea. This was a single-centre, double blind, experimental, parallel group, randomized trial. Female patients with primary dysmenorrhea, older than 17 years and with pain intensity greater than 45 mm on a visual analogue scale, were included. The patients were then randomized to receive tablets with naproxen sodium, paracetamol and pamabrom or tablets with paracetamol, pyrilamine and pamabrom for one menstrual cycle. Patient evaluations of symptomatology and pain intensity were recorded throughout one menstrual period. Descriptive and inferential statistical analyses were utilized. An intention-to-treat population of 91 women, with a mean age of 21.3 ± 3.2 years, received paracetamol, pyrilamine and pamabrom tablets, and 98 participants, with a mean age of 21.0 ± 3.2 years, received naproxen sodium, paracetamol and pamabrom tablets. The participants’ assessments of pain on the Visual Analogue Scale during the menstrual cycle demonstrated a significant reduction in both treatment groups (p0.05). The results showed that both drug combinations were not different in reducing dysmenorrheic pain. Likewise, both treatments were well tolerated. Therefore, both treatments may be

Concomitant overdosing of other drugs in patients with paracetamol poisoning

DEFF Research Database (Denmark)

Schmidt, Lars E; Dalhoff, Kim

2002-01-01

AIMS: Paracetamol is frequently involved in intended self-poisoning, and concomitant overdosing of other drugs is commonly reported. The purpose of the study was to investigate further concomitant drug overdose in patients with paracetamol poisoning and to evaluate its effects on the outcome...... of the paracetamol intoxication. METHODS: Six hundred and seventy-one consecutive patients admitted with paracetamol poisoning were studied and concomitant drug intake was recorded. The relative risk of hepatic encephalopathy, death or liver transplantation, hepatic dysfunction, liver cell damage, and renal...... favourable outcome was observed in patients with concomitant NSAID overdose. CONCLUSIONS: Concomitant overdosing of benzodiazepines or analgesics is frequent in patients admitted with paracetamol poisoning. Concomitant benzodiazepine or acetylsalicylic acid overdose was associated with more severe toxicity...

Effects of Methionine Containing Paracetamol Formulation on ...

African Journals Online (AJOL)

Effects of Methionine Containing Paracetamol Formulation on Serum Vitamins and Trace Elements in Male Rats. AA Iyanda, JI Anetor, DP Oparinde, FAA Adeniyi. Abstract. Methionine is an effective antidote in the treatment of paracetamol-induced toxicity but at large doses it has been reported to induce or aggravate a ...

Colorimetric determination of a paracetamole in raw material and in pharmaceutical dosage forms

International Nuclear Information System (INIS)

Usifoh, C.O; Adelusi, S.A.; Adebambo, R.F.

2002-01-01

A rapid, accurate and simple method is proposed for the determination of p-acetaminophen (paracetamole) in raw material, tablets and syrups. The method is based on measuring the intensity of the yellow color that developed when acute acetaminophen is allowed to react with p-dimethylaminobenzaldehyde in 2M HCl after heating. The color which absorbs in the visible region of gamma 450 nm is stable for several hours and the intensity is directly proportional to the concentration of the drug, that is, Beer lambert law is obeyed. The method can be used to analyse paracetamole in raw material and in pharmaceutical dosage forms. (author)

Simultaneous determination of paracetamol and penicillin V by square-wave voltammetry at a bare boron-doped diamond electrode

International Nuclear Information System (INIS)

Švorc, Ľubomír; Sochr, Jozef; Tomčík, Peter; Rievaj, Miroslav; Bustin, Dušan

2012-01-01

Highlights: ► Unmodified BDD electrode = sensitive electrochemical sensor for drugs determination. ► No special pretreatment of samples except simple dilution. ► Selective method, common compounds present in urine do not interfere in high excess. ► Simultaneous determination of PAR and PEN has yet not been published in literature. - Abstract: A simple, sensitive and selective square-wave voltammetry method for simultaneous determination of paracetamol and penicillin V on a bare (unmodified) boron-doped diamond electrode has been developed. The good potential separation of about 0.35 V between the oxidation peak potentials of both drugs present in mixture was found. It was found by cyclic voltammetry that paracetamol gave quasireversible wave and penicillin V provided irreversible oxidation peak. The effect of supporting electrolyte, pH and scan rate on voltammetric response of both drugs was studied to select the optimum experimental conditions. The optimal conditions for quantitative simultaneous determination were obtained in acetate buffer solution at pH 5.0. The oxidation peak of paracetamol and penicillin V showed a systematic increase in peak currents with increase of their concentration. The calibration curves for the simultaneous determination of paracetamol and penicillin V exhibited the good linear responses within the concentration range from 0.4 to 100 μM for both drugs. The detection limit was established to 0.21 and 0.32 μM for paracetamol and penicillin V, respectively. The method proved the good sensitivity, repeatability (RSD of 1.5 and 2.1% for mixture solution of 10 μM PCM and PEN) and selectivity when influence of interferents commonly existing in human urine was negligible. The practical analytical utility of proposed method was demonstrated by simultaneous determination of paracetamol and penicillin V in human urine samples, with results similar to those obtained using a high-performance liquid chromatography method as an

CHROMOGRANIN A DETECTION IN SALIVA OF TYPE 2 DIABETES PATIENTS

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Martine Soell

2010-02-01

Full Text Available Chromogranin A is present in secretion granules of nerve, endocrine and immune cells and is a precursor of several peptides with antibacterial and antifungal properties at micromolar concentrations.Our aim in this prospective, double blind study, was to determine the expression of chromogranin A and its peptides at protein level in saliva of type 2 diabetic patients and thereby to obtain a new non-invasive diagnostic means for the future.Saliva was taken from 30 type 2 diabetic patients and 30 healthy individuals at the same time interval in the morning without any oral stimuli. Circadianic periodics in protein productions have been avoided. The presence of chromogranin A and its derived peptides was determined in whole saliva, after centrifugation at 40C for 12 min at 14 000 rpm, by SDS-PAGE electrophoresis and Immunoblotting (Western Blot. To ensure same protein concentrations Bradford protein quantification assay has been performed before.For the first time, we have determined an overexpression of chromogranin A in saliva of diabetic patients in 100% of the individuals.Chromogranin A, a circulating biomarker for epithelial tumours, is also overexpressed in saliva of type 2 diabetic patients. To confirm our results, more studies with a large amount of patients is necessary.

Chromogranin A Detection in Saliva of Type 2 Diabetes Patients

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Martine Soell

2010-02-01

Full Text Available Chromogranin A is present in secretion granules of nerve, endocrine and immune cells and is a precursor of several peptides with antibacterial and antifungal properties at micromolar concentrations.Our aim in this prospective, double blind study, was to determine the expression of chromogranin A and its peptides at protein level in saliva of type 2 diabetic patients and thereby to obtain a new non-invasive diagnostic means for the future.Saliva was taken from 30 type 2 diabetic patients and 30 healthy individuals at the same time interval in the morning without any oral stimuli. Circadianic periodics in protein productions have been avoided. The presence of chromogranin A and its derived peptides was determined in whole saliva, after centrifugation at 4°C for 12 min at 14 000 rpm, by SDS-PAGE electrophoresis and Immunoblotting (Western Blot. To ensure same protein concentrations Bradford protein quantification assay has been performed before.For the first time, we have determined an overexpression of chromogranin A in saliva of diabetic patients in 100% of the individuals.Chromogranin A, a circulating biomarker for epithelial tumours, is also overexpressed in saliva of type 2 diabetic patients. To confirm our results, more studies with a large amount of patients is necessary.

Evaluation of Palm Oil-Based Paracetamol Suppositories by ...

African Journals Online (AJOL)

Methods: The suppository base was prepared by mixing hydrogenated palm oil and palm kernel ... DSC can be used to predict drug release in paracetamol suppository formulations. Keywords: Palm oil, Liquefaction time, Paracetamol, Suppositories, Thermal analysis. ..... Drug Evaluation & Research (CDER), Food and.

The impact of current tobacco use on the outcome of paracetamol poisoning

DEFF Research Database (Denmark)

Schmidt, L E; Dalhoff, K

2003-01-01

BACKGROUND: Tobacco smoke contains a number of substances that are capable of inducing cytochrome P450. Consequently, current tobacco use may enhance the hepatotoxicity from a paracetamol overdose by increasing the oxidative metabolism of paracetamol. AIM: To evaluate, by multivariate analysis......: Current tobacco use was very frequent in patients admitted with paracetamol poisoning. It was an independent risk factor of severe hepatotoxicity, acute liver failure and death following paracetamol overdose......., the effect of current tobacco use on the morbidity and mortality from paracetamol-induced hepatotoxicity. METHODS: A retrospective study was carried out on the basis of the hospital charts of 602 patients admitted with single-dose paracetamol poisoning for whom information on current tobacco use...

Some Biological Activities of Malaysian Leech Saliva Extract

OpenAIRE

Abdualrahman M. Abdualkader; Ahmed Merzouk; Abbas Mohammed Ghawi; and Mohammed Alaama

2011-01-01

Leeches were fed on the phagostimulatory solution through parafilm membrane. The satiated leeches were forced to regurgitate the solution by soaking them in an ice-container. The anticoagulant activity was ascertained using thrombin time assay (TT). The result revealed that the saliva concentration which increases TT by 100% (IC100) is 43.205µg/ml plasma. The antimicrobial activity of the saliva was tested against several bacterial spp. (E.coli, P.aeruginosa, B.cereus, Sal.typhi and S...

Total Protein of Whole Saliva as a Biomarker of Anaerobic Threshold

Science.gov (United States)

Bortolini, Miguel Junior Sordi; De Agostini, Guilherme Gularte; Reis, Ismair Teodoro; Lamounier, Romeu Paulo Martins Silva; Blumberg, Jeffrey B.; Espindola, Foued Salmen

2009-01-01

Saliva provides a convenient and noninvasive matrix for assessing specific physiological parameters, including some biomarkers of exercise. We investigated whether the total protein concentration of whole saliva (TPWS) would reflect the anaerobic threshold during an incremental exercise test. After a warm-up period, 13 nonsmoking men performed a…

Oral paracetamol (acetaminophen) for cancer pain.

Science.gov (United States)

Wiffen, Philip J; Derry, Sheena; Moore, R Andrew; McNicol, Ewan D; Bell, Rae F; Carr, Daniel B; McIntyre, Mairead; Wee, Bee

2017-07-12

Pain is a common symptom with cancer, and 30% to 50% of all people with cancer will experience moderate to severe pain that can have a major negative impact on their quality of life. Non-opioid drugs are commonly used to treat mild to moderate cancer pain, and are recommended for this purpose in the WHO cancer pain treatment ladder, either alone or in combination with opioids.A previous Cochrane review that examined the evidence for nonsteroidal anti-inflammatory drugs (NSAIDs) or paracetamol, alone or combined with opioids, for cancer pain was withdrawn in 2015 because it was out of date; the date of the last search was 2005. This review, and another on NSAIDs, updates the evidence. To assess the efficacy of oral paracetamol (acetaminophen) for cancer pain in adults and children, and the adverse events reported during its use in clinical trials. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase from inception to March 2017, together with reference lists of retrieved papers and reviews, and two online study registries. We included randomised, double-blind, studies of five days' duration or longer, comparing paracetamol alone with placebo, or paracetamol in combination with an opioid compared with the same dose of the opioid alone, for cancer pain of any intensity. Single-blind and open studies were also eligible for inclusion. The minimum study size was 25 participants per treatment arm at the initial randomisation. Two review authors independently searched for studies, extracted efficacy and adverse event data, and examined issues of study quality and potential bias. We did not carry out any pooled analyses. We assessed the quality of the evidence using GRADE and created a 'Summary of findings' table. Three studies in adults satisfied the inclusion criteria, lasting up to one week; 122 participants were randomised initially, and 95 completed treatment. We found no studies in children. One study was parallel-group, and

Long-term toxicological effects of paracetamol in rats

Directory of Open Access Journals (Sweden)

S.K. Majeed,

2013-06-01

Full Text Available The analgesic and antipyretic properties of paracetamol were first described in 1893, then it has been widely available as a non-prescription drug, with a therapeutic profile that reflects widespread safety and efficacy as well as paracetamol became the most widely used analgesic and antipyretic in children. It is the most frequently used over-the counter medicine in young children and is nearly universally used in infants. The drug is used by millions of children every day. The study was designed to study the toxicological effect of therapeutic dose of paracetamol after oral administration for three months in laboratory rats (Rattus norvegicous on the heart, kidney and liver. Results showed oral administration of the paracetamol for three months in laboratory rats showed that this drug has a severe damaging effect on most of the vital organs in the body like kidney, liver and heart.

Effects of saliva collection using cotton swab on cortisol enzyme immunoassay.

Science.gov (United States)

Kozaki, Tomoaki; Hashiguchi, Nobuko; Kaji, Yumi; Yasukouchi, Akira; Tochihara, Yutaka

2009-12-01

Cotton swabs are among the most commonly used devices for collecting saliva, but various studies have reported that their use impacts the results of salivary cortisol assays. These studies, however, estimated this impact by comparing the average of the concentration and/or scatter plots. In the present study, we estimated the impact of cotton swabs on the results of salivary cortisol enzyme immunoassay (EIA) by Bland-Altman plot. Eight healthy males (aged 20-23 years) provided four saliva samples on different days to yield a total of 32 samples. Saliva samples were collected directly in plastic tubes using plastic straws and then pipetted onto cotton swabs (cotton saliva collection) and into clear sterile tubes (passive saliva collection). There was a lower correlation between cotton and passive saliva collection. Individually, four subjects showed a negative correlation between passive and cotton saliva collection. A Bland-Altman plot indicated that cotton swabs causes a proportional bias on the EIA assay result. Our findings indicate a considerable effect of using cotton swabs for saliva collection, and subject-specific variability in the impact. A Bland-Altman plot further suggests possible reasons for this effect.

Effects of Paracetamol on NOS, COX, and CYP Activity and on Oxidative Stress in Healthy Male Subjects, Rat Hepatocytes, and Recombinant NOS

Science.gov (United States)

Trettin, Arne; Böhmer, Anke; Suchy, Maria-Theresia; Probst, Irmelin; Staerk, Ulrich; Stichtenoth, Dirk O.; Frölich, Jürgen C.

2014-01-01

Paracetamol (acetaminophen) is a widely used analgesic drug. It interacts with various enzyme families including cytochrome P450 (CYP), cyclooxygenase (COX), and nitric oxide synthase (NOS), and this interplay may produce reactive oxygen species (ROS). We investigated the effects of paracetamol on prostacyclin, thromboxane, nitric oxide (NO), and oxidative stress in four male subjects who received a single 3 g oral dose of paracetamol. Thromboxane and prostacyclin synthesis was assessed by measuring their major urinary metabolites 2,3-dinor-thromboxane B2 and 2,3-dinor-6-ketoprostaglandin F1α, respectively. Endothelial NO synthesis was assessed by measuring nitrite in plasma. Urinary 15(S)-8-iso-prostaglanding F2α was measured to assess oxidative stress. Plasma oleic acid oxide (cis-EpOA) was measured as a marker of cytochrome P450 activity. Upon paracetamol administration, prostacyclin synthesis was strongly inhibited, while NO synthesis increased and thromboxane synthesis remained almost unchanged. Paracetamol may shift the COX-dependent vasodilatation/vasoconstriction balance at the cost of vasodilatation. This effect may be antagonized by increasing endothelial NO synthesis. High-dosed paracetamol did not increase oxidative stress. At pharmacologically relevant concentrations, paracetamol did not affect NO synthesis/bioavailability by recombinant human endothelial NOS or inducible NOS in rat hepatocytes. We conclude that paracetamol does not increase oxidative stress in humans. PMID:24799980

Intentional and accidental paracetamol poisoning in childhood – a retrospective analysis

Directory of Open Access Journals (Sweden)

Katarzyna Kominek

2015-04-01

Full Text Available Paracetamol is one of the most commonly used analgesics and antipyretics available without limits as preparations of the OTC group (over the counter drugs. Overdose and poisoning with this drug always brings about the risk of acute hepatic failure. The objective of the study was a retrospective evaluation of patients hospitalized in the Paediatric Clinic during the period 2004–2012 due to poisoning with paracetamol.The analysis covered 44 patients hospitalized in the Paediatric Clinic during 2004–2012 due to poisoning with paracetamol. Patients were divided into three groups: intentional poisonings, accidental poisonings, and drug overdose.During the period of the study, 44 patients aged 2.1–17.1, poisoned with paracetamol, were hospitalized. Among these patients there were 30 (68.2% cases of intentional poisonings, 10 (22.7% of accidental poisonings, and only 4 patients (9.1% were children hospitalized after a paracetamol overdose. The majority of patients in all groups were females (93.3%.Paracetamol intoxication may occur after exceeding a single allowable dose, in the case of intentional poisoning, more rarely after exceeding the daily dose, in the case of intense pain complaints, or in the treatment of persistent fever.Based on the analysis performed, an increase was observed in the frequency of poisoning with paracetamol, especially intentional poisoning. Unlimited access to paracetamol as an OTC drug should be reconsidered.

Patients with the worst outcomes after paracetamol (acetaminophen)-induced liver failure have an early monocytopenia.

Science.gov (United States)

Moore, J K; MacKinnon, A C; Man, T Y; Manning, J R; Forbes, S J; Simpson, K J

2017-02-01

Acute liver failure (ALF) is associated with significant morbidity and mortality. Studies have implicated the immune response, especially monocyte/macrophages as being important in dictating outcome. To investigate changes in the circulating monocytes and other immune cells serially in patients with ALF, relate these with cytokine concentrations, monocyte gene expression and patient outcome. In a prospective case-control study in the Scottish Liver Transplant Unit, Royal Infirmary Edinburgh, 35 consecutive patients admitted with paracetamol-induced liver failure (POD-ALF), 10 patients with non-paracetamol causes of ALF and 16 controls were recruited. The peripheral blood monocyte phenotype was analysed by flow cytometry, circulating cytokines quantified by protein array and monocyte gene expression array performed and related to outcome. On admission, patients with worst outcomes after POD-ALF had a significant monocytopenia, characterised by reduced classical and expanded intermediate monocyte population. This was associated with reduced circulating lymphocytes and natural killer cells, peripheral cytokine patterns suggestive of a 'cytokine storm' and increased concentrations of cytokines associated with monocyte egress from the bone marrow. Gene expression array did not differentiate patient outcome. At day 4, there was no significant difference in monocyte, lymphocyte or natural killer cells between survivors and the patients with adverse outcomes. Severe paracetamol liver failure is associated with profound changes in the peripheral blood compartment, particularly in monocytes, related with worse outcomes. This is not seen in patients with non-paracetamol-induced liver failure. Significant monocytopenia on admission may allow earlier clarification of prognosis, and it highlights a potential target for therapeutic intervention. © 2016 John Wiley & Sons Ltd.

Therapeutic drug monitoring of nevirapine in saliva in Uganda using high performance liquid chromatography and a low cost thin-layer chromatography technique.

Science.gov (United States)

Lamorde, Mohammed; Fillekes, Quirine; Sigaloff, Kim; Kityo, Cissy; Buzibye, Allan; Kayiwa, Joshua; Merry, Concepta; Nakatudde-Katumba, Lillian; Burger, David; de Wit, Tobias F Rinke

2014-09-01

In resource limited settings access to laboratory monitoring of HIV treatment is limited and therapeutic drug monitoring is generally unavailable. This study aimed to evaluate nevirapine concentrations in saliva using low-cost thin-layer chromatography (TLC) and nevirapine concentrations in plasma and saliva using high performance liquid chromatography (HPLC) methods; and to correlate nevirapine plasma concentrations to HIV treatment outcomes in Ugandan patients. Paired plasma and stimulated saliva samples were obtained from Ugandan, HIV-infected adults on nevirapine-based ART. Nevirapine concentrations were measured using a validated HPLC method and a novel TLC method. Plasma nevirapine concentrations HPLC were considered subtherapeutic. Negative/positive predictive values of different thresholds for subtherapeutic nevirapine concentrations in saliva were determined. Virologic testing and, if applicable, HIV drug resistance testing was performed. Median (interquartile range, IQR) age of 297 patients was 39.1 (32.8-45.2) years. Three hundred saliva and 287 plasma samples were available for analysis. Attempts failed to determine nevirapine saliva concentrations by TLC. Using HPLC, median (IQR) nevirapine concentrations in saliva and plasma were 3.40 (2.59-4.47) mg/L and 6.17 (4.79-7.96) mg/L, respectively. The mean (coefficient of variation,%) nevirapine saliva/plasma ratio was 0.58 (62%). A cut-off value of 1.60 mg/L nevirapine in saliva was associated with a negative/positive predictive value of 0.99/0.72 and a sensitivity/specificity of 87%/98% for predicting subtherapeutic nevirapine plasma concentrations, respectively. Only 5% (15/287) of patients had subtherapeutic nevirapine plasma concentrations, of which 3 patients had viral load results > 400 copies/mL. Patients with nevirapine concentrations in plasma 400 copies/mL). The low-cost TLC technique for monitoring nevirapine in saliva was unsuccessful but monitoring nevirapine saliva and plasma

Anti-inflammatory and antinociceptive activities of Rhipicephalus microplus saliva

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D F Buccini

2018-01-01

Full Text Available Objective: To evaluate the antinociceptive and anti-inflammatory activities and the toxic effects of Rhipicephalus microplus saliva for elucidating the modulation mechanism between arthropod saliva and host. Methods: For saliva collection, engorged ticks were obtained from a controlled bovine infestation and collected by natural fall. The ticks were fixed and injected pilocarpine 0.2% for induction of salivation. Saliva was collected, lyophilized and stored at - 80 °C. Cytotoxic activity was assessed by the hemolysis method (25, 50, 100, 200 and 300 μ g/mL and MTT cell viability assay (2.5, 5, 10, 20 and 40 μ g/mL for 24, 48 and 72 h. Anti-inflammatory activity was evaluated using the method of neutrophil migration to the peritoneal cavity of mice at doses of 10, 15 and 20 mg/kg; antinociceptive activity was assessed using the acetic acid-induced writhing test, and formalin-induced paw-licking in mice at dose of 15 mg/kg. Results: Saliva did not cause erythrocytes hemolysis at any concentration tested, as well as did not decrease cell viability in the MTT assay. Saliva inhibited neutrophil migration by 87% and 73% at doses of 15 and 20 mg/kg, respectively. In the nociceptive tests, saliva presented analgesic activity of 69.96% in the abdominal writhing test, and of 84.41% in the formalin test. Conclusions: The study proves that Rhipicephalus microplus saliva has significant in vivo anti-inflammatory and antinociceptive activities. The data presented herein support the development of further studies to elucidate the active principles of Rhipicephalus microplus saliva and its mechanism of action and, in future, to develop novel anti-inflammatory and analgesic drugs.

The effect of regular medication on the outcome of paracetamol poisoning

DEFF Research Database (Denmark)

Schmidt, L E; Dalhoff, K

2002-01-01

BACKGROUND: Patients admitted with paracetamol overdose frequently receive one or more types of regular medication that may affect the outcome of the paracetamol intoxication. AIM: To describe the use of regular medication in patients with paracetamol poisoning and to evaluate its effects...... on morbidity and mortality. METHODS: Seven hundred and thirty-seven consecutive patients admitted with paracetamol poisoning were studied and the use of regular medication was recorded. The relative risk of hepatic encephalopathy, death or liver transplantation, severe hepatic dysfunction and severe...... hepatocellular injury was evaluated by multivariate analysis. RESULTS: Regular medication was received by 332 patients (45%). Medication with benzodiazepines (105 cases), antidepressants (100 cases), neuroleptics (75 cases), paracetamol (58 cases), oral contraceptives (51 cases), beta-agonists (40 cases), opioid...

Continuous analysis of parotid saliva during resting and short-duration simulated chewing

NARCIS (Netherlands)

Neyraud, E.; Bult, J.H.F.; Dransfield, E.

2009-01-01

Objective: Parotid saliva flow is increased by mastication and its composition is also modified. The aim of this work was to clarify the relationships between flow rate, pH and protein concentration, during resting and short-duration simulated chewing, using continuous and fractional saliva

Systemic exposure of Paracetamol (acetaminophen) was enhanced by quercetin and chrysin co-administration in Wistar rats and in vitro model: risk of liver toxicity.

Science.gov (United States)

Pingili, Ravindra Babu; Pawar, A Krishnamanjari; Challa, Siva R

2015-01-01

Intestinal P-glycoprotein (P-gp) and drug-metabolizing enzymes (DMEs) play an important role in the first-pass-metabolism (FPM) and pharmacokinetics (PK) of majority of drugs. Paracetamol is primarily metabolized by conjugation reactions and a little amount (∼15%) undergoes cytochrome P450 (CYP2E1)-mediated oxidative metabolism produces a hepatotoxic metabolite, N-acetyl-p-benzoquinonimine (NAPQI). Quercetin and chrysin are naturally occurring flavonoids, reported as modulators of P-gp and DMEs. Therefore, the objective of this study was to evaluate the effects of quercetin and chrysin on the pharmacokinetics of paracetamol using rats and non-everted gut sacs in vitro. Paracetamol was given orally (100 mg/kg) to rats alone and in combination with quercetin (5, 10 and 20 mg/kg) and chrysin (50, 100 and 200 mg/kg) once daily for 21 consecutive days. Blood samples were collected on the 1st day in single dose pharmacokinetic study (SDS) and on the 21st day in multiple pharmacokinetic studies (MDS). The plasma concentrations of paracetamol were determined by HPLC and PK parameters were calculated by using Kinetica (Version 5.1). The maximum plasma concentration (Cmax) and area under the curve (AUC0-12) of paracetamol was significantly increased by quercetin and chrysin co-administration in SDS and MDS. In non-everted rat gut sac method, the absorption of paracetamol was increased by presence of P-gp inhibitors (verapamil, quinidine and ketoconazole), quercetin and chrysin (50 μg/mL). Our findings suggested that the quercetin and chrysin might be inhibited the P-gp and metabolism of paracetamol; thereby increased the systemic exposure of paracetamol. Further studies are needed to evaluate whether the quercetin or chrysin are involved in the formation of NAPQI by CYP2E1 or not on isolated rat hepatocytes or using cell lines.

Parotid saliva composition during and after irradiation of head and neck cancer

International Nuclear Information System (INIS)

Funegaard, U.; Franzen, L.; Ericson, Th.; Henriksson, R.

1994-01-01

Parotid saliva composition was studied before, during and up to 18 months after the irradiation period in 16 cancer patients treated for malignancies in the head and neck region. Stimulated parotid saliva was collected prior to radiotherapy and, when possible, weekly during treatment. New samples were taken 2, 4, 6, 12 and 18 months after the end of radiotherapy. Nine of the 16 patients were treated with bilateral irradiation fields and 7 patients with unilateral irradiation fields, with a total dose not exceeding 52 Gy. During the entire irradiation period the fraction of glands producing measurable volumes of saliva decreased to 40%. In the post irradiation period the number of active glands gradually increased and saliva secretion rate returned to an average of 72% of the initial value 18 months after the end of irradiation. The concentrations of the measured variables increased already during the first week of radiotherapy and at the end of the treatment period the concentrations for total protein, salivary peroxidase, hexosamine and salivary IgA were significantly increased. The concentrations for total protein, salivary peroxidase and salivary IgA were still increased 6 months after the end of irradiation. At the 18-months observation all concentrations had returned to normal. (author)

Voltammetric sensing of paracetamole, dopamine and 4-aminophenol at a glassy carbon electrode coated with gold nanoparticles and an organophillic layered double hydroxide

International Nuclear Information System (INIS)

Yin, H.; Shang, K.; Meng, X.; Ai, S.

2011-01-01

A differential pulse voltammetric method was developed for the simultaneous determination of paracetamole, 4-aminophenol and dopamine at pH 7.0 using a glassy carbon electrode (GCE) coated with gold nanoparticles (AuNPs) and a layered double hydroxide sodium modified with dodecyl sulfate (SDS-LDH). The modified electrode displays excellent redox activity towards paracetamole, and the redox current is increased (and the corresponding over-potential decreased) compared to those of the bare GCE, the AuNPs-modified GCE, and the SDS-LDH-modified GCE. The modified electrode enables the determination of paracetamole in the concentration range from 0.5 to 400 μM, with a detection limit of 0.13 μM (at an S/N of 3). The sensor was successfully applied to the simultaneous determination of paracetamole and dopamine, and of paracetamole and 4-aminophenol, respectively, in pharmaceutical tablets and in spiked human serum samples. (author)

Single dose oral ibuprofen plus paracetamol (acetaminophen) for acute postoperative pain.

Science.gov (United States)

Derry, Christopher J; Derry, Sheena; Moore, R Andrew

2013-06-24

Combining two different analgesics in fixed doses in a single tablet can provide better pain relief than either drug alone in acute pain. This appears to be broadly true across a range of different drug combinations, in postoperative pain and migraine headache. Some combinations of ibuprofen and paracetamol are available for use without prescription in some acute pain situations. To assess the efficacy and adverse effects of single dose oral ibuprofen plus paracetamol for acute postoperative pain using methods that permit comparison with other analgesics evaluated in standardised trials using almost identical methods and outcomes. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library (Issue 4 of 12, 2013), MEDLINE (1950 to May 21st 2013), EMBASE (1974 to May 21st 2013), the Oxford Pain Database, ClinicalTrials.gov, and reference lists of articles. Randomised, double-blind clinical trials of single dose, oral ibuprofen plus paracetamol compared with placebo or the same dose of ibuprofen alone for acute postoperative pain in adults. Two review authors independently considered trials for inclusion in the review, assessed quality, and extracted data. We used validated equations to calculate the area under the pain relief versus time curve and derive the proportion of participants with at least 50% of maximum pain relief over six hours. We calculated relative risk (RR) and number needed to treat to benefit (NNT) for ibuprofen plus paracetamol, ibuprofen alone, or placebo. We used information on use of rescue medication to calculate the proportion of participants requiring rescue medication and the weighted mean of the median time to use. We also collected information on adverse events. Searches identified three studies involving 1647 participants. Each of them examined several dose combinations. Included studies provided data from 508 participants for the comparison of ibuprofen 200 mg + paracetamol 500 mg with placebo, 543

Radiolysis of paracetamol in dilute aqueous solution

International Nuclear Information System (INIS)

Szabó, László; Tóth, Tünde; Homlok, Renáta; Takács, Erzsébet; Wojnárovits, László

2012-01-01

Using radiolytic experiments hydroxyl radical (main reactant in advanced oxidation processes) was shown to effectively destroy paracetamol molecules. The basic reaction is attachment to the ring. The hydroxy-cyclohexadienyl radical produced in the further reactions may transform to hydroxylated paracetamol derivatives or to quinone type molecules and acetamide. The initial efficiency of aromatic ring destruction in the absence of dissolved O 2 is c.a. 10%. The efficiency is 2–3 times higher in the presence of O 2 due to its reaction with intermediate hydroxy-cyclohexadienyl radical and the subsequent ring destruction reactions through peroxi radical. Upon irradiation the toxicity of solutions at low doses increases with the dose and then at higher doses it decreases. This is due to formation of compounds with higher toxicity than paracetamol (e.g. acetamide, hidroquinone). These products, however, are highly sensitive to irradiation and degrade easily. - Highlights: ► Paracetamol is easily degraded in aqueous solution by low dose irradiation. ► Main degradation products are hydroxylated molecules, acetamide and hydroquinone. ► Toxicity of solutions goes through a maximum as a function of dose.

Radiolysis of paracetamol in dilute aqueous solution

Energy Technology Data Exchange (ETDEWEB)

Szabo, Laszlo [Institute of Isotopes, Hungarian Academy of Sciences, Budapest (Hungary); Budapest University of Technology and Economics, Budapest (Hungary); Toth, Tuende [Budapest University of Technology and Economics, Budapest (Hungary); Homlok, Renata [Institute of Isotopes, Hungarian Academy of Sciences, Budapest (Hungary); Takacs, Erzsebet [Institute of Isotopes, Hungarian Academy of Sciences, Budapest (Hungary); Wojnarovits, Laszlo [Institute of Isotopes, Hungarian Academy of Sciences, Budapest (Hungary)

2012-09-15

Using radiolytic experiments hydroxyl radical (main reactant in advanced oxidation processes) was shown to effectively destroy paracetamol molecules. The basic reaction is attachment to the ring. The hydroxy-cyclohexadienyl radical produced in the further reactions may transform to hydroxylated paracetamol derivatives or to quinone type molecules and acetamide. The initial efficiency of aromatic ring destruction in the absence of dissolved O{sub 2} is c.a. 10%. The efficiency is 2-3 times higher in the presence of O{sub 2} due to its reaction with intermediate hydroxy-cyclohexadienyl radical and the subsequent ring destruction reactions through peroxi radical. Upon irradiation the toxicity of solutions at low doses increases with the dose and then at higher doses it decreases. This is due to formation of compounds with higher toxicity than paracetamol (e.g. acetamide, hidroquinone). These products, however, are highly sensitive to irradiation and degrade easily. - Highlights: Black-Right-Pointing-Pointer Paracetamol is easily degraded in aqueous solution by low dose irradiation. Black-Right-Pointing-Pointer Main degradation products are hydroxylated molecules, acetamide and hydroquinone. Black-Right-Pointing-Pointer Toxicity of solutions goes through a maximum as a function of dose.

Effect of masticatory stimulation on the quantity and quality of saliva and the salivary metabolomic profile.

Directory of Open Access Journals (Sweden)

Nobuyuki Okuma

Full Text Available This study characterized the changes in quality and quantity of saliva, and changes in the salivary metabolomic profile, to understand the effects of masticatory stimulation.Stimulated and unstimulated saliva samples were collected from 55 subjects and salivary hydrophilic metabolites were comprehensively quantified using capillary electrophoresis-time-of-flight mass spectrometry.In total, 137 metabolites were identified and quantified. The concentrations of 44 metabolites in stimulated saliva were significantly higher than those in unstimulated saliva. Pathway analysis identified the upregulation of the urea cycle and synthesis and degradation pathways of glycine, serine, cysteine and threonine in stimulated saliva. A principal component analysis revealed that the effect of masticatory stimulation on salivary metabolomic profiles was less dependent on sample population sex, age, and smoking. The concentrations of only 1 metabolite in unstimulated saliva, and of 3 metabolites stimulated saliva, showed significant correlation with salivary secretion volume, indicating that the salivary metabolomic profile and salivary secretion volume were independent factors.Masticatory stimulation affected not only salivary secretion volume, but also metabolite concentration patterns. A low correlation between the secretion volume and these patterns supports the conclusion that the salivary metabolomic profile may be a new indicator to characterize masticatory stimulation.

Study of experiment on leaching of bisphenol A from infant books to artificial saliva.

Science.gov (United States)

Sajiki, Junko; Yanagibori, Ryoko; Kobayashi, Yaeko

2010-05-01

To assess the risk of bisphenol A (BPA) exposure when infants suck or chew infant books, the concentration of BPA leaching from infant books published by Japanese makers to artificial saliva was measured. The concentration of BPA leaching from 10 infant books to 15 ml artificial saliva or water was measured at 37 degrees C for 20 hrs. BPA concentration was measured by high-performance liquid chromatography-electrochemical detection (HPLC-ECD) with solid-phase extraction. BPA was leached from all books when pieces of them were dipped both into saliva and water for 20 hrs. The highest concentration of BPA leaching from one out of 10 books was 43.4 ng/ml (for 2 hrs) in saliva, which was estimated to be approximately 0.052 mg/kg body weight/day for infants aged 6-10 months. As BPA has endocrine-disrupting effects and poses higher risks in infants than in adults, it is desired to reduce BPA use in the printing of infant books from the viewpoint of child health.

Radioimmunological determination of chloramphenicol in the saliva of lactating cows

International Nuclear Information System (INIS)

Dotter, A.; Kroker, R.; Arnold, D.; Somogyi, A.

1987-01-01

In an effort to search for noninvasive methods suitable to monitor compliance with the ban of chloramphenicol (CAP) in milkproducing animals, the pharmacokinetic behavior of this drug in bovine saliva was investigated. As revealed by studies using a radioimmunological assay, CAP appears following its intracisternal (i.c.) or subcutaneous (s.c.) administration in the saliva of lactating cows. The level of sensitivity of the method (1.5 ng CAP per g saliva) was reached 14 and 18 days after i.c. and s.c. administration, respectively. At present, the question must remain open as to whether the concentration of CAP in the saliva can serve as a reliable indicator for the enforcement of the highest permissible level set at 1 ng CAP per g of milk by German regulations. (orig.) [de

Radioimmunological determination of chloramphenicol in the saliva of lactating cows

Energy Technology Data Exchange (ETDEWEB)

Dotter, A.; Kroker, R.; Arnold, D.; Somogyi, A.

1987-02-01

In an effort to search for noninvasive methods suitable to monitor compliance with the ban of chloramphenicol (CAP) in milk-producing animals, the pharmacokinetic behavior of this drug in bovine saliva was investigated. As revealed by studies using a radioimmunological assay, CAP appears following its intracisternal (i.c.) or subcutaneous (s.c.) administration in the saliva of lactating cows. The level of sensitivity of the method (1.5 ng CAP per g saliva) was reached 14 and 18 days after i.c. and s.c. administration, respectively. At present, the question must remain open as to whether the concentration of CAP in the saliva can serve as a reliable indicator for the enforcement of the highest permissible level set at 1 ng CAP per g of milk by German regulations.

Blood Contamination in Saliva: Impact on the Measurement of Salivary Oxidative Stress Markers

Directory of Open Access Journals (Sweden)

Natália Kamodyová

2015-01-01

Full Text Available Salivary oxidative stress markers represent a promising tool for monitoring of oral diseases. Saliva can often be contaminated by blood, especially in patients with periodontitis. The aim of our study was to examine the impact of blood contamination on the measurement of salivary oxidative stress markers. Saliva samples were collected from 10 healthy volunteers and were artificially contaminated with blood (final concentration 0.001–10%. Next, saliva was collected from 12 gingivitis and 10 control patients before and after dental hygiene treatment. Markers of oxidative stress were measured in all collected saliva samples. Advanced oxidation protein products (AOPP, advanced glycation end products (AGEs, and antioxidant status were changed in 1% blood-contaminated saliva. Salivary AOPP were increased in control and patients after dental treatment (by 45.7% and 34.1%, p<0.01. Salivary AGEs were decreased in patients after microinjury (by 69.3%, p<0.001. Salivary antioxidant status markers were decreased in both control and patients after dental treatment (p<0.05 and p<0.01. One % blood contamination biased concentrations of salivary oxidative stress markers. Saliva samples with 1% blood contamination are visibly discolored and can be excluded from analyses without any specific biochemic detection of blood constituents. Salivary markers of oxidative stress were significantly altered in blood-contaminated saliva in control and patients with gingivitis after dental hygiene treatment.

Paracetamol (acetaminophen): a blessing or a hidden curse?

Science.gov (United States)

Whitehouse, M W; Butters, D E

2014-02-01

This Journal has recently published a splendid review of all you need to know about paracetamol (Graham et al. 2013), an analgesic widely used in the long-term management of arthritis. It clearly presents the science and hard facts. This commentary, by contrast, discusses some aspects of the metapharmacology of paracetamol; particularly by asking questions of how we might extract more benefit and suffer less adverse reactions when using this analgesic in the context of non-transient inflammation. As both a drug and a toxin, paracetamol exemplifies how beneficial and/or deleterious responses may be conditioned by circumstances (disease stress, nutritional status, fasting, etc.).

Paracetamol (acetaminophen) for prevention or treatment of pain in newborns.

Science.gov (United States)

Ohlsson, Arne; Shah, Prakeshkumar S

2016-10-07

Newborn infants have the ability to experience pain. Hospitalised infants are exposed to numerous painful procedures. Healthy newborns are exposed to pain if the birth process consists of assisted vaginal birth by vacuum extraction or by forceps and during blood sampling for newborn screening tests. To determine the efficacy and safety of paracetamol for the prevention or treatment of procedural/postoperative pain or pain associated with clinical conditions in neonates. To review the effects of various doses and routes of administration (enteral, intravenous or rectal) of paracetamol for the prevention or treatment of pain in neonates. We used the standard search strategy of the Cochrane Neonatal Review group to search the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 4), MEDLINE via PubMed (1966 to 9 May 2016), Embase (1980 to 9 May 2016), and CINAHL (1982 to 9 May 2016). We searched clinical trials' databases, Google Scholar, conference proceedings, and the reference lists of retrieved articles. We included randomised and quasi-randomised controlled trials of paracetamol for the prevention/treatment of pain in neonates (≤ 28 days of age). Two review authors independently extracted data from the articles using pre-designed forms. We used this form to decide trial inclusion/exclusion, to extract data from eligible trials and to request additional published information from authors of the original reports. We entered and cross-checked data using RevMan 5 software. When noted, we resolved differences by mutual discussion and consensus. We used the GRADE approach to assess the quality of evidence. We included nine trials with low risk of bias, which assessed paracetamol for the treatment of pain in 728 infants. Painful procedures studied included heel lance, assisted vaginal birth, eye examination for retinopathy of prematurity assessment and postoperative care. Results of individual studies could not be combined in meta-analyses as the painful

Voluntary intake of paracetamol-enriched drinking water and its influence on the success of embryo transfer in mice.

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Fleischmann, Thea; Arras, Margarete; Sauer, Mareike; Saleh, Lanja; Rülicke, Thomas; Jirkof, Paulin

2017-04-01

Embryo transfer (ET) in mice is a key technique in biomedical research, and is carried out mostly via surgery by transferring founder embryos into pseudo-pregnant recipient females. To cover post-operative analgesic requirements in surrogate mothers, oral self-administration of painkillers has several advantages, but its effectiveness has also been criticized as voluntary ingestion of the drug can be uncertain. Additionally, concerns about potential negative side effects of analgesics on embryo viability and development have been raised. In this regard, we investigated the impact of orally administered analgesia by comparing the outcome of ET with and without paracetamol in the drinking water (3.5mg/ml) of surrogate mothers. Water intake increased significantly when paracetamol, as a sweet-tasting formulation (children's syrup), was added to the drinking water. Measurements of paracetamol concentrations in blood serum confirmed reasonable drug uptake. Success rate of ETs and the body weight of newborn offspring were not different whether paracetamol was administered for two days after surgery or not. In conclusion, paracetamol in drinking water was consumed voluntarily in substantial doses, without detectable side-effects, by freshly operated surrogate mothers, and can therefore be recommended as a feasible method for providing analgesic treatment for surgical ET in mice. Copyright © 2017 Elsevier Ltd. All rights reserved.

Paracetamol potentiates the antidepressant-like and anticompulsive-like effects of fluoxetine.

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Manna, Shyamshree S S; Umathe, Sudhir N

2015-04-01

Recent studies suggest the possible involvement of serotonergic and endocannabinoid systems in analgesic, anxiolytic, and anticonvulsant-like actions of paracetamol. Considering the fact that these systems play intricate roles in affective disorders, we investigated the effects of paracetamol in depression-like and compulsion-like behavior. Swiss mice (20-22 g) were subjected to forced swim, tail suspension, or marble-burying tests after an injection of paracetamol either alone or in the presence of AM251 (a CB1 antagonist), fenclonine (pCPA: a 5-HT synthesis inhibitor), AM404 (anandamide uptake inhibitor) or fluoxetine. Paracetamol dose dependently (50-400 mg/kg) decreased depressive and compulsive behaviors. These effects were comparable to those of fluoxetine (5, 10, or 20 mg/kg) and AM404 (10 or 20 mg/kg). Interestingly, fenclonine pretreatment completely abolished the effects of a 50 mg/kg dose of paracetamol. However, similar effects were not observed in AM251-pretreated mice at the same dose. In contrast, AM251 completely antagonized the effects of the 400 mg/kg dose, which was otherwise partially blocked in fenclonine-treated mice. Similar sets of results were observed with fluoxetine and AM404. Thus, it appears that paracetamol-induced antidepressant-like and anticompulsive effects may, at least partially, involve both the serotonergic and the endocannabinoid system. In addition, coadministration of paracetamol and fluoxetine/AM404 at subeffective doses produced synergistic effects, indicating that subthreshold doses of fluoxetine and paracetamol may enable better management in depression and obsessive-compulsive disorder comorbid patients.

Predicting outcome of paracetamol poisoning by using 14C-aminopyrine breath test

International Nuclear Information System (INIS)

Saunders, J.B.; Wright, N.; Lewis, K.O.

1980-01-01

The 14 C-aminopyrine ( 14 C-amidopyrine) breath test, carried out within 24 to 36 hours of an overdosage of paracetamol, was used to predict the extent of liver damage in 30 seriously poisoned patients. Mean 14 C0 2 excretion was 4.4% in 20 healthy control subjects; 5.5% in six patients who escaped injury; and 2.9%, 1.5%, and 0.2% in those with mild to moderate (12 patients), severe (eight patients), and fatal (four patients) liver damage respectively. This test proved to be a more reliable predictor of the extent of liver damage than plasma paracetamol concentration or half life or the results of conventional liver function tests and may enable treatment of hepatic failure to be started at an early stage. (author)

Prescription Use of Paracetamol and Risk for Ovarian Cancer in Denmark

DEFF Research Database (Denmark)

Baandrup, Louise; Friis, Søren; Dehlendorff, Christian

2014-01-01

It has been suggested that paracetamol reduces the risk for ovarian cancer. We examined the association between prescription use of paracetamol and ovarian cancer risk in a nationwide case-control study nested within the Danish female population. Case patients (n = 3471) were all women with a first......% confidence intervals (CIs) for ovarian cancer associated with use of paracetamol or nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs). All statistical tests were two-sided. Use of paracetamol was associated with a reduced odds ratio for ovarian cancer (OR = 0.82; 95% CI = 0.74 to 0.92; P ...) compared with nonuse, and the odds ratio decreased further with long-term (≥10 years), high-intensity paracetamol use (OR = 0.45; 95% CI = 0.24 to 0.86; P = .02). Use of nonaspirin NSAIDs was not associated with ovarian cancer risk....

Paracetamol removal in subsurface flow constructed wetlands

Science.gov (United States)

Ranieri, Ezio; Verlicchi, Paola; Young, Thomas M.

2011-07-01

SummaryIn this study two pilot scale Horizontal Subsurface Flow Constructed Wetlands (HSFCWs) near Lecce, Italy, planted with different macrophytes ( Phragmites australis and Typha latifolia) and an unplanted control were assessed for their effectiveness in removing paracetamol. Residence time distributions (RTDs) for the two beds indicated that the Typha bed was characterized by a void volume fraction (porosity) of 0.16 and exhibited more ideal plug flow behavior (Pe = 29.7) than the Phragmites bed (Pe = 26.7), which had similar porosity. The measured hydraulic residence times in the planted beds were 35.8 and 36.7 h when the flow was equal to 1 m 3/d. The Phragmites bed exhibited a range of paracetamol removals from 51.7% for a Hydraulic Loading Rate (HLR) of 240 mm/d to 87% with 120 mm/d HLR and 99.9% with 30 mm/d. The Typha bed showed a similar behavior with percentages of removal slightly lower, ranging from 46.7% (HLR of 240 mm/d) to >99.9% (hydraulic loading rate of 30 mm/d). At the same HLR values the unplanted bed removed between 51.3% and 97.6% of the paracetamol. In all three treatments the paracetamol removal was higher with flow of 1 m 3/d and an area of approx. 7.5 m 2 (half bed) than in the case of flow equal to 0.5 m 3/d with a surface treatment of approx. 3.75 m 2. A first order model for paracetamol removal was evaluated and half lives of 5.16 to 10.2 h were obtained.

Fourier Transform Infrared Spectroscopy and Photoacoustic Spectroscopy for Saliva Analysis.

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Mikkonen, Jopi J W; Raittila, Jussi; Rieppo, Lassi; Lappalainen, Reijo; Kullaa, Arja M; Myllymaa, Sami

2016-09-01

Saliva provides a valuable tool for assessing oral and systemic diseases, but concentrations of salivary components are very small, calling the need for precise analysis methods. In this work, Fourier transform infrared (FT-IR) spectroscopy using transmission and photoacoustic (PA) modes were compared for quantitative analysis of saliva. The performance of these techniques was compared with a calibration series. The linearity of spectrum output was verified by using albumin-thiocyanate (SCN(-)) solution at different SCN(-) concentrations. Saliva samples used as a comparison were obtained from healthy subjects. Saliva droplets of 15 µL were applied on the silicon sample substrate, 6 drops for each specimen, and dried at 37 ℃ overnight. The measurements were carried out using an FT-IR spectrometer in conjunction with an accessory unit for PA measurements. The findings with both transmission and PA modes mirror each other. The major bands presented were 1500-1750 cm(-1) for proteins and 1050-1200 cm(-1) for carbohydrates. In addition, the distinct spectral band at 2050 cm(-1) derives from SCN(-) anions, which is converted by salivary peroxidases to hypothiocyanate (OSCN(-)). The correlation between the spectroscopic data with SCN(-) concentration (r > 0.990 for transmission and r = 0.967 for PA mode) was found to be significant (P < 0.01), thus promising to be utilized in future applications. © The Author(s) 2016.

Quantitative study of non-stimulated human whole saliva using NAA

International Nuclear Information System (INIS)

Lewgoy, H.R.; Zamboni, C.B.; Sabrina Metairon; Medeiros, I.M.M.A.; Medeiros de, J.A.G.

2013-01-01

In the past few years, the use of saliva has increased as a method for diagnosis of a variety of diseases. Investigations of flow rates, pH, molecular components, hormones and proteins have presented significant progress in clinical testing as a diagnostic tool. Inorganic elements found in saliva also have important correlations that can assist in the diagnosis of periodontal disease, but these salivary components are still poorly investigated. In this study, we investigated non-stimulated whole saliva of 44 healthy subjects and 12 patients with periodontal disease, obtained from donors at Sao Paulo city (Brazil). Using neutron activation analysis (NAA) technique, we found considerable metabolic changes in the salivary composition of periodontal patients: abnormal concentrations of Br, Ca, I, K, Mg and S that may be associated with periodontal, with the most effective indicator of periodontal disease being Ca concentration. The data from healthy donors also provide a scientific basis for biomedical researches of other oral diseases. (author)

Determinação espectrofotométrica por injeção em fluxo de paracetamol (acetaminofeno em formulações farmacêuticas

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Aniceto Clezio

2002-01-01

Full Text Available A flow injection spectrophotometric procedure is proposed for the determination of paracetamol (acetaminophen in pharmaceutical formulations. Powdered and liquid samples were previously dissolved/diluted in 0.05 mol L-1 hydrochloric acid solution and a volume of 250 µL was injected directly into a carrier stream of this same acid solution, flowing at 2.5 mL min-1. Paracetamol reacts with sodium hypochlorite forming N-acetyl-p-benzoquinoneimine which then reacts with sodium salicylate in sodium hydroxide solution yielding a blue indophenol dye which was measured at 640 nm in the pH range of 9.5-10.0. Paracetamol was determined in pharmaceutical products in the 1.0 to 100.0 mg L-1 (3.3x10-6 a 6.6x10-4 mol L-1 concentration range, with a detection limit of 0.5 mg L-1 (1.6x10-6 mol L-1. The recovery of this analyte in five samples ranged from 98.0 to 103.6 %. The analytical frequency was 80 determinations per hour and the RSDs were less than 1% for paracetamol concentrations of 25.0, 50.0 and 75.0 mg L-1 (n=10. A paired t-test showed that all results obtained for paracetamol in commercial formulations using the proposed flow injection procedure and a spectrophotometric batch procedure agree at the 95% confidence level.

Prenatal Paracetamol Exposure and Wheezing in Childhood: Causation or Confounding?

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Enrica Migliore

Full Text Available Several studies have reported an increased risk of wheezing in the children of mothers who used paracetamol during pregnancy. We evaluated to what extent this association is explained by confounding.We investigated the association between maternal paracetamol use in the first and third trimester of pregnancy and ever wheezing or recurrent wheezing/asthma in infants in the NINFEA cohort study. Risks ratios (RR and 95% confidence intervals (CI were estimated after adjustment for confounders, including maternal infections and antibiotic use during pregnancy.The prevalence of maternal paracetamol use was 30.6% during the first and 36.7% during the third trimester of pregnancy. The prevalence of ever wheezing and recurrent wheezing/asthma was 16.9% and 5.6%, respectively. After full adjustment, the RR for ever wheezing decreased from 1.25 [1.07-1.47] to 1.10 [0.94-1.30] in the first, and from 1.26 [1.08-1.47] to 1.10 [0.93-1.29] in the third trimester. A similar pattern was observed for recurrent wheezing/asthma. Duration of maternal paracetamol use was not associated with either outcome. Further analyses on paracetamol use for three non-infectious disorders (sciatica, migraine, and headache revealed no increased risk of wheezing in children.The association between maternal paracetamol use during pregnancy and infant wheezing is mainly, if not completely explained by confounding.

The impact of current tobacco use on the outcome of paracetamol poisoning

DEFF Research Database (Denmark)

Schmidt, L E; Dalhoff, K

2003-01-01

BACKGROUND: Tobacco smoke contains a number of substances that are capable of inducing cytochrome P450. Consequently, current tobacco use may enhance the hepatotoxicity from a paracetamol overdose by increasing the oxidative metabolism of paracetamol. AIM: To evaluate, by multivariate analysis......, the effect of current tobacco use on the morbidity and mortality from paracetamol-induced hepatotoxicity. METHODS: A retrospective study was carried out on the basis of the hospital charts of 602 patients admitted with single-dose paracetamol poisoning for whom information on current tobacco use...... was available. RESULTS: In patients admitted with paracetamol poisoning, the rate of current daily tobacco use of 70% (424 of 602 patients) was considerably higher than the rate of 31% in the background population (chi-squared test: P

Eficacia de la asociación paracetamol-metamizol vs. paracetamol-dexketoprofeno en manejo de dolor agudo postoperatorio

OpenAIRE

García Ramiro, M.; Alonso Guardo, L.; Matilla Álvarez, A.; Bartol Sevillano, R.; Vaquero Roncero, L. M.; Muriel Villoria, C.

2013-01-01

Objetivo: El uso de fármacos con mecanismos diferentes combinados entre sí para el tratamiento del dolor, en concreto del dolor agudo postoperatorio, forma parte fundamental de un tipo de analgesia llamada multimodal. El objetivo de este trabajo es evaluar la eficacia de la asociación de paracetamol más metamizol y compararla con la asociación de paracetamol más dexketoprofeno en dolor agudo postoperatorio. Métodos: Diseñamos un estudio prospectivo de intervención en el que se incluyeron 42 p...

Pre-treatment by n-hexane extract of Phyllanthus niruri can alleviate paracetamol-induced damage of the rat liver

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Md Jalaluddin Iqbal

2007-03-01

Full Text Available The present study aimed to obtain and evaluate remedy against viral hepatitis with Phyllanthus niruri (Bhui amla. Viral infection and toxic doses of paracetamol produce similar pattern of hepatotoxicity. Hepatotoxicity was induced by administering paracetamol (750 mg/kg body weight, single dose intraperitoneal into one group (group P of rats. Propylene glycol (vehicle was administered (2 ml into another group (group V of rats. 4 groups of P. niruri extract-pretreated (200 mg/kg body weight/day for 7 days rats were administered the same single dose of paracetamol on the 7th day. Extract of P. niruri were obtained through ethanol (E, hexane (H, dichloromethane (D and butane (B. Rat groups were V, P, E + P, H + P, D + P and B + P. Each group consisted of 6 rats and were sacrificed on the 9th day. Parameters for evaluation were biochemical (serum ALT, serum AST, serum ALP, serum bilirubin, hepatic reduced glutathione concentrations and hepatic histology. Propylene glycol (group V appeared non-toxic to the liver while significant degrees of centrilobuler hepatotoxicity was observed in group P paracetamol-treated rats. The E + P group suggested significant improvements in the serum parameters but these parameters appeared better alleviated in the H + P group. Hepatic reduced glutathione concentrations were replenished to the control level in both E + P and H + P groups. Hepatic histology supported biochemical and other observations in the P, E + P and H + P groups. Lesser degrees of alleviations were observed in the D + P and B + P groups. However, the hexane extract-pretreated group (H + P appeared to provide the most significant hepatoprotection against paracetamol induced hepatotoxicity in the rat. Titration of the dose following isolation of the active ingredient might offer complete alleviation.

Pre-treatment by n-hexane extract of Phyllanthus niruri can alleviate paracetamol-induced damage of the rat liver

Directory of Open Access Journals (Sweden)

Md. Jalaluddin Iqbal, Fawzia Z. Dewan, S.A.R.Chowdhury, M.I.R. Mamun,

2007-06-01

Full Text Available The present study aimed to obtain and evaluate remedy against viral hepatitis with Phyllanthus niruri (Bhui amla. Viral infection and toxic doses of paracetamol produce similar pattern of hepatotoxicity. Hepatotoxicity was induced by administering paracetamol (750 mg/kg body weight, single dose intraperitoneal into one group (group P of rats. Propylene glycol (vehicle was administered (2 ml into another group (group V of rats. Four groups of P. niruri extract-pretreated (200 mg/kg body weight/day for 7 days rats were administered the same single dose of paracetamol on the 7th day. Extract of P. niruri were obtained through ethanol (E, hexane (H, dichloromethane (D and butane (B. Rat groups were V, P, E + P, H + P, D + P and B + P. Each group consisted of 6 rats and were sacrificed on the 9th day. Parameters for evaluation were biochemical (serum ALT, serum AST, serum ALP, serum bilirubin, hepatic reduced glutathione concentrations and hepatic histology. Propylene glycol (group V appeared non-toxic to the liver while significant degrees of centrilobuler hepatotoxicity was observed in group P paracetamol-treated rats. The E + P group suggested significant improvements in the serum parameters but these parameters appeared better alleviated in the H + P group. Hepatic reduced glutathione concentrations were replenished to the control level in both E + P and H + P groups. Hepatic histology supported biochemical and other observations in the P, E + P and H + P groups. Lesser degrees of alleviations were observed in the D + P and B + P groups. However, the hexane extract-pretreated group (H + P appeared to provide the most significant hepatoprotection against paracetamol induced hepatotoxicity in the rat. Titration of the dose following isolation of the active ingredient might offer complete alleviation.

Biochemical modifications of human whole saliva induced by pregnancy.

Science.gov (United States)

Salvolini, E; Di Giorgio, R; Curatola, A; Mazzanti, L; Fratto, G

1998-06-01

To assess human unstimulated whole saliva components during pregnancy, to determine the relation, if any, between pregnancy and oral health, particularly total protein concentration, alpha-amylase activity, sialic acid content and calcium and phosphate concentrations were evaluated. Cross-sectional study. Forty-five healthy primigravid women; 15 nonpregnant women acted as controls. 1. A higher total protein content at 10 and 21 weeks of gestation with respect to the controls and to pregnant women at 40 weeks; 2. a higher alpha-amylase activity at 10 and 21 weeks of gestation compared with the controls and to pregnant women at 40 weeks; 3. an increased sialic acid content at 21 and 40 weeks; 4. decreased calcium and phosphorus concentrations at 21 and 40 weeks of gestation. Pregnancy modifies saliva composition. This could play a pivotal role in the incidence of pregnancy-induced dental caries.

Suitability of saliva cortisol as a biomarker for hypothalamic-pituitary-adrenal axis activation assessment, effects of feeding actions, and immunostimulatory challenges in dairy cows

DEFF Research Database (Denmark)

Schwinn, A. -C.; Knight, C. H.; Bruckmaier, R. M.

2016-01-01

, current research focuses on noninvasive sampling of media other than blood, for example, saliva. The aim of this study was to assess the suitability of saliva cortisol as a biomarker under different physiological and immunological states in dairy cows. Our objectives were to 1) evaluate the relationship...... between HPA axis activation and saliva cortisol concentration, 2) investigate effects of some feeding action (as influenced by feed and water consumption) on saliva cortisol concentration, and 3) evaluate the time lag between plasma and saliva cortisol during induced inflammatory conditions...... administration. Saliva and blood samples were taken before, during, and after drinking, feeding, and ruminating. Only a low correlation between saliva and plasma cortisol concentrations (r = 0.03, P = 0.83) but no significant effects of the different feeding actions on saliva cortisol were observed. When...

The Effect of Preemptive Lornoxicam, Paracetamol and Paracetamol Lornoxicam Combinations on the Quality of Patient-Controlled Analgesia After Abdominal Surgery

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Aysenur Coskun

2013-10-01

Full Text Available Aim: We investigated total fentanyl dose, its side effects and the quality of Patient Controlled Analgesia (PCA using preemptive paracetamol, lornoxicam and their combination after abdominal surgery. Material and Method: After approval of the Hospital Ethic Committee of Atatürk University, Erzurum, Turkey, The study included 120 ASA I or II, patients aged between 18 to 70 years, scheduled to undergo elective abdominal surgery (midline incision surgery. Patients were randomly divided into four groups. In all cases, anesthesia was induced with 2mg/kg propofol and 0.6mg/kg rocuronium. Anesthesia was maintained by using 1-1.5% sevoflurane in 60% 40% nitrous oxide - O2. Group control (Group C, n=30: received intravenous (i.v. fentanyl through Patient Controlled Analgesia (PCA Group Lornoxicam (Group L, n=30: a one-time 8mg dose of i.v. lornoxicam was added, which was completed approximately 30 minutes before intubation.; Group paracetamol (Group P, n=30: received 1g i.v. paracetamol before intubation, followed by every 6 hours for a total of four times. Group lornoxicam and paracetamol (Group PL, n=30: received 8mg i.v. lornoxicam before intubation, and 1g i.v. paracetamol before intubation every 6 hours for a total of 4 times. During the postoperative 2, 4, 8, 12 and 24 hours, visual analogue scale (VAS, sedation, and nausea-vomiting scores, patient satisfaction, incidence of side effects and total amount of fentanyl used were recorded. Results: Total postoperative fentanyl consumption was significantly higher in GC than of the other groups. At 2, 8, 12, 24. hours, fentanyl consumption was found to be significantly lower in GL than that in GC. In GPL, fentanyl consumption was significantly lower than in GC at all time points. Discussion: We observed that preemptive 8 mg lornoxicam decreased PCA fentanyl consumption but a combination of lornoxicam and paracetamol was not superior to lornoxicam alone.

Detection of 70 kDa heat shock protein in the saliva of dairy cows.

Science.gov (United States)

Lamy, Elsa; Jurkovich, Viktor; Rodrigues, Lénia; Geraldo, Ana; Cachucho, Liliana; Silva, Flávio; Matos, Catarina; Capela E Silva, Fernando; Pinheiro, Cristina; Könyves, László; Bakony, Mikolt; Pereira, Alfredo

2017-08-01

This Research Communication describes, for the first time, the detection of HSP70 in saliva of dairy cows. Thermal stress is a major environmental stress that limits animal growth, metabolism, and productivity. The cellular response to heat stress involves the synthesis of heat shock proteins (HSPs), presumably to protect the functional stability of cells at increasing temperatures. HSP70 has been found to be present in cattle blood serum and may also be present in other secretory fluids, such as saliva, as already observed in humans. The aim of this study was to detect heat shock protein HSP70 in bovine saliva. Saliva samples were taken from higher- (n = 5) and lower milk producing (n = 5) Holstein-Friesian cows in summer and in winter for the detection of HSP70. HSP70 concentrations were assayed using the ELISA technique. Salivary HSP70 concentrations ranged from 0·524 to 12·174 ng/ml in cows. Higher salivary HSP70 concentrations were significantly associated with higher milk production and higher environmental temperature, but not with rectal temperature.

N-Acetyl-4-aminophenol (paracetamol), N-acetyl-2-aminophenol and acetanilide in urine samples from the general population, individuals exposed to aniline and paracetamol users.

Science.gov (United States)

Dierkes, Georg; Weiss, Tobias; Modick, Hendrik; Käfferlein, Heiko Udo; Brüning, Thomas; Koch, Holger M

2014-01-01

Epidemiological studies suggest associations between the use of N-acetyl-4-aminophenol (paracetamol) during pregnancy and increased risks of reproductive disorders in the male offspring. Previously we have reported a ubiquitous urinary excretion of N-acetyl-4-aminophenol in the general population. Possible sources are (1) direct intake of paracetamol through medication, (2) paracetamol residues in the food chain and (3) environmental exposure to aniline or related substances that are metabolized into N-acetyl-4-aminophenol. In order to elucidate the origins of the excretion of N-acetyl-4-aminophenol in urine and to contribute to the understanding of paracetamol and aniline metabolism in humans we developed a rapid, turbulent-flow HPLC-MS/MS method with isotope dilution for the simultaneous quantification of N-acetyl-4-aminophenol and two other aniline related metabolites, N-acetyl-2-aminophenol and acetanilide. We applied this method to three sets of urine samples: (1) individuals with no known exposure to aniline and also no recent paracetamol medication; (2) individuals after occupational exposure to aniline but no paracetamol medication and (3) paracetamol users. We confirmed the omnipresent excretion of N-acetyl-4-aminophenol. Additionally we revealed an omnipresent excretion of N-acetyl-2-aminophenol. In contrast, acetanilide was only found after occupational exposure to aniline, not in the general population or after paracetamol use. The results lead to four preliminary conclusions: (1) other sources than aniline seem to be responsible for the major part of urinary N-acetyl-4-aminophenol in the general population; (2) acetanilide is a metabolite of aniline in man and a valuable biomarker for aniline in occupational settings; (3) aniline baseline levels in the general population measured after chemical hydrolysis do not seem to originate from acetanilide and hence not from a direct exposure to aniline itself and (4) N-acetyl-2-aminophenol does not seem to be

Saliva Preservative for Diagnostic Purposes

Science.gov (United States)

Pierson, Duane L.; Mehta, Satish K.

2012-01-01

Saliva is an important body fluid for diagnostic purposes. Glycoproteins, glucose, steroids, DNA, and other molecules of diagnostic value are found in saliva. It is easier to collect as compared to blood or urine. Unfortunately, saliva also contains large numbers of bacteria that can release enzymes, which can degrade proteins and nucleic acids. These degradative enzymes destroy or reduce saliva s diagnostic value. This innovation describes the formulation of a chemical preservative that prevents microbial growth and inactivates the degradative enzymes. This extends the time that saliva can be stored or transported without losing its diagnostic value. Multiple samples of saliva can be collected if needed without causing discomfort to the subject and it does not require any special facilities to handle after it is collected.

Consumer concerns about paracetamol: a retrospective analysis of a medicines call centre.

Science.gov (United States)

Lau, Stephanie M; McGuire, Treasure M; van Driel, Mieke L

2016-06-08

To identify consumer information needs about paracetamol, the most commonly used analgesic and antipyretic worldwide. Retrospective analysis of medicines questions from the public. Australian consumer medicines call centre. Callers to National Prescribing Service Medicines Line between September 2002 and June 2010 (n=123 217). Enquiry profile: demographics, enquiry type and concurrent medicines included in paracetamol calls; question themes derived from subset of call narratives. Paracetamol comprised part of the enquiry in 5.2% of calls (n=6367). The caller age distribution for paracetamol calls was skewed towards a younger cohort, with 45.2% made by those aged 25-44 vs 37.5% in 'rest of calls'. Significantly more paracetamol-related calls were made for a child (23.7%) compared with 'rest of calls' (12.7%, pConsumers have many concerns about the use of paracetamol that may be under-recognised by healthcare providers, with the nature of enquiries differing across life stages. These concerns are not adequately addressed by available consumer information. Improving access to targeted information about paracetamol would promote the safe and effective use of this common medicine. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

The Relevancy of paracetamol and Breastfeeding Post Infant Vaccination: A Systematic Review

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Nurain Suleiman

2018-03-01

Full Text Available Background: Paracetamol may be used as an antipyretic agent for the treatment of fever, as well as an analgesic in the treatment of mild to moderate pain post-vaccination in infants. The use of paracetamol during fever may be or may not be recommended since it may alter the natural human body immune response, although it may reduce fever and fussiness. Objectives: The aims of this study are to describe the effectiveness of breastfeeding in reducing pain and paracetamol in reducing fever and pain post infant vaccination. Methods: Data sources and study selection was conducted by electronic searching of six databases. Manual reference checks of all articles on paracetamol and breastfeeding post infant vaccination published in the English language between 1978 and 2017. Two levels of screening were used on 9614 citations, which include screening of abstracts and titles followed by full text screening. The data synthesis were tabulated into study characteristics, quality, and effects. Results: Systematic review of breastfeeding included three studies from 9614 database searches found significant benefit from breastfeeding in pain scores and the duration of crying, as well as behavioural changes. None of the studies stated the detriment of breastfeeding before, during, and after immunization. Systematic review of paracetamol effectiveness included four studies from 1177 database searches found significant benefit from prophylaxis paracetamol in fever, one study found significant benefit from prophylaxis paracetamol in fussiness, and one study’s results were found to be not significant. Two studies on evaluating the safety of prophylactic paracetamol in 2009 found that antibody responses to several antigens were significantly reduced, and the other study in 1988 found that antibody titres to DTP bacteria of placebo and PCM did not differ significantly. Conclusions: The relevancy of giving paracetamol post all types of vaccination may be questionable

Radiolysis of paracetamol in dilute aqueous solution

Science.gov (United States)

Szabó, László; Tóth, Tünde; Homlok, Renáta; Takács, Erzsébet; Wojnárovits, László

2012-09-01

Using radiolytic experiments hydroxyl radical (main reactant in advanced oxidation processes) was shown to effectively destroy paracetamol molecules. The basic reaction is attachment to the ring. The hydroxy-cyclohexadienyl radical produced in the further reactions may transform to hydroxylated paracetamol derivatives or to quinone type molecules and acetamide. The initial efficiency of aromatic ring destruction in the absence of dissolved O2 is c.a. 10%. The efficiency is 2-3 times higher in the presence of O2 due to its reaction with intermediate hydroxy-cyclohexadienyl radical and the subsequent ring destruction reactions through peroxi radical. Upon irradiation the toxicity of solutions at low doses increases with the dose and then at higher doses it decreases. This is due to formation of compounds with higher toxicity than paracetamol (e.g. acetamide, hidroquinone). These products, however, are highly sensitive to irradiation and degrade easily.

SIMULTANEOUS DETERMINATION OF PARACETAMOL AND IBUPROFENE MIXTURES BY HIGH PERFORMANCE LIQUID CHROMATOGRAPHY

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Sophi Damayanti

2010-06-01

Full Text Available Analytical method for the determination of paracetamol and ibuprofene mixtures has been developed by High Performance Liquid Chromatography using C-18 column and acetinitrile - phosphate buffer pH = 4.5 (75:25 containing 0.075% sodium hexanesulfunate as a mobile phase. The detector was set at 215 nm. Using such conditions, retention time for paracetamol and ibuprofen was 4.89 and 7.11 min, respectively. The recovery for paracetamol and ibuprofen was found to be 101.07± 0.73% and 102.02 ± 1.58%, respectively. The detector limits of the method was 1.30 and 1.60 μg/mL with the relative standard deviation (RSD 0.74 and 1.52% for paracetamol and ibuprofen, respectively.   Keywords: paracetamol, ibuprofen, multi-component, validation, HPLC.

Study of the elemental composition of saliva of smokers and nonsmokers by X-ray fluorescence

International Nuclear Information System (INIS)

Poles, Antônio A.; Balcão, Victor M.; Chaud, Marco V.; Vila, Marta M.D.C.; Aranha, Norberto; Yoshida, Valquíria M.H.; Oliveira, José M.

2016-01-01

Cigarette smoking is a serious public health problem. According to data from the World Health Organization, it is estimated that currently more than 1.2 billion people worldwide do tobacco use and that smoking-related diseases are responsible for about 6 million deaths each. With attention to this, it is necessary to seek preventive and prognostic of trying to reduce these numbers and alert the public in general about the danger and the harm caused by its use. Thus, the objective of the research work undertaken was to evaluate and compare the chemical composition of collected saliva samples of smokers and nonsmokers by X-ray Fluorescence analyses. 32 individuals were selected, 16 of which used cigarette on a daily basis and the other 16 had never smoked. Saliva was collected with the help of a (sterile) disposable Pasteur pipette and samples sent to the Applied Nuclear Physics Laboratory at UNISO (LAFINAU), where analyzes were carried out. Individuals who agreed to participate in the study answered a questionnaire to define their profile of inclusion and signed an informed consent form (CEP Protocol no. 831.753 of 09/10/2014). The results clearly showed that there are differences in the concentrations of chemical elements in the saliva of smokers and non-smokers. The biggest discrepancies were found at concentrations of the chemical elements Sulfur, Phosphorus, Chlorine and Potassium, and smaller differences in the concentration of the elements Calcium, Manganese, Iron, Copper, Titanium, Vanadium and Nickel. In only one saliva sample, and in quite low amounts, arsenic was detected. The results indicate that smoking produces more significant changes in the saliva of women than in men, increasing the concentration of some elements in the saliva of female smokers, much more than in the male smokers. The cigarette usage time also appears to exert a greater influence on the composition of the saliva of women than in men, indicating that the damage caused by cigarette

Protein buffering in model systems and in whole human saliva.

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Andreas Lamanda

Full Text Available The aim of this study was to quantify the buffer attributes (value, power, range and optimum of two model systems for whole human resting saliva, the purified proteins from whole human resting saliva and single proteins. Two model systems, the first containing amyloglucosidase and lysozyme, and the second containing amyloglucosidase and alpha-amylase, were shown to provide, in combination with hydrogencarbonate and di-hydrogenphosphate, almost identical buffer attributes as whole human resting saliva. It was further demonstrated that changes in the protein concentration as small as 0.1% may change the buffer value of a buffer solution up to 15 times. Additionally, it was shown that there was a protein concentration change in the same range (0.16% between saliva samples collected at the time periods of 13:00 and others collected at 9:00 am and 17:00. The mode of the protein expression changed between these samples corresponded to the change in basic buffer power and the change of the buffer value at pH 6.7. Finally, SDS Page and Ruthenium II tris (bathophenantroline disulfonate staining unveiled a constant protein expression in all samples except for one 50 kDa protein band. As the change in the expression pattern of that 50 kDa protein band corresponded to the change in basic buffer power and the buffer value at pH 6.7, it was reasonable to conclude that this 50 kDa protein band may contain the protein(s belonging to the protein buffer system of human saliva.

Effects of isoflurane anesthesia and pilocarpine on rat parotid saliva flow

DEFF Research Database (Denmark)

Knudsen, Jacob Dronninglund; Nauntofte, Birgitte; Josipovic, M

2011-01-01

The purpose of this study was to investigate the effects of isoflurane on unstimulated and pilocarpine-stimulated parotid saliva secretion. Ten male Sprague-Dawley rats weighing 350-400 g were randomized into two groups, and the saliva flow rate and lag phase were measured at two doses of isoflur......The purpose of this study was to investigate the effects of isoflurane on unstimulated and pilocarpine-stimulated parotid saliva secretion. Ten male Sprague-Dawley rats weighing 350-400 g were randomized into two groups, and the saliva flow rate and lag phase were measured at two doses...... of isoflurane in a crossover study design. Increasing the isoflurane concentration from 1% to 2% was associated with a 19% decrease in saliva secretion rate, and the lag to saliva secretion was increased by 155%. To clarify whether the effect of isoflurane (1.5%) on the parotid flow varied with stimulus...... intensity, we measured the parotid flow induced by seven different doses of pilocarpine on sham-irradiated rats and rats irradiated with single doses of 15 Gy. A maximal pilocarpine response was obtained with 1.5 mg/kg in both irradiated and sham-irradiated rats; however, the parotid flow of the irradiated...

A sensitive electrochemical sensor for paracetamole based on a glassy carbon electrode modified with multiwalled carbon nanotubes and dopamine nanospheres functionalized with gold nanoparticles

International Nuclear Information System (INIS)

Liu, Xue; Wang, Ling-Ling; Wang, Ya-Ya; Zhang, Xiao-Yan

2014-01-01

We describe an electrochemical sensor for paracetamole that is based on a glassy carbon electrode modified with multiwalled carbon nanotubes and dopamine nanospheres functionalized with gold nanoparticles. The functionalized nanospheres were prepared by a chemical route and characterized by scanning electron microscopy. The well-dispersed gold nanoparticles were anchored on the dopamine nanosphere via a chemical reduction of the gold precursor. The stepwise fabrication of the modified electrode and its electrochemical response to paracetamole were evaluated using electrochemical impedance spectroscopy and cyclic voltammetry. The modified electrode displayed improved electrocatalytic activity towards paracetamole, a lower oxidation potential (371 mV), and a larger peak current when compared to a bare electrode or other modified electrodes. The kinetic parameters governing the electro-oxidation of paracetamole were studied, and the analytical conditions were optimized. The peak current was linearly related to the concentration of paracetamole in 0.8–400 μM range, and the detection limit was 50 nM (at an SNR of 3). The method was successfully applied to the determination of paracetamole in spiked human urine samples and gave recoveries between 95.3 and 105.2 %. (author)

PULMONARY AND LIVER DAMAGE DURING TREATMENT WITH ACETAMINOPHEN (PARACETAMOL

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L. I. Dvoretski

2016-01-01

Full Text Available This is a case report of pulmonary damage in the form of intestinal pneumonitis with severe respiratory failure during administration of acetaminophen (paracetamol. In addition, significant increase of ALT and AST levels without clinical signs of liver damage was observed in this patient. After glucocorticoids administration regression of radiological abnormal findings in the lungs along with normalization of liver enzymes values were registered. The rarity of interstitial pneumonitis induced by acetaminophen (paracetamol, especially in combination with liver damage, is emphasized. The presented patient history is the first case report of drug-induced hepatopulmonary syndrome during acetaminophen (paracetamol administration.

Comparison of analgesic efficacy of intravenous Paracetamol and intravenous dexketoprofen trometamol in multimodal analgesia after hysterectomy.

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Unal, Ciğdem; Cakan, Türkay; Baltaci, Bülent; Başar, Hülya

2013-10-01

[corrected] We aimed to evaluate analgesic efficacy, opioid-sparing, and opioid-related adverse effects of intravenous paracetamol and intravenous dexketoprofen trometamol in combination with iv morphine after total abdominal hysterectomy. Sixty American Society of Anesthesiologist Physical Status Classification I-II patients scheduled for total abdominal hysterectomy were enrolled to this double-blinded, randomized, placebo controlled, and prospective study. Patients were divided into three groups as paracetamol, dexketoprofen trometamol, and placebo (0.9% NaCl) due to their post-operative analgesic usage. Intravenous patient controlled analgesia morphine was used as a rescue analgesic in all groups. Pain scores, hemodynamic parameters, morphine consumption, patient satisfaction, and side-effects were evaluated. Visual Analog Scale (VAS) scores were not statistically significantly different among the groups in all evaluation times, but decrease in VAS scores was statistically significant after the evaluation at 12(th) h in all groups. Total morphine consumption (morphine concentration = 0.2 mg/ml) in group paracetamol (72.3 ± 38.0 ml) and dexketoprofen trometamol (69.3 ± 24.1 ml) was significantly lower than group placebo (129.3 ± 22.6 ml) (P dexketoprofen trometamol after surgery and the increase in global satisfaction score was significant only in group placebo. Dexketoprofen trometamol and Paracetamol didn't cause significant change on pain scores, but increased patients' comfort. Although total morphine consumption was significantly decreased by both drugs, the incidence of nausea and vomiting were similar among the groups. According to results of the present study routine addition of dexketoprofen trometamol and paracetamol to patient controlled analgesia morphine after hysterectomies is not recommended.

What do we (not) know about how paracetamol (acetaminophen) works?

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Toussaint, K; Yang, X C; Zielinski, M A; Reigle, K L; Sacavage, S D; Nagar, S; Raffa, R B

2010-12-01

Although paracetamol (acetaminophen), N-(4-Hydroxyphenyl)acetamide, is one of the world's most widely used analgesics, the mechanism by which it produces its analgesic effect is largely unknown. This lack is relevant because: (i) optimal pain treatment matches the analgesic mechanism to the (patho)physiology of the pain and (ii) modern drug discovery relies on an appropriate screening assay. To review the clinical profile and preclinical studies of paracetamol as means of gaining insight into its mechanism of analgesic action. A literature search was conducted of clinical and preclinical literature and the information obtained was organized and reviewed from the perspective of its contribution to an understanding of the mechanism of analgesic action of paracetamol. Paracetamol's broad spectrum of analgesic and other pharmacological actions is presented, along with its multiple postulated mechanism(s) of action. No one mechanism has been definitively shown to account for its analgesic activity. Further research is needed to uncover the mechanism of analgesic action of paracetamol. The lack of this knowledge affects optimal clinical use and impedes drug discovery efforts. © 2010 The Authors. JCPT © 2010 Blackwell Publishing Ltd.

Target biomarker profile for the clinical management of paracetamol overdose

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Vliegenthart, A D Bastiaan; Antoine, Daniel J; Dear, James W

2015-01-01

Paracetamol (acetaminophen) overdose is one of the most common causes of acute liver injury in the Western world. To improve patient care and reduce pressure on already stretched health care providers new biomarkers are needed that identify or exclude liver injury soon after an overdose of paracetamol is ingested. This review highlights the current state of paracetamol poisoning management and how novel biomarkers could improve patient care and save healthcare providers money. Based on the widely used concept of defining a target product profile, a target biomarker profile is proposed that identifies desirable and acceptable key properties for a biomarker in development to enable the improved treatment of this patient population. The current biomarker candidates, with improved hepatic specificity and based on the fundamental mechanistic basis of paracetamol-induced liver injury, are reviewed and their performance compared with our target profile. PMID:26076366

Saliva and wound healing.

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Brand, Henk S; Ligtenberg, Antoon J M; Veerman, Enno C I

2014-01-01

Oral wounds heal faster and with less scar formation than skin wounds. One of the key factors involved is saliva, which promotes wound healing in several ways. Saliva creates a humid environment, thus improving the survival and functioning of inflammatory cells that are crucial for wound healing. In addition, saliva contains several proteins which play a role in the different stages of wound healing. Saliva contains substantial amounts of tissue factor, which dramatically accelerates blood clotting. Subsequently, epidermal growth factor in saliva promotes the proliferation of epithelial cells. Secretory leucocyte protease inhibitor inhibits the tissue-degrading activity of enzymes like elastase and trypsin. Absence of this protease inhibitor delays oral wound healing. Salivary histatins in vitro promote wound closure by enhancing cell spreading and cell migration, but do not stimulate cell proliferation. A synthetic cyclic variant of histatin exhibits a 1,000-fold higher activity than linear histatin, which makes this cyclic variant a promising agent for the development of a new wound healing medication. Conclusively, recognition of the many roles salivary proteins play in wound healing makes saliva a promising source for the development of new drugs involved in tissue regeneration.

Levels of saliva cotinine in electronic cigarette users.

Science.gov (United States)

Etter, Jean-François

2014-05-01

To assess saliva cotinine levels in experienced users of e-cigarettes ('vapers'). An internet survey in 2011 and 2012, with collection of saliva vials by mail. Participants were 71 users of e-cigarettes enrolled mainly on websites and online forums dedicated to e-cigarettes. Use of e-cigarettes, tobacco and nicotine medications. Collection of saliva by mail and analysis of cotinine by liquid chromatography-mass spectrometry. Most participants (89%) were former smokers, most (92%) were using e-cigarettes daily, had been using e-cigarettes for 12 months on average and puffed a median of 150 times per day on their e-cigarettes [mean = 220 puffs/day, 95% confidence interval (CI) = 169-271]. The median concentration of nicotine in refill liquids was 16 mg/ml (mean = 16.4, 95% CI = 14.5-18.3). In the 62 e-cigarette users who, in the past 5 days, had not used any tobacco or nicotine medications, the median cotinine level was 353 ng/ml (mean = 374, 95% CI = 318-429), the correlation between cotinine and nicotine concentration in e-liquids was r = 0.33 (P = 0.013), and the correlation between cotinine and the number of cigarettes smoked per day before quitting smoking was r = 0.48 (P Addiction.

The effect of regular medication on the outcome of paracetamol poisoning

DEFF Research Database (Denmark)

Schmidt, L E; Dalhoff, K

2002-01-01

hepatocellular injury was evaluated by multivariate analysis. RESULTS: Regular medication was received by 332 patients (45%). Medication with benzodiazepines (105 cases), antidepressants (100 cases), neuroleptics (75 cases), paracetamol (58 cases), oral contraceptives (51 cases), beta-agonists (40 cases), opioid......, neuroleptics, paracetamol, oral contraceptives, beta-agonists or anticonvulsants in the multivariate analysis. CONCLUSIONS: Regular medication with psychotropic medication, analgesics, oral contraceptives, beta-agonists or anticonvulsants was frequent in patients admitted with paracetamol poisoning. Medication...

Passive exposure to tobacco smoke: saliva cotinine concentrations in a representative population sample of non-smoking schoolchildren

Energy Technology Data Exchange (ETDEWEB)

Jarvis, M J; Russell, M A; Feyerabend, C; Eiser, J R; Morgan, M; Gammage, P; Gray, E M

1985-10-05

Saliva cotinine concentrations in 569 non-smoking schoolchildren were strongly related to the smoking habits of their parents. When neither parent smoked the mean concentration was 0.44 ng/ml, rising to 3.38 ng/ml when both parents were cigarette smokers. Mothers smoking had a stronger influence than did fathers (p less than 0.01). In addition, there was a small independent effect of number of siblings who smoked (p less than 0.01). The dose of nicotine received from fathers smoking was estimated as equivalent to the active smoking of 30 cigarettes a year, that from mothers smoking as equivalent to smoking 50 cigarettes a year, and that from both parents smoking as equivalent to smoking 80 cigarettes a year. This unsolicited burden may be prolonged throughout childhood and poses a definite risk to health.

Overdosed paracetamol (acetaminophen) prescriptions and subsequent pharmacist interventions in French hospitals.

Science.gov (United States)

Charpiat, B; Bedouch, P; Rose, F X; Juste, M; Roubille, R; Conort, O; Allenet, B

2013-11-01

Little is known about the manner in which hospital pharmacists intervene for overdosed paracetamol prescriptions. The aim of this retrospective study was to describe the number and nature of pharmacists' interventions (PIs) for overdosed paracetamol adult prescriptions in hospitals. We studied PIs that had been documented by pharmacists on the French Society of Clinical Pharmacy website tool between 2007 and 2010. We identified PIs that were related to paracetamol-containing prescriptions of one brand name only (type 1) particularly for patients with body weight ≤ 50 kg who were prescribed 4 g/day, and PIs that concerned the co-prescription of two paracetamol-containing products (type 2). Among 60 hospitals, seven did not report any paracetamol overdose-related PIs. Of the 53 hospitals that had at least one PI, 16 did not report any type 1 PIs. Bodyweight, liver disease, cirrhosis and chronic alcoholism were absent recorded criterion by most of the hospitals included in this study. Previously published studies have highlighted that the most frequent PIs are type 1, especially for patients whose body weight is ≤ 50 kg. We observed a broad variability in the number or type of PI that were related to overdosed paracetamol prescriptions compared with the total of all recorded types of PI. These data suggest that a significant number of hospital pharmacists are unaware of the risks that adult patients with low body weight are exposed to when receiving four grams paracetamol/day over several days. Pharmacist educational programs are needed. Copyright © 2013. Published by Elsevier Masson SAS.

BN and BN oxide nanosheets based nanosensor for paracetamol adsorption: a first principles simulation

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Miguel Castro

2014-04-01

Full Text Available The effects that the adsorption of the paracetamol molecule produce on the structural and electronic properties of boron nitride (hBNNs; B27N27H18 and boron nitride oxide (hBNONs; B27N27H17 + O + (OH3 + COOH hexagonal symmetry nanosheets were studied by means of Density Functional Theory. The generalized gradient approximation proposed by Heyd—Scuseria—Ernzerhof ((HSEh1PBE―GGA was used in concert with 6-31G(d basis sets. Several candidate structures, 9 and 13 for the hBNNs―Paracetamol and BNONs―Paracetamol interactions, respectively, were used for the geometry optimization procedure. The results show that in the lowest energy absorption site the paracetamol molecule reaches a parallel orientation to the surface of the nanosheets, producing physisorption for hBNNs―Paracetamol and chemisorption for BNONs―Paracetamol. Besides, the adsorption process yields an increase of the polarity opening the possibility for the solubility and dispersion of these compounds. The paracetamol molecule promotes also a decrease of the reactivity parameter, which is crucial for biological applications of these systems. Referred to pristine hBNNs and BNONs, the work functions of hBNNs-Paracetamol and BNONs―Paracetamol are diminished. That is, these functionalized 2D systems yields appropriate conditions for field emission and they may be used as sensors of such pharmaceutical compound.

The relation between paracetamol use and asthma

DEFF Research Database (Denmark)

Shaheen, S; Potts, J; Gnatiuc, L

2008-01-01

Studies from the UK and the USA suggest that frequent use of paracetamol (acetaminophen) may increase the risk of asthma, but data across Europe are lacking.As part of a multi-centre case-control study organised by the GA(2)LEN network we have examined whether frequent paracetamol use is associated...... with adult asthma across Europe. The network compared 521 cases with a diagnosis of asthma and reporting asthma symptoms in the last 12 months with 507 controls with no diagnosis of asthma and no asthmatic symptoms in the last 12 months across 12 European centres. All cases and controls were selected from...... the same population defined by age (20-45 years) and place of residence.In a random effects meta-analysis, after controlling for confounders, the adjusted odds ratio for asthma associated with weekly use of paracetamol, compared with less frequent use, was 2.87 (95% CI: 1.49 to 5.37), P=0...

Saliva and dental erosion.

Science.gov (United States)

Buzalaf, Marília Afonso Rabelo; Hannas, Angélicas Reis; Kato, Melissa Thiemi

2012-01-01

Dental erosion is a multifactorial condition. The consideration of chemical, biological and behavioral factors is fundamental for its prevention and therapy. Among the biological factors, saliva is one of the most important parameters in the protection against erosive wear. This review discusses the role of salivary factors on the development of dental erosion. A search was undertaken on MeDLINe website for papers from 1969 to 2010. The keywords used in the research were "saliva", "acquired pellicle", "salivary flow", "salivary buffering capacity" and "dental erosion". Inclusion of studies, data extraction and quality assessment were undertaken independently and in duplicate by two members of the review team. Disagreements were solved by discussion and consensus or by a third party. Several characteristics and properties of saliva play an important role in dental erosion. Salivary clearance gradually eliminates the acids through swallowing and saliva presents buffering capacity causing neutralization and buffering of dietary acids. Salivary flow allows dilution of the acids. In addition, saliva is supersaturated with respect to tooth mineral, providing calcium, phosphate and fluoride necessary for remineralization after an erosive challenge. Furthermore, many proteins present in saliva and acquired pellicle play an important role in dental erosion. Saliva is the most important biological factor affecting the progression of dental erosion. Knowledge of its components and properties involved in this protective role can drive the development of preventive measures targeting to enhance its known beneficial effects.

Saliva and dental erosion

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Marília Afonso Rabelo Buzalaf

2012-10-01

Full Text Available Dental erosion is a multifactorial condition. The consideration of chemical, biological and behavioral factors is fundamental for its prevention and therapy. Among the biological factors, saliva is one of the most important parameters in the protection against erosive wear. Objective: This review discusses the role of salivary factors on the development of dental erosion. Material and Methods: A search was undertaken on MeDLINe website for papers from 1969 to 2010. The keywords used in the research were "saliva", "acquired pellicle", "salivary flow", "salivary buffering capacity" and "dental erosion". Inclusion of studies, data extraction and quality assessment were undertaken independently and in duplicate by two members of the review team. Disagreements were solved by discussion and consensus or by a third party. Results: Several characteristics and properties of saliva play an important role in dental erosion. Salivary clearance gradually eliminates the acids through swallowing and saliva presents buffering capacity causing neutralization and buffering of dietary acids. Salivary flow allows dilution of the acids. In addition, saliva is supersaturated with respect to tooth mineral, providing calcium, phosphate and fluoride necessary for remineralization after an erosive challenge. Furthermore, many proteins present in saliva and acquired pellicle play an important role in dental erosion. Conclusions: Saliva is the most important biological factor affecting the progression of dental erosion. Knowledge of its components and properties involved in this protective role can drive the development of preventive measures targeting to enhance its known beneficial effects.

TRAIL enhances paracetamol-induced liver sinusoidal endothelial cell death in a Bim- and Bid-dependent manner

Science.gov (United States)

Badmann, A; Langsch, S; Keogh, A; Brunner, T; Kaufmann, T; Corazza, N

2012-01-01

Paracetamol (acetaminophen, APAP) is a universally used analgesic and antipyretic agent. Considered safe at therapeutic doses, overdoses cause acute liver damage characterized by centrilobular hepatic necrosis. One of the major clinical problems of paracetamol-induced liver disease is the development of hemorrhagic alterations. Although hepatocytes represent the main target of the cytotoxic effect of paracetamol overdose, perturbations within the endothelium involving morphological changes of liver sinusoidal endothelial cells (LSECs) have also been described in paracetamol-induced liver disease. Recently, we have shown that paracetamol-induced liver damage is synergistically enhanced by the TRAIL signaling pathway. As LSECs are constantly exposed to activated immune cells expressing death ligands, including TRAIL, we investigated the effect of TRAIL on paracetamol-induced LSEC death. We here demonstrate for the first time that TRAIL strongly enhances paracetamol-mediated LSEC death with typical features of apoptosis. Inhibition of caspases using specific inhibitors resulted in a strong reduction of cell death. TRAIL appears to enhance paracetamol-induced LSEC death via the activation of the pro-apoptotic BH3-only proteins Bid and Bim, which initiate the mitochondrial apoptotic pathway. Taken together this study shows that the liver endothelial layer, mainly LSECs, represent a direct target of the cytotoxic effect of paracetamol and that activation of TRAIL receptor synergistically enhances paracetamol-induced LSEC death via the mitochondrial apoptotic pathway. TRAIL-mediated acceleration of paracetamol-induced cell death may thus contribute to the pathogenesis of paracetamol-induced liver damage. PMID:23254290

Effects of co-administration of chloroquine with paracetamol or ...

African Journals Online (AJOL)

The effects of co-administration of oral chloroquine with paracetamol or with ibuprofen on renal function were studied using 6 groups of New Zealand White rabbits. Group 1, the control group received only feed and water. The other groups (Groups 2-6) either received single therapies of paracetamol (10 mg/kg of body ...

Effects of saliva collection using cotton swabs on melatonin enzyme immunoassay.

Science.gov (United States)

Kozaki, Tomoaki; Lee, Soomin; Nishimura, Takayuki; Katsuura, Tetsuo; Yasukouchi, Akira

2011-01-10

Although various acceptable and easy-to-use devices have been used for saliva collection, cotton swabs are among the most common ones. Previous studies reported that cotton swabs yield a lower level of melatonin detection. However, this statistical method is not adequate for detecting an agreement between cotton saliva collection and passive saliva collection, and a test for bias is needed. Furthermore, the effects of cotton swabs have not been examined at lower melatonin level, a level at which melatonin is used for assessment of circadian rhythms, namely dim light melatonin onset (DLMO). In the present study, we estimated the effect of cotton swabs on the results of salivary melatonin assay using the Bland-Altman plot at lower level. Nine healthy males were recruited and each provided four saliva samples on a single day to yield a total of 36 samples. Saliva samples were directly collected in plastic tubes using plastic straws, and subsequently pipetted onto cotton swabs (cotton saliva collection) and into clear sterile tubes (passive saliva collection). The melatonin levels were analyzed in duplicate using commercially available ELISA kits. The mean melatonin concentration in cotton saliva collection samples was significantly lower than that in passive saliva collection samples at higher melatonin level (>6 pg/mL). The Bland-Altman plot indicated that cotton swabs causes relative and proportional biases in the assay results. For lower melatonin level (<6 pg/mL), although the BA plots didn't show proportional and relative biases, there was no significant correlation between passive and cotton saliva collection samples. Our findings indicate an interference effect of cotton swabs on the assay result of salivary melatonin at lower melatonin level. Cotton-based collection devices might, thus, not be suitable for assessment of DLMO.

SALIVA SEBAGAI UJI SARING OSTEOPOROSIS

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Niniarty Z. Djamal

2015-07-01

Full Text Available Osteoporosis is a metabolic bone disease, and is characterized by low bone mass and microstructure deterioration of the bone, which leads to increased risk of fracture. Biomarker of bone metabolism can be seen as beginning of bone loss and first detection before imbalanced bone turnover comes. Biomarker of bone formation as serum bone alkaline fosfatase, osteocalcin (OC, procollagen type I, and biomarker of bone resorption as urine pyridinoline (Pyd and deoxypyridinoline (Dpd crosslinks, hydroxyprolin. The simultaneous examination of serum OC and urine Pyd or Dpd as a very good screening test for determination of bone imbalanced at the moment of the menopausal or the beginning of the pasca menopausal. Saliva as a potential diagnostic fluid for the assessment of osteoporosis biomarker concentrations. The study found elevated three classic warning signs for osteopororsis os OC, Dpd and 116 in the saliva of sheep without ovaries, which were similar to the levels of signs found in their blood and urine. Expectations, that the test may become available within five years and one day the test may be able to be performed at home like pregnancy test. Osteoporosis biomarker in saliva suggested detected of bone mass density easier. Beside that can be used as a method of early diagnostic and as a monitor therapy that as salinity of the examinations of bone mass on radiology.

Dose-dependent adsorptive capacity of activated charcoal for gastrointestinal decontamination of a simulated paracetamol overdose in human volunteers

DEFF Research Database (Denmark)

Gude, Anne-Bolette Jill; Hoegberg, Lotte Christine Groth; Riis Angelo, Helle

2010-01-01

The amount of activated charcoal needed to treat drug overdoses has arbitrarily been set at a charcoal-drug ratio of 10:1. Recent in vitro studies have shown a larger adsorptive capacity for activated charcoal when used in a model of paracetamol overdose. In the present study, we investigated...... whether this reserve capacity exists in vivo. This is clinically relevant in cases of large overdoses or if the full standard dose of 50 g activated charcoal cannot be administered. We performed a randomized, cross-over study (n = 16). One hour after a standard breakfast, 50 mg/kg paracetamol...... was administered, followed 1 hr later by an activated charcoal-Water slurry containing 50 (control), 25 or 5 g activated charcoal. The areas under the serum concentration-time curve (AUC) for paracetamol were used to estimate the efficacy of each activated charcoal dose. The AUC of the 25-g dose was found...

Degradation of Paracetamol by Photolysis Using C-N-codoped TiO2

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Vanny Yulia Safitri

2017-11-01

Full Text Available Paracetamol is generally used as analgesic and antipyretic drugs. Contamination paracetamol in the environment can occur because of waste material disposal from production site and immediate disposal of household that cause water pollution. Paracetamol is degraded by photolysis method under irradiation 10 watt UV-light (λ=365 nm, visible-light (Philips LED 13 watt 1400 lux and solar-light with and without addition C-N-codoped TiO2catalyst. The solution is analyzed by UV-Vis spectrophotometer at λ 200-400 nm. Optimum weight of C-N-codoped TiO2 catalyst obtained is 20 mg under UV-light photolysis. Paracetamol 4 mg/L is degraded 45.48% after 120 minutes under UV-light irradiation without catalyst, and increases to be 69.31% by using 20 mg catalyst. While degradation percentage of paracetamol is 16.96 % without catalyst, the percentage increases to be 34.29% after using 20 mg catalyst for 120 minutes photolysis under visible-light. Degradation of paracetamol by solar light achieves only 12.27% in absance of catalyst for 120 minutes irradiation, but it increases significantly until 70.39% in presence of 20 mg catalyst.

Creatine metabolism: detection of creatine and guanidinoacetate in saliva of healthy subjects.

Science.gov (United States)

Martínez, Lidia D; Bezard, Miriam; Brunotto, Mabel; Dodelson de Kremer, Raquel

2016-04-01

Creatine (Cr) plays an important role in storage and transmission of phosphate-bound energy. Cerebral creatine deficiency syndromes comprise three inherited defects in Cr biosynthesis and transport. The aim of this study was to investigate whether Cr and Guanidinoacetate (GAA) can be detected in saliva of healthy subjects and to establish the relationship between salivary and plasma levels of these molecules. An adapted gas chromatography (GC) method is described for the quantification of Cr and GAA biomarkers in saliva. Reference values were established for GAA and Cr in saliva. These values were age dependent (p= 0.001). No difference between genders was observed. We detected a difference between GAA and Cr concentrations in saliva and in plasma. The GC method for simultaneous determination of GAA and Cr in human saliva is fast, reliable, sensitive, non-invasive and precise to use as a biochemical approach in early detection of cerebral creatine deficiency syndromes. Sociedad Argentina de Investigación Odontológica.

Effects of saliva collection using cotton swabs on melatonin enzyme immunoassay

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Katsuura Tetsuo

2011-01-01

Full Text Available Abstract Background Although various acceptable and easy-to-use devices have been used for saliva collection, cotton swabs are among the most common ones. Previous studies reported that cotton swabs yield a lower level of melatonin detection. However, this statistical method is not adequate for detecting an agreement between cotton saliva collection and passive saliva collection, and a test for bias is needed. Furthermore, the effects of cotton swabs have not been examined at lower melatonin level, a level at which melatonin is used for assessment of circadian rhythms, namely dim light melatonin onset (DLMO. In the present study, we estimated the effect of cotton swabs on the results of salivary melatonin assay using the Bland-Altman plot at lower level. Methods Nine healthy males were recruited and each provided four saliva samples on a single day to yield a total of 36 samples. Saliva samples were directly collected in plastic tubes using plastic straws, and subsequently pipetted onto cotton swabs (cotton saliva collection and into clear sterile tubes (passive saliva collection. The melatonin levels were analyzed in duplicate using commercially available ELISA kits. Results The mean melatonin concentration in cotton saliva collection samples was significantly lower than that in passive saliva collection samples at higher melatonin level (>6 pg/mL. The Bland-Altman plot indicated that cotton swabs causes relative and proportional biases in the assay results. For lower melatonin level ( Conclusion Our findings indicate an interference effect of cotton swabs on the assay result of salivary melatonin at lower melatonin level. Cotton-based collection devices might, thus, not be suitable for assessment of DLMO.

Interleukin-6 and neopterin levels in the serum and saliva of patients with Lichen planus and oral Lichen planus.

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Abdel-Haq, Ayman; Kusnierz-Cabala, Beata; Darczuk, Dagmara; Sobuta, Eliza; Dumnicka, Paulina; Wojas-Pelc, Anna; Chomyszyn-Gajewska, Maria

2014-11-01

Lichen planus together with its oral variant is a chronic, inflammatory disease of the skin and the mucosa of unclear aetiology and with an unpredictable course that still poses a major problem in terms of diagnosis and treatment. The objective of this study was to assess the concentrations of interleukin-6 (IL-6) and neopterin in saliva and serum of patients with lichen planus (including reticular and erosive form of oral lichen planus) and to compare them with the concentrations observed in healthy controls. The study material comprised serum and saliva samples from 56 patients diagnosed with lichen planus and 56 healthy volunteers. The ELISA test was used to measure concentrations of IL-6 and neopterin in the serum and saliva of the study participants. The concentrations of IL-6 in saliva and serum of patients with lichen planus were significantly higher than in controls (P = 0.0002; P oral lichen planus had significantly higher IL-6 concentrations in their saliva compared to patients with reticular form of disease (P = 0.01). The concentrations of neopterin were significantly higher in the serum but not in saliva of lichen planus patients vs. controls (P lichen planus as well as the salivary concentrations of IL-6. The differences observed in IL-6 levels in patients with erosive-atrophic forms of oral lichen planus may indicate a substantial role played by the cytokine in the disease. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Acetaminophen/paracetamol: A history of errors, failures and false decisions.

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Brune, K; Renner, B; Tiegs, G

2015-08-01

Acetaminophen/paracetamol is the most widely used drug of the world. At the same time, it is probably one of the most dangerous compounds in medical use, causing hundreds of deaths in all industrialized countries due to acute liver failure (ALF). Publications of the last 130 years found in the usual databases were analyzed. Personal contacts existed to renowned researchers having contributed to the medical use of paracetamol and its precursors as H.U. Zollinger, S. Moeschlin, U. Dubach, J. Axelrod and others. Further information is found in earlier reviews by Eichengrün, Rodnan and Benedek, Sneader, Brune; comp. references. The history of the discovery of paracetamol starts with an error (active against worms), continues with a false assumption (paracetamol is safer than phenacetin), describes the first side-effect 'epidemy' (phenacetin nephropathy, drug-induced interstitial nephritis) and ends with the discovery of second-generation problems due to the unavoidable production of a highly toxic metabolite of paracetamol N-acetyl-p-benzoquinone imine (NAPQI) that may cause not only ALF and kidney damage but also impaired development of the fetus and the newborn child. It appears timely to reassess the risk/benefit ratio of this compound. © 2014 European Pain Federation - EFIC®

Quantitative analysis of leaching of different metals in human saliva from dental casting alloys: An in vivo study

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Ramashanker Siddharth

2015-01-01

Conclusion: Metal-based dentures show maximum leaching immediately after wearing of the prosthesis which decreased significantly over the period of 3 days. Cr and Mn were the metal ions mainly found in saliva of cast partial denture wearer. No concentration of cobalt, molybdenum (Mo and iron (Fe was found in saliva of metal base denture wearer. There was a significant change in concentration of elutes in saliva in first 72 h/3 days making time an effective variable was observed.

Rapid antemortem detection of CWD prions in deer saliva.

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Davin M Henderson

Full Text Available Chronic wasting disease (CWD is an efficiently transmitted prion disease of cervids, now identified in 22 United States, 2 Canadian provinces and Korea. One hallmark of CWD is the shedding of infectious prions in saliva, as demonstrated by bioassay in deer. It is also clear that the concentration of prions in saliva, blood, urine and feces is much lower than in the nervous system or lymphoid tissues. Rapid in vitro detection of CWD (and other prions in body fluids and excreta has been problematic due to the sensitivity limits of direct assays (western blotting, ELISA and the presence of inhibitors in these complex biological materials that hamper detection. Here we use real-time quaking induced conversion (RT-QuIC to demonstrate CWD prions in both diluted and prion-enriched saliva samples from asymptomatic and symptomatic white-tailed deer. CWD prions were detected in 14 of 24 (58.3% diluted saliva samples from CWD-exposed white-tailed deer, including 9 of 14 asymptomatic animals (64.2%. In addition, a phosphotungstic acid enrichment enhanced the RT-QuIC assay sensitivity, enabling detection in 19 of 24 (79.1% of the above saliva samples. Bioassay in Tg[CerPrP] mice confirmed the presence of infectious prions in 2 of 2 RT-QuIC-positive saliva samples so examined. The modified RT-QuIC analysis described represents a non-invasive, rapid ante-mortem detection of prions in complex biologic fluids, excreta, or environmental samples as well as a tool for exploring prion trafficking, peripheralization, and dissemination.

Paracetamol in therapeutic dosages and acute liver injury: causality assessment in a prospective case series

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Castellote José

2011-07-01

Full Text Available Abstract Background Acute liver injury (ALI induced by paracetamol overdose is a well known cause of emergency hospital admission and death. However, there is debate regarding the risk of ALI after therapeutic dosages of the drug. The aim is to describe the characteristics of patients admitted to hospital with jaundice who had previous exposure to therapeutic doses of paracetamol. An assessment of the causality role of paracetamol was performed in each case. Methods Based on the evaluation of prospectively gathered cases of ALI with detailed clinical information, thirty-two cases of ALI in non-alcoholic patients exposed to therapeutic doses of paracetamol were identified. Two authors assessed all drug exposures by using the CIOMS/RUCAM scale. Each case was classified into one of five categories based on the causality score for paracetamol. Results In four cases the role of paracetamol was judged to be unrelated, in two unlikely, and these were excluded from evaluation. In seven of the remaining 26 cases, the RUCAM score associated with paracetamol was higher than that associated with other concomitant medications. The estimated incidence of ALI related to the use of paracetamol in therapeutic dosages was 0.4 per million inhabitants older than 15 years of age and per year (99%CI, 0.2-0.8 and of 10 per million paracetamol users-year (95% CI 4.3-19.4. Conclusions Our results indicate that paracetamol in therapeutic dosages may be considered in the causality assessment in non-alcoholic patients with liver injury, even if the estimated incidence of ALI related to paracetamol appears to be low.

A Lab-on-a-Chip-Based Non-Invasive Optical Sensor for Measuring Glucose in Saliva

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Dong Geon Jung

2017-11-01

Full Text Available A lab-on-a-chip (LOC-based non-invasive optical sensor for measuring glucose in saliva was fabricated. Existing glucose sensors utilizing blood require acquisition of a blood sample by pricking the finger, which is painful and inconvenient. To overcome these limitations, we propose a non-invasive glucose sensor with LOC, micro-electro-mechanical system and optical measurement technology. The proposed sensor for measuring glucose in saliva involves pretreatment, mixing, and measurement on a single tiny chip. Saliva containing glucose and glucose oxidase for glucose oxidation are injected through Inlets 1 and 2, respectively. Next, H2O2 is produced by the reaction between glucose and glucose oxidase in the pretreatment part. The saliva and generated H2O2 are mixed with a colorizing agent injected through Inlet 3 during the mixing part and the absorbance of the colorized mixture is measured in the measurement part. The absorbance of light increases as a function of glucose concentration at a wavelength of 630 nm. To measure the absorbance of the colorized saliva, a light-emitting diode with a wavelength of 630 nm and a photodiode were used during the measurement part. As a result, the measured output current of the photodiode decreased as glucose concentration in the saliva increased.

An assessment of the quality of various brands of paracetamol ...

African Journals Online (AJOL)

To assess the seriousness of the global counterfeiting problem, we quantified the amount of active ingredient present in paracetamol tablets by various official and non-official methods. Eight brands of Paracetamol 500mg tablets were assessed using the quality control parameters of weight uniformity, active ingredient ...

The majority of sick children receive paracetamol during the winter

DEFF Research Database (Denmark)

Ertmann, Ruth; Møller, Janne Julie; Waldorff, Frans Boch

2012-01-01

Even though fever is a common symptom in childhood, it often worries parents and they may try to reduce discomfort by giving the child paracetamol, which is currently the most commonly sold over-the-counter medicine. The objective of this study was to investigate parent-administered paracetamol...

Paracetamol (acetaminophen) with or without an antiemetic for acute migraine headaches in adults.

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Derry, Sheena; Moore, R Andrew

2013-04-30

This is an updated version of the original Cochrane review published in Issue 11, 2010 (Derry 2010). Migraine is a common, disabling condition and a burden for the individual, health services and society. Many sufferers choose not to, or are unable to, seek professional help and rely on over-the-counter analgesics. Co-therapy with an antiemetic should help to reduce nausea and vomiting, which are commonly associated with migraine. To determine the efficacy and tolerability of paracetamol (acetaminophen), alone or in combination with an antiemetic, compared with placebo and other active interventions in the treatment of acute migraine in adults. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and the Oxford Pain Relief Database for studies through 4 October 2010 for the original review, and to 13 February 2013 for the update. Two clinical trials registers (ClinicalTrials.gov and gsk-clinicalstudyregister.com) were also searched on both occasions. We included randomised, double-blind, placebo- or active-controlled studies using self-administered paracetamol to treat a migraine headache episode, with at least 10 participants per treatment arm. Two review authors independently assessed trial quality and extracted data. Numbers of participants achieving each outcome were used to calculate relative risk and numbers needed to treat (NNT) or harm (NNH) compared with placebo or other active treatment. Searches for the update identified one additional study for inclusion. Eleven studies (2942 participants, 5109 attacks) compared paracetamol 1000 mg, alone or in combination with an antiemetic, with placebo or other active comparators, mainly sumatriptan 100 mg. For all efficacy outcomes paracetamol was superior to placebo, with NNTs of 12 (19% response with paracetamol, 10% with placebo), 5.0 (56% response with paracetamol, 36% with placebo) and 5.2 (39% response with paracetamol, 20% with placebo) for 2-hour pain-free and 2- and 1

Some Biological Activities of Malaysian Leech Saliva Extract

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Abdualrahman M. Abdualkader

2011-12-01

Full Text Available Normal 0 21 false false false MS X-NONE AR-SA Leeches were fed on the phagostimulatory solution through parafilm membrane. The satiated leeches were forced to regurgitate the solution by soaking them in an ice-container. The anticoagulant activity was ascertained using thrombin time assay (TT. The result revealed that the saliva concentration which increases TT by 100% (IC100 is 43.205µg/ml plasma. The antimicrobial activity of the saliva was tested against several bacterial spp. (E.coli, P.aeruginosa, B.cereus, Sal.typhi and S.aureus  and fungi spp. (C.albicans and C.neoformans. It was found that saliva has an inhibition activity against Sal.typhi (minimal inhibitory concentration MIC 78.253µg/ml, S.aureus (MIC 78.253µg/ml and E.coli (MIC 121.256µg/ml.ABSTRAK: Pacat-pacat diberi makan larutan phagostimulatory menerusi membran parafilem. Pacat-pacat yang kekenyangan itu dipaksa memuntahkan larutan tersebut dengan direndam di dalam bekas berisi ais. Aktiviti antigumpal ditentukan menggunakan cerakin masa trombin (TT. Keputusan menunjukkan kepekatan air liur pacat menyebabkan pertambahan TT sebanyak 100% (IC100 iaitu 43.205µg/ml plasma. Aktiviti antimikrob air liur telah diuji dengan pelbagai jenis bakteria (E.coli, P.aeruginosa, B.cereus, Sal.typhi dan S.aureus dan pelbagai jenis kulat (C.albicans and C.neoformans. Didapati air liur menghasilkan aktiviti perencatan terhadap Sal.typhi (kepekatan perencat minima (Minimal inhibitory concentration - MIC 78.253µg/ml, S.aureus (MIC 78.253µg/ml dan E.coli (MIC 121.256µg/ml.

Paracetamol (acetaminophen) poisoning.

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Park, B Kevin; Dear, James W; Antoine, Daniel J

2015-10-19

Paracetamol directly causes around 150 deaths per year in UK. We conducted a systematic overview, aiming to answer the following clinical question: What are the effects of treatments for acute paracetamol poisoning? We searched: Medline, Embase, The Cochrane Library, and other important databases up to October 2014 (Clinical Evidence overviews are updated periodically; please check our website for the most up-to-date version of this overview). At this update, searching of electronic databases retrieved 127 studies. After deduplication and removal of conference abstracts, 64 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 46 studies and the further review of 18 full publications. Of the 18 full articles evaluated, one systematic review was updated and one RCT was added at this update. In addition, two systematic reviews and three RCTs not meeting our inclusion criteria were added to the Comment sections. We performed a GRADE evaluation for three PICO combinations. In this systematic overview we categorised the efficacy for six interventions, based on information about the effectiveness and safety of activated charcoal (single or multiple dose), gastric lavage, haemodialysis, liver transplant, methionine, and acetylcysteine.

Quality control and stability study of 100 mg/ml paracetamol oral drops

International Nuclear Information System (INIS)

Garcia Penna, Caridad M.; Montes de Oca Porto, Yanet; Salomon Izquierdo, Suslebys

2013-01-01

Paracetamol is an effective analgesic and antipyretic drug of the non-steroidal anti-inflammatory drug group. Paracetamol oral drops are indicated for use in infant population aged up to 5 years to relieve fever, headache, toothache and symptomatic relief of common cold. To validate two analytical methods for the quality control and the stability study and to study the stability of 100 mg/ml Paracetamol oral drops made in Cuba

Naproxen, paracetamol and pamabrom versus paracetamol, pyrilamine and pamabrom in primary dysmenorrhea: a randomized, double-blind clinical trial

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Mario I. Ortiz

2016-10-01

Full Text Available Resumen INTRODUCCIÓN La dismenorrea primaria es causada por la descarga de las prostaglandinas en el tejido uterino. Por lo tanto, los fármacos antiinflamatorios no esteroideos son la terapia inicial para la dismenorrea. El tratamiento para la dismenorrea puede incluir la administración de monoterapia o la combinación de fármacos. Sin embargo, la evidencia clínica científica sobre la eficacia de los medicamentos con dos o tres fármacos combinados es escasa o ausente. OBJETIVO Evaluar y comparar la eficacia y seguridad de dos combinaciones, en dosis fija y oral para el alivio de los síntomas de la dismenorrea primaria en mujeres mexicanas. Basados en la fisiopatología de la dismenorrea primaria, se utilizó una combinación comercializada en México de paracetamol, pirilamina y pamabrom. El comparador seleccionado fue un medicamento que contiene naproxeno sódico, paracetamol y pamabrom. MÉTODOS Se realizó un estudio en un solo centro, a doble ciego, experimental, paralelo y aleatorizado. Las pacientes con dismenorrea primaria que se incluyeron fueron mayores de 17 años de edad y con una intensidad del dolor mayor a 45 milímetros en una escala visual analógica. Las pacientes fueron aleatorizadas para recibir tabletas con naproxeno sódico, paracetamol y pamabrom o tabletas con paracetamol, pirilamina y pamabrom para un ciclo menstrual. Se evaluó la intensidad de la sintomatología y el dolor de las pacientes a lo largo de un período menstrual. Se utilizó análisis estadístico descriptivo e inferencial. RESULTADOS Se incluyó una población con intención de tratar de 91 mujeres, con una edad media de 21,3 ± 3,2 años la cual recibió tabletas de paracetamol, pirilamina y pamabrom. Otras 98 participantes, con una edad media de 21,0 ± 3,2 años, recibieron tabletas de naproxeno sódico, paracetamol y pamabrom. Las evaluaciones de dolor de las participantes con la escala visual analógica durante el ciclo menstrual demostraron

Paracetamol (acetaminophen) for patent ductus arteriosus in preterm or low birth weight infants.

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Ohlsson, Arne; Shah, Prakeshkumar S

2018-04-06

In preterm newborns, the ductus arteriosus frequently fails to close and the infants require medical or surgical closure of the patent ductus arteriosus (PDA). A PDA can be treated surgically; or medically with one of two prostaglandin inhibitors, indomethacin or ibuprofen. Case reports suggest that paracetamol may be an alternative for the closure of a PDA. An association between prenatal or postnatal exposure to paracetamol and later development of autism or autism spectrum disorder has been reported. To determine the effectiveness and safety of intravenous or oral paracetamol compared with placebo or no intervention, intravenous indomethacin, intravenous or oral ibuprofen, or with other cyclo-oxygenase inhibitors for treatment of an echocardiographically diagnosed PDA in preterm or low birth weight infants. We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2017, Issue 10), MEDLINE via PubMed (1966 to 6 November 2017), Embase (1980 to 6 November 2017), and CINAHL (1982 to 6 November 2017). We searched clinical trial databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials (RCT) and quasi-randomised trials. We included RCTs in which paracetamol was compared to no intervention, placebo or other agents used for closure of PDA irrespective of dose, duration and mode of administration in preterm (≤ 34 weeks' postmenstrual age) infants. We both reviewed the search results and made a final selection of potentially eligible articles by discussion. We included studies of both prophylactic and therapeutic use of paracetamol. We performed data collection and analyses in accordance with the methods of the Cochrane Neonatal Review Group. We used the GRADE approach to assess the quality of evidence for the following outcomes when data were available: failure of ductal closure after the first course of treatment; neurodevelopmental impairment

Comparative assessment of saliva and plasma for drug bioavailability and bioequivalence studies in humans

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Nasir M. Idkaidek

2017-07-01

Conclusion: Our results suggest that there is a potential in BA/BE studies for saliva to be considered as a surrogate for plasma concentration, which goes along with drug regulations. The use of saliva instead of plasma in such studies makes them non-invasive, easy and with a lower clinical burden.

COMPARISON OF THE EFFECTS OF INTERCOSTAL NERVE BLOCK WITH ROPIVACAINE AND INTRAVENOUS PARACETAMOL INFUSION TO INTRAVENOUS PARACETAMOL INFUSION ALONE FOR PAIN CONTROL AFTER OPEN CHOLECYSTECTOMY

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Somnath Dey

2017-11-01

Full Text Available BACKGROUND Postoperative pain after open cholecystectomy is associated with respiratory dysfunction, increased stress response and prolonged hospital stay. We compare intravenous paracetamol (7.5 mg/kg plus intercostal nerve block with local anaesthetic ropivacaine 0.5% to intravenous paracetamol (15 mg/kg on pain control after open cholecystectomy. MATERIALS AND METHODS 140 patients, who underwent for open cholecystectomy, were randomly divided into two groups of 70. The patients were randomly allocated to any of the following two groups depending upon the drug used for analgesia (Group P or Group I Intravenous paracetamol 15 mg/kg was given to patients of group P and paracetamol 7.5 mg/kg with Intercostal nerve block in right side 6-10 intercostal nerves with 2 ml local anaesthetic ropivacaine 0.5% in each space was given to patients of group I just after intubation before incision. When the patients were transferred to postoperative recovery room, intensity of pain was recorded by response from the patients using 100 mm linear visual analogue scale ranging from 0 to 100. The pain scoring was done in the immediate postoperative period (when the patient was able to communicate in the post anaesthesia care unit, at 30 minutes, 1 hr. then hourly up to 24 hrs. till patient complained of pain with VAS score 40 or more. RESULTS The severity of pain in VAS score was lower in immediate postoperative period, at 30 minutes, 1 hour and 2 hours postoperatively in group I than the group P and those were statistically significant (p<0.001. Duration of analgesia also significantly lower in group I. Mean duration of analgesia in group P is 161.9 ± 42.6 min and in group I is 241.3 ± 44.2 min (p<0.001. CONCLUSION Adding Intercostal nerve block to intravenous infusion of Paracetamol infusion (7.5 mg/kg is better than sole intravenous infusion of Paracetamol (15 mg/kg in controlling pain severity even after reducing dose of paracetamol after open

Preventive Effect of Intrathecal Paracetamol on Spinal Cord Injury in Rats

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Sahin, Murat; Sayar, Ilyas; Peker, Kemal; Gullu, Huriye; Yildiz, Huseyin

2014-01-01

Background: Ischemic injury of the spinal cord during the surgical repair of thoracoabdominal aortic aneurysms might lead to paraplegia. Although a number of different mechanisms have been proposed, the exact cause of paraplegia has remained unknown, hampering the development of effective pharmacologic or other strategies for prevention of this condition. A number of studies suggested that cyclooxygenases (COX) contribute to neural breakdown; thus, COX inhibitors might reduce injury. Objectives: We aimed to assess the preventive effect of intrathecal (IT) pretreatment with paracetamol on spinal cord injury in a rat model. Materials and Methods: This experimental study was performed in Ataturk University Animal Research Laboratory Center, Erzurum, Turkey. Adult male Wistar rats were randomly allocated to three experimental groups (n = 6) to receive IT physiologic saline (controls), 50 µg of paracetamol, or 100 µg paracetamol one hour before induction of spinal cord ischemia. Six other rats were considered as the sham group. For the assessment of ischemic injury, motor functions of the hind limbs and histopathologic changes of the lumbar spinal cord were evaluated. Additional 20 rats were divided into two equal groups for the second part of the study where the survival rates were recorded in controls and in animals receiving 100 µg of paracetamol during the 28-day observation period. Results: Pretreatment with 100 µg of paracetamol resulted in a significant improvement in motor functions and histopathologic findings (P < 0.05). Despite a higher rate of survival in 100 µg of paracetamol group (70%) at day 28, the difference was not statistically significant in comparison with controls. Conclusions: Our results suggest a protective effect of pretreatment with IT paracetamol on ischemic spinal cord injury during thoracolumbar aortic aneurysm surgery. PMID:25763224

Prenatal paracetamol exposure and child neurodevelopment: a sibling-controlled cohort study

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Brandlistuen, Ragnhild Eek; Ystrom, Eivind; Nulman, Irena; Koren, Gideon; Nordeng, Hedvig

2013-01-01

Background Paracetamol is used extensively during pregnancy, but studies regarding the potential neurodevelopmental sequelae of foetal paracetamol exposure are lacking. Method Between 1999 and 2008 all pregnant Norwegian women were eligible for recruitment into the prospective Norwegian Mother and Child Cohort Study. The mothers were asked to report on their use of paracetamol at gestational weeks 17 and 30 and at 6 months postpartum. We used data on 48 631 children whose mothers returned the 3-year follow-up questionnaire by May 2011. Within this sample were 2919 same-sex sibling pairs who were used to adjust for familial and genetic factors. We modelled psychomotor development (communication, fine and gross motor development), externalizing and internalizing behaviour problems, and temperament (emotionality, activity, sociability and shyness) based on prenatal paracetamol exposure using generalized linear regression, adjusting for a number of factors, including febrile illness, infections and co-medication use during pregnancy. Results The sibling-control analysis revealed that children exposed to prenatal paracetamol for more than 28 days had poorer gross motor development [β 0.24, 95% confidence interval (CI) 0.12–0.51], communication (β 0.20, 95% CI 0.01–0.39), externalizing behaviour (β 0.28, 95% CI 0.15–0.42), internalizing behaviour (β 0.14, 95% CI 0.01–0.28), and higher activity levels (β 0.24, 95% CI 0.11–0.38). Children exposed prenatally to short-term use of paracetamol (1–27 days) also had poorer gross motor outcomes (β 0.10, 95% CI 0.02–0.19), but the effects were smaller than with long-term use. Ibuprofen exposure was not associated with neurodevelopmental outcomes. Conclusion Children exposed to long-term use of paracetamol during pregnancy had substantially adverse developmental outcomes at 3 years of age. PMID:24163279

Paracetamol treatment for patent ductus arteriosus: practice and attitudes in Australia and New Zealand.

Science.gov (United States)

Dowd, L A; Wheeler, B J; Al-Sallami, H S; Broadbent, R S; Edmonds, L K; Medlicott, N J

2018-04-03

To describe the current clinical practices and attitudes of neonatologists towards paracetamol treatment of PDA in Australia (AU) and New Zealand (NZ). A web-based survey of all neonatologists registered under the 2017 Australia New Zealand Neonatal Network (ANZNN) was conducted. The response rate for the survey was 67%, (141/210). Of those respondents, 37% stated their unit had a written policy outlining how to treat patent ductus arteriosus (PDA). Of the written policies, 53% mentioned paracetamol treatment. The majority of the respondents (70%) have prescribed paracetamol for PDA closure. When comparing between countries, 79% of AU respondents had compared with 44% of NZ respondents. Successful ductal closure in the infants who received paracetamol was anecdotally reported by 61% of respondents. The main reasons for clinicians not prescribing paracetamol were due to preferential NSAID use (61%) and lack of evidence to indicate efficacy (49%). Many neonatologists in AU and NZ have prescribed paracetamol for PDA closure. However, considerable practice variations exist. The results from this study suggest there may be a role for paracetamol in the treatment of PDA, however, further research is required to clarify the optimal use and provide evidence of efficacy.

Longitudinal Study of Hepatitis A Infection by Saliva Sampling: The Kinetics of HAV Markers in Saliva Revealed the Application of Saliva Tests for Hepatitis A Study

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Amado Leon, Luciane Almeida; de Almeida, Adilson José; de Paula, Vanessa Salete; Tourinho, Renata Santos; Villela, Daniel Antunes Maciel; Gaspar, Ana Maria Coimbra; Lewis-Ximenez, Lia Laura; Pinto, Marcelo Alves

2015-01-01

Despite the increasing numbers of studies investigating hepatitis A diagnostic through saliva, the frequency and the pattern of hepatitis A virus (HAV) markers in this fluid still remains unknown. To address this issue, we carried on a longitudinal study to examine the kinetics of HAV markers in saliva, in comparison with serum samples. The present study followed-up ten patients with acute hepatitis A infection during 180 days post diagnosis (dpd). Total anti-HAV was detected in paired serum and saliva samples until the end of the follow-up, showing a peak titer at 90th. However, total anti-HAV level was higher in serum than in saliva samples. This HAV marker showed a probability of 100% to be detected in both serum and saliva during 180 dpd. The IgM anti-HAV could be detected in saliva up to 150 dpd, showing the highest frequency at 30th, when it was detected in all individuals. During the first month of HAV infection, this acute HAV marker showed a detection probability of 100% in paired samples. The detection of IgM anti-HAV in saliva was not dependent on its level in serum, HAV-RNA detection and/or viral load, since no association was found between IgM anti-HAV positivity in saliva and any of these parameter (p>0.05). Most of the patients (80%) were found to contain HAV-RNA in saliva, mainly at early acute phase (30th day). However, it was possible to demonstrate the HAV RNA presence in paired samples for more than 90 days, even after seroconversion. No significant relationship was observed between salivary HAV-RNA positivity and serum viral load, demonstrating that serum viral load is not predictive of HAV-RNA detection in saliva. Similar viral load was seen in paired samples (on average 104 copies/mL). These data demonstrate that the best diagnostic coverage can be achieved by salivary anti-HAV antibodies and HAV-RNA tests during 30–90 dpd. The long detection and high probability of specific-HAV antibodies positivity in saliva samples make the assessment of

[Analgesic effect and clinical tolerability of the combination of paracetamol 500 mg and caffeine 50 mg versus paracetamol 400 mg and dextropropoxyphene 30 mg in back pain].

Science.gov (United States)

Kuntz, D; Brossel, R

1996-09-07

A double-blind randomized multicentric study was performed to test the hypothesis that the analgesic effect of paracetamol-cafeine is equivalent to that of paracetamol-dextropropoxyphen in patients suffering from pain due to osteoarthritis of the spine. Rhumatologists included 124 patients who were randomized into two groups of 62 each. Pain was measured daily during the seven-day treatment Huskisson's Analog Visual Scales; 112 were per protocol and evaluable. The two treatment groups were statistically similar for demographics, vital signs, medical and treatment history. A majority of them had pain located at the lumbar spine only; the other patients had either pain at the cervical or dorsal spine or at several sites. At the end of the week there was a major reduction in pain level: 51.2% in patients given paracetamol-cafeine and 47.0% in those given paracetamol-dextropropoxyphen. The main criteria of efficacy--the percentage of success (decrease of pain > 50%)--was similar in the two groups as well in the intention-to-treat population (p = 0.01) as the per protocol population (p = 0.028). Kinetics of pain decrease during the first day of treatment were assessed with an hourly evaluation during the six first hours and at the 12th hour. There was no difference between the two groups. There was no serious adverse event and the frequency and intensity of the adverse events were similar in the two groups. The potentializing action of cafeine on paracetamol-induced pain relief enables a degree of pain relief equivalent to that of a combination using an analgesic with a peripheral action, paracetamol, and another with a central action, dextropoxyphen. The fact that the paracetamol-cafeine combination does not have a central action avoids secondary effects induced by central analgesics (drowsiness, constipation) in patients with osteoarthritis back pain.

Salivary glucose concentration and excretion in normal and diabetic subjects.

Science.gov (United States)

Jurysta, Cedric; Bulur, Nurdan; Oguzhan, Berrin; Satman, Ilhan; Yilmaz, Temel M; Malaisse, Willy J; Sener, Abdullah

2009-01-01

The present report aims mainly at a reevaluation of salivary glucose concentration and excretion in unstimulated and mechanically stimulated saliva in both normal and diabetic subjects. In normal subjects, a decrease in saliva glucose concentration, an increase in salivary flow, but an unchanged glucose excretion rate were recorded when comparing stimulated saliva to unstimulated saliva. In diabetic patients, an increase in salivary flow with unchanged salivary glucose concentration and glucose excretion rate were observed under the same experimental conditions. Salivary glucose concentration and excretion were much higher in diabetic patients than in control subjects, whether in unstimulated or stimulated saliva. No significant correlation between glycemia and either glucose concentration or glucose excretion rate was found in the diabetic patients, whether in unstimulated or stimulated saliva. In the latter patients, as compared to control subjects, the relative magnitude of the increase in saliva glucose concentration was comparable, however, to that of blood glucose concentration. The relationship between these two variables was also documented in normal subjects and diabetic patients undergoing an oral glucose tolerance test.

Investigation of Fe and Ca in non-stimulated human saliva using NAA

Science.gov (United States)

de Medeiros, J. A. G.; Zamboni, C. B.; Kovacs, L.; Lewgoy, H. R.

2015-07-01

In this study we investigated non-stimulated human whole saliva of healthy subjects and patients with periodontal disease using Neutron Activation Analysis technique (NAA). The measurements were performed in the IEA-R1 nuclear reactor at IPEN-CNEN/SP. We found considerable metabolic changes mainly in Fe and Ca concentration in whole saliva of periodontal patients. These data are useful for identifying or preventing this oral disease in the Brazilian population.

A device for the collection of submandibular saliva.

Science.gov (United States)

Hanning, Sara; Motoi, Lidia; Medlicott, Natalie; Swindells, Stephen

2012-03-01

The objective of this study was to describe the construction of a non-invasive device for the collection of submandibular saliva. Preliminary tests were carried out on saliva collected from a single donor in order to determine whether the rheological properties of submandibular saliva collected using the device were comparable to whole saliva collected using the expectoration (or 'spit') method. The device collected a lower quantity of saliva than that collected using the expectoration method. Stimulated saliva collected using the device had a pH close to that of unstimulated saliva because the sealed collection unit in the device minimised contamination. Saliva exhibited shear-thinning behaviour regardless of the method of collection, although that collected using the device was more viscous. The viscoelasticity of saliva collected using the two methods was different, probably as a result of differences in composition. This difference was greater with stimulated saliva. Despite the discrepancies between whole saliva and submandibular saliva, the device provides a non-invasive method for the collection of high-quality saliva over extended periods.

Determination of morphine, codeine and 6-monoacetylmorphine in saliva of substance-abuse patients using HPLC/MS methods

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Milovanović Vesna

2012-01-01

Full Text Available Background/Aim. Saliva represents an alternative specimen for substances abuse determination in toxicology. Hence, the aim of this study was to optimize a method for saliva specimen preparation for heroin metabolites, morphine and 6-monoacetylmorphine (6-mam, and codeine determination by liquid chromatography-mass spectrometry (LC/MS, and to apply this method on saliva samples taken from the patients. Methods. Saliva specimen was prepared using liqiud/liquid extraction of morphine, codeine and 6- mam by mixture of chloroform and isopropanol (9 : 1; v/v. Extracts were analysed by HPLC/MS technique: separation column Waters Spherisorb® 5 μm, ODS2, 4.6 × 100 mm; mobile phase: ammonium acetate : acetonitile (80 : 20; v/v, mobile phase flow rate 0.3 mL/min; mass detection range: 100-400 m/z. Regression and correlation analyses were performed with the probalility level of 0.05. Concentrations of morphine, codeine and 6-mam were determined in saliva samples of the patients with “opiates” in urine identified by the test strips. Results. Calibration for each analysed substance was done in the concentration range from 0.1 to 1 mg/L and the coefficient of correlation was R2 > 0.99. We obtained following calibration curves: y = 385531x + 14584; y = 398036x + 31542; and y = 524162x - 27105, for morphine, codeine and 6-mam, respectively. Recovery for morphine and codeine determination was 99%, while for 6- mam it was 94%. Limits of detection and quantification of a proposed method were 0.01 mg/L and 0.05 mg/L, respectively. Concentration of morphine in the saliva of the heroin users ranged between 0.54 and 5.82 mg/L, concentration of codeine between 0.05 and 5.33, and 6-mam between 0.01 and 0.68 mg/L. A statistically significant correlation between codeine and 6-mam concentrations was obtained. Conclusion. A proposed HPLC/MS method for morphine, codeine and 6-mam determination in saliva is accurate, simple, cheap and suitable for routine analysis and

Determination of carbamazepine in serum and saliva samples by high performance liquid chromatography with ultraviolet detection.

Science.gov (United States)

Dordević, Snezana; Kilibarda, Vesna; Stojanović, Tomislav

2009-05-01

Carbamazepine is antiepileptic drug widely used for the treatment of epilepsy. Due to low therapeutic index of carbamazepine there is a need for routine measuring its concentrations in biological fluids. The aim of the study was to describe a method for concomitant determination of carbamazepine in the serum and saliva. Separation of the drug from matrix is achieved by reversed-phase chromatography on a C18 column, with a mobile phase of methanol-water-acetic acid (65:34:1) at a flow-rate of 1.0 ml/min. Detection was effected by ultra-violet absorption at 285 nm. The total run time was 5 min. Samples were prepared by alkaline extraction (pH 10) using chlorophorm. Calibration curves were in the range 0.1-5 microg/mL for serum and saliva samples. Mean recoveries of spiked serum and saliva were 97.59 and 92.30%, respectively. Limits of detection (LOD) of carbamazepine in serum and saliva were 0.166 and 0.178 microg/mL, respectively. Limits of quantification (LOQ) in the serum and saliva were 0.237 and 0.226 microg/mL, respectively. The method precision was carried out with coefficient of variation of 2.10% and 4.03% for the serum and saliva, respectively. The obtained data showed that there was a strong correlation between saliva and serum concentrations (r = 0.9481, p < 0.001). The method described here is rapid, precise, accurate and simple, and can be used for quantitative determination of carbamazepine in human serum and saliva after therapy applying. Saliva samples could be used as an alternative matrix for therapeutic drug monitoring of this antiepileptic drug.

Degradation of Paracetamol by Photolysis Using C-N-codoped TiO2

OpenAIRE

Vanny Yulia Safitri; Adlis Santoni; Diana Vanda Wellia; Khoiriah Khoiriah; Safni Safni

2017-01-01

Paracetamol is generally used as analgesic and antipyretic drugs. Contamination paracetamol in the environment can occur because of waste material disposal from production site and immediate disposal of household that cause water pollution. Paracetamol is degraded by photolysis method under irradiation 10 watt UV-light (λ=365 nm), visible-light (Philips LED 13 watt 1400 lux) and solar-light with and without addition C-N-codoped TiO2catalyst. The solution is analyzed by UV-Vis spectrophotomete...

Oestrogens in saliva

International Nuclear Information System (INIS)

Rothschild, R.S.; Levine, L.S.; Hattingh, J.

1981-01-01

Matched plasma and saliva samples were obtained from a non-pregnant and pregnant group (last trimester) of female caucasians. Using a sensitive radioimmunoassay, 17β-oestradiol was measured, and the gingival index system of Loe (1967) was used to assess the gingival condition of each patient. The results showed that 17β-oestradiol could be measured in saliva but that the levels were extremely low and a very sensitive immunoassay was necessary. In the pregnant group, saliva represented 3 per cent of the plasma level. This was not the case in the non-pregnant group, probably because of the constantly changing free: bound plasma ratio. The results are discussed in relation to the fact that oestrogens are known to bind to the oral epithelium [af

Combined paracetamol and amitriptyline adsorption to activated charcoal

DEFF Research Database (Denmark)

Hoegberg, Lotte Christine Groth; Groenlykke, Thor Buch; Abildtrup, Ulla

2010-01-01

Objectives. High-gram drug doses seen in multiple-drug poisonings might be close to the adsorption capacity of activated charcoal (AC). The aim was to determine the maximum adsorption capacities (Q(m)) of amitriptyline and paracetamol, separately and in combination, to AC. Methods. ACs (Carbomix......® and Norit Ready-To-Use) were tested in vitro. At pH 1.2 and pH 7.2, 0.250 g AC and paracetamol and/or amitriptyline were mixed and incubated. The AC: drug ratios were 10:1, 5:1, 3:1, 2:1, and 1:1. The mixed-drug adsorption vials contained the same AC: paracetamol ratios, but amitriptyline was added as fixed...... Ready-To-Use. The tested pH differences had minor effect on the adsorption. The mixed-drug adsorption showed about 40% Q(m) reduction of each drug with increasing amounts of drug/g AC, but the total gram of drug adsorbed to AC was increased compared to one-drug conditions. Conclusion. The adsorption...

Magnetic molecularly imprinted polymer nanoparticles for the solid-phase extraction of paracetamole from plasma samples, followed its determination by HPLC

International Nuclear Information System (INIS)

Azodi-Deilami, Saman; Najafabadi, Alireza Hassani; Asadi, Ebadullah; Abdouss, Majid; Kordestani, Davood

2014-01-01

We are presenting magnetic molecularly imprinted polymer nanoparticles (m-MIPs) for solid-phase extraction and sample clean-up of paracetamole. The m-MIPs were prepared from magnetite (Fe 3 O 4 ) as the magnetic component, paracetamole as the template, methacrylic acid as a functional monomer, and 2-(methacrylamido) ethyl methacrylate as a cross-linker. The m-MIPs were then characterized by transmission electron microscopy, FT-IR spectroscopy, X-ray diffraction and vibrating sample magnetometry. The m-MIPs were applied to the extraction of paracetamole from human blood plasma samples. Following its elution from the column loaded with the m-MIPs with an acetonitrile-buffer (9:1) mixture, it was submitted to HPLC analysis. Paracetamole can be quantified by this method in the 1 μg L −1 to 300 μg L −1 concentration range. The limit of detection and limit of quantification in plasma samples are 0.17 and 0.4 μg L −1 . The preconcentration factor of the m-MIPs is 40. The HPLC method shows good precision (4.5 % at 50 μg L −1 levels) and recoveries (between 83 and 91 %) from spiked plasma samples. (author)

Staggered overdose pattern and delay to hospital presentation are associated with adverse outcomes following paracetamol-induced hepatotoxicity

Science.gov (United States)

Craig, Darren G N; Bates, Caroline M; Davidson, Janice S; Martin, Kirsty G; Hayes, Peter C; Simpson, Kenneth J

2012-01-01

AIMS Paracetamol (acetaminophen) poisoning remains the major cause of severe acute hepatotoxicity in the UK. In this large single centre cohort study we examined the clinical impact of staggered overdoses and delayed presentation following paracetamol overdose. RESULTS Between 1992 and 2008, 663 patients were admitted with paracetamol-induced severe liver injury, of whom 161 (24.3%) had taken a staggered overdose. Staggered overdose patients were significantly older and more likely to abuse alcohol than single time point overdose patients. Relief of pain (58.2%) was the commonest rationale for repeated supratherapeutic ingestion. Despite lower total ingested paracetamol doses and lower admission serum alanine aminotransferase concentrations, staggered overdose patients were more likely to be encephalopathic on admission, require renal replacement therapy or mechanical ventilation and had higher mortality rates compared with single time point overdoses (37.3% vs. 27.8%, P = 0.025), although this overdose pattern did not independently predict death. The King's College poor prognostic criteria had reduced sensitivity (77.6, 95% CI 70.8, 81.5) for this pattern of overdose. Of the 396/450 (88.0%) single time point overdoses in whom accurate timings could be obtained, 178 (44.9%) presented to medical services >24 h following overdose. Delayed presentation beyond 24 h post overdose was independently associated with death/liver transplantation (OR 2.25, 95% CI 1.23, 4.12, P = 0.009). CONCLUSIONS Both delayed presentation and staggered overdose pattern are associated with adverse outcomes following paracetamol overdose. These patients are at increased risk of developing multi-organ failure and should be considered for early transfer to specialist liver centres. PMID:22106945

Comparison of analgesic efficacy of intravenous Paracetamol and intravenous dexketoprofen trometamol in multimodal analgesia after hysterectomy

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Çiğdem Ünal

2013-01-01

Full Text Available Backround: We aimed to evaluate analgesic efficacy, opioid-sparing, and opioid-related adverse effects of intravenous paracetamol and intravenous dexketoprofen trometamol in combination with iv morphine after total abdominal hysterectomy. Materials and Methods: Sixty American Society of Anesthesiologist Physical Status Classification I-II patients scheduled for total abdominal hysterectomy were enrolled to this double-blinded, randomized, placebo controlled, and prospective study. Patients were divided into three groups as paracetamol, dexketoprofen trometamol, and placebo (0.9% NaCl due to their post-operative analgesic usage. Intravenous patient controlled analgesia morphine was used as a rescue analgesic in all groups. Pain scores, hemodynamic parameters, morphine consumption, patient satisfaction, and side-effects were evaluated. Results: Visual Analog Scale (VAS scores were not statistically significantly different among the groups in all evaluation times, but decrease in VAS scores was statistically significant after the evaluation at 12 th h in all groups. Total morphine consumption (morphine concentration = 0.2 mg/ml in group paracetamol (72.3 ± 38.0 ml and dexketoprofen trometamol (69.3 ± 24.1 ml was significantly lower than group placebo (129.3 ± 22.6 ml (P < 0.001. Global satisfaction scores of the patients in group placebo was significantly lower than group dexketoprofen trometamol after surgery and the increase in global satisfaction score was significant only in group placebo. Conclusion: Dexketoprofen trometamol and Paracetamol didn′t cause significant change on pain scores, but increased patients′ comfort. Although total morphine consumption was significantly decreased by both drugs, the incidence of nausea and vomiting were similar among the groups. According to results of the present study routine addition of dexketoprofen trometamol and paracetamol to patient controlled analgesia morphine after hysterectomies is not

REVIEW ARTICLE – Intravenous paracetamol in pediatrics: A global perspective

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Muzammil Irshad, MBBS

2012-12-01

Full Text Available Intravenous (IV Paracetamol is an excellent post operative analgesic and antipyretic in children. Efficacy and tolerability of IV Propacetamol have been established in pediatric practice. It is believed that paracetamol works by inhibiting cyclooxygenase-2 (COX-2 enzymes. Studies bring to light that therapeutic doses of IV acetaminophen are effective and tolerable in children with least chances of hepatotoxicity. However, overdose toxicity has been reported in children and drug induced hypotension in febrile critically ill patients. Therapeutic doses according to body weight of neonates and children can be administered in hospital settings. Special education of health care staff regarding precise dose and solution is necessary to assess the role of IV paracetamol preparation in pediatric practice.

Estimation of Cutoff Values of Cotinine in Urine and Saliva for Pregnant Women in Poland

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Joanna Stragierowicz

2013-01-01

Full Text Available Setting appropriate cutoff values and the use of a highly sensitive analytical method allow for correct classification of the smoking status. Urine-saliva pairs samples of pregnant women in the second and third trimester, and saliva only in the first trimester were collected. Offline SPE and LC-ESI-MS/MS method was developed in the broad concentration range (saliva 0.4–1000 ng/mL, urine 0.8–4000 ng/mL. The mean recoveries were 3.7±7.6% for urine and 99.1±2.6% for saliva. LOD for saliva was 0.12 ng/mL and for urine 0.05 ng/mL; LOQ was 0.4 ng/mL and 0.8 ng/mL, respectively. Intraday and interday precision equaled, respectively, 1.2% and 3.4% for urine, and 2.3% and 6.4% for saliva. There was a strong correlation between salivary cotinine and the uncorrected cotinine concentration in urine in the second and third trimesters of pregnancy. The cutoff values were established for saliva 12.9 ng/mL and urine 42.3 ng/mL or 53.1 μg/g creatinine with the ROC curve analysis. The developed analytical method was successfully applied to quantify cotinine, and a significant correlation between the urinary and salivary cotinine levels was found. The presented cut-off values for salivary and urinary cotinine ensure a categorization of the smoking status among pregnant women that is more accurate than self-reporting.

Increase in salivary cysteinyl-leukotriene concentration in patients with aspirin-intolerant asthma.

Science.gov (United States)

Ono, Emiko; Taniguchi, Masami; Higashi, Noritaka; Mita, Haruhisa; Yamaguchi, Hiromichi; Tatsuno, Sayaka; Fukutomi, Yuma; Tanimoto, Hidenori; Sekiya, Kiyoshi; Oshikata, Chiyako; Tsuburai, Takahiro; Tsurikisawa, Naomi; Otomo, Mamoru; Maeda, Yuji; Hasegawa, Maki; Miyazaki, Eishi; Kumamoto, Toshihide; Akiyama, Kazuo

2011-03-01

Cysteinyl-leukotrienes (CysLTs; LTC4, LTD4, and LTE4) play a considerable role in the pathophysiology of aspirin-intolerant asthma (AIA). Saliva has recently been validated as novel, simple, and noninvasive method for investigating inflammation in patients with asthma. The aim of this study is to clarify the molecular species of CysLT in saliva and to evaluate the CysLT and LTB4 concentrations in saliva in AIA patients. We also examined how the CysLT concentration in saliva reflects that of their corresponding urinary metabolite. We preformed an analytical cross-sectional study. CysLT and LTB4 concentrations in saliva were quantified by enzyme immunoassay (EIA) following purification by high-performance liquid chromatography (HPLC). 1. When analyzed by EIA in combination with HPLC, saliva was found to consist of LTC4, LTD4 and LTE4 in similar amounts. 2. In saliva analysis among the three groups (AIA patients, aspirin-tolerant asthma [ATA] patients, and healthy subjects), both the concentrations of CysLTs and LTB4 were significantly higher in AIA patients than in ATA patients and healthy subjects. 3. We found significant correlations between CysLT concentration and LTB4 concentration in saliva in each group. 4. No significant correlation was found between the concentration of LTE4 in urine and that of CysLTs in saliva. In this study, we found higher concentrations of CysLTs and LTB4 in saliva from AIA patients than in saliva from ATA patients, suggesting that the quantification of CysLT and LTB4 concentrations in saliva may be another diagnostic strategy for AIA.

ARSENIC SPECIATION ANALYSIS IN HUMAN SALIVA

Science.gov (United States)

Background: Determination of arsenic species in human saliva is potentially useful for biomonitoring of human exposure to arsenic and for studying arsenic metabolism. However, there is no report on the speciation analysis of arsenic in saliva. Methods: Arsenic species in saliva ...

Paracetamol for pain relief after surgical removal of lower wisdom teeth

NARCIS (Netherlands)

Weil, K.; Hooper, L.; Afzal, Z.; Esposito, M.; Worthington, H.V.; van Wijk, A.J.; Coulthard, P.

2008-01-01

Background: Paracetamol has been commonly used for the relief of postoperative pain following oral surgery. In this review we investigated the optimal dose of paracetamol and the optimal time for drug administration to provide pain relief, taking into account the side effects of different doses of

Neonatal Maturation of Paracetamol (Acetaminophen) Glucuronidation, Sulfation, and Oxidation Based on a Parent-Metabolite Population Pharmacokinetic Model.

Science.gov (United States)

Cook, Sarah F; Stockmann, Chris; Samiee-Zafarghandy, Samira; King, Amber D; Deutsch, Nina; Williams, Elaine F; Wilkins, Diana G; Sherwin, Catherine M T; van den Anker, John N

2016-11-01

This study aimed to model the population pharmacokinetics of intravenous paracetamol and its major metabolites in neonates and to identify influential patient characteristics, especially those affecting the formation clearance (CL formation ) of oxidative pathway metabolites. Neonates with a clinical indication for intravenous analgesia received five 15-mg/kg doses of paracetamol at 12-h intervals (paracetamol, paracetamol-glucuronide, paracetamol-sulfate, and the combined oxidative pathway metabolites (paracetamol-cysteine and paracetamol-N-acetylcysteine) were simultaneously modeled in NONMEM 7.2. The model incorporated 259 plasma and 350 urine samples from 35 neonates with a mean gestational age of 33.6 weeks (standard deviation 6.6). CL formation for all metabolites increased with weight; CL formation for glucuronidation and oxidation also increased with postnatal age. At the mean weight (2.3 kg) and postnatal age (7.5 days), CL formation estimates (bootstrap 95% confidence interval; between-subject variability) were 0.049 L/h (0.038-0.062; 62 %) for glucuronidation, 0.21 L/h (0.17-0.24; 33 %) for sulfation, and 0.058 L/h (0.044-0.078; 72 %) for oxidation. Expression of individual oxidation CL formation as a fraction of total individual paracetamol clearance showed that, on average, fractional oxidation CL formation increased paracetamol and its metabolites in neonates. Maturational changes in the fraction of paracetamol undergoing oxidation were small relative to between-subject variability.

Does cytochrome P450 liver isoenzyme induction increase the risk of liver toxicity after paracetamol overdose?

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Kalsi SS

2011-10-01

Full Text Available Sarbjeet S Kalsi1,2, David M Wood2–4, W Stephen Waring5, Paul I Dargan2–4 1Emergency Department, 2Clinical Toxicology, Guy's and St Thomas' NHS Foundation Trust, London; 3King's Health Partners, 4King's College London, London; 5York Teaching Hospital NHS Foundation Trust, York, UK Abstract: Paracetamol (acetaminophen, N-acetyl-p-aminophenol, 4-hydroxyacetanilide is the most common cause of acute liver failure in developed countries. There are a number of factors which potentially impact on the risk of an individual developing hepatotoxicity following an acute paracetamol overdose. These include the dose of paracetamol ingested, time to presentation, decreased liver glutathione, and induction of cytochrome P450 (CYP isoenzymes responsible for the metabolism of paracetamol to its toxic metabolite N-acetyl-p-benzoquinoneimine (NAPQI. In this paper, we review the currently published literature to determine whether induction of relevant CYP isoenzymes is a risk factor for hepatotoxicity in patients with acute paracetamol overdose. Animal and human in vitro studies have shown that the CYP isoenzyme responsible for the majority of human biotransformation of paracetamol to NAPQI is CYP2E1 at both therapeutic and toxic doses of paracetamol. Current UK treatment guidelines suggest that patients who use a number of drugs therapeutically should be treated as “high-risk” after paracetamol overdose. However, based on our review of the available literature, it appears that the only drugs for which there is evidence of the potential for an increased risk of hepatotoxicity associated with paracetamol overdose are phenobarbital, primidone, isoniazid, and perhaps St John's wort. There is no evidence that other drugs often quoted as increasing risk, such as carbamazepine, phenytoin, primidone, rifampicin, rifabutin, efavirenz, or nevirapine, should be considered risk factors for hepatotoxicity in patients presenting with acute paracetamol overdose. Keywords

The pH changes of artificial saliva after interaction with oral of artificial saliva after interaction with oral micropathogen

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Basri A. Gani

2012-12-01

Full Text Available Backgorund: Saliva contains several protein elements, exocrine proteins and antibodies, such as lactoferrin, sIgA, peroxidase, albumin, polypeptides, and oligopeptides that contribute to the defense of oral mucosa and dental pellicle to prevent infection caused by oral micropathogen, such as Candida albicans, Streptococcus mutans and Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans. Those micropathogens have a role to change salivary pH as an indicator of oral disease activities. Purpose: This study was aimed to analyze the changes of artificial saliva pH after interaction with S. mutans, C. albicans, and A. Actinomycetemcpmitans. Methods: The materials used in this study consist of S. mutans (ATCC 31987, C. albicans (ATCC 10231, A. actinomycetemcomitans (ATTC 702 358, and artificial saliva. To examine the pH changes of artificial saliva, those three microbiotas were cultured and incubated for 24 hours. Results: The results showed that the interactions of S. mutans, C. albicans, and A. actinomycetemcomitans in the artificial saliva can change the salivary on neutral. There were no significant difference with the control treatment salivary pH 4, 5, 6, 8, and 9 (p>0.05. Similarly, there was also no significant difference when those three microorganism interacted each other in the artificial saliva (p<0.05. Conclusion: It can be concluded that the biological activity of S. mutans, C. albicans, and A. actinomycetemcomitans in artificial saliva can change the salivary pH into neutral. It indicates that those microbiotas mutually supported and cooperated in influencing the biological cycle of the oral cavity with salivary pH as an indicator.Latar belakang: Saliva merupakan cairan eksokrin yang mengandung unsur protein dan antibodi seperti sIgA laktoferin peroksidase, albumin, polipeptida dan oligopeptida yang berperan pada pertahanan mukosa rongga mulut dan gigi guna mencegah infeksi oral mikropatogen seperti C. albicans, S. mutans, dan

Determination of carbamazepine in serum and saliva samples by high performance liquid chromatography with ultraviolet detection

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Đorđević Snežana

2009-01-01

Full Text Available Background/Aim. Carbamazepine is antiepileptic drug widely used for the treatment of epilepsy. Due to low therapeutic index of carbamazepine there is a need for routine measuring its concentrations in biological fluids. The aim of the study was to describe a method for concomitant determination of carbamazepine in the serum and saliva. Methods. Separation of the drug from matrix is achieved by reversedphase chromatography on a C18 column, with a mobile phase of methanol-water-acetic acid (65:34:1 at a flow-rate of 1.0 ml/min. Detection was effected by ultra-violet absorption at 285 nm. The total run time was 5 min. Samples were prepared by alkaline extraction (pH 10 using chlorophorm. Results. Calibration curves were in the range 0.1-5 μg/mL for serum and saliva samples. Mean recoveries of spiked serum and saliva were 97.59 and 92.30%, respectively. Limits of detection (LOD of carbamazepine in serum and saliva were 0.166 and 0.178 μg/mL, respectively. Limits of quantification (LOQ in the serum and saliva were 0.237 and 0.226 μg/mL, respectively. The method precision was carried out with coefficient of variation of 2.10% and 4.03% for the serum and saliva, respectively. The obtained data showed that there was a strong correlation between saliva and serum concentrations (r = 0.9481, p < 0.001. Conclusion. The method described here is rapid, precise, accurate and simple, and can be used for quantitative determination of carbamazepine in human serum and saliva after therapy applying. Saliva samples could be used as an alternative matrix for therapeutic drug monitoring of this antiepileptic drug.

Analgesic activity of fixed dose combinations of paracetamol with diclofenac sodium and paracetamol with tramadol on different pain models in healthy volunteers - A randomized double blind crossover study

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Sachidanand Tripathi

2012-01-01

Conclusion: Paracetamol with tramadol combination was more effective than paracetamol with diclofenac sodium combination on the radiant heat model. In human pain models, there is an incomplete understanding of mechanisms and activated pathways are not precisely determined that needs further evaluation.

Lutzomyia longipalpis saliva or salivary protein LJM19 protects against Leishmania braziliensis and the saliva of its vector, Lutzomyia intermedia.

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Natalia M Tavares

Full Text Available BACKGROUND: Leishmania transmission occurs in the presence of insect saliva. Immunity to Phlebotomus papatasi or Lutzomyia longipalpis saliva or salivary components confers protection against an infection by Leishmania in the presence of the homologous saliva. However, immunization with Lutzomyia intermedia saliva did not protect mice against Leishmania braziliensis plus Lu. intermedia saliva. In the present study, we have studied whether the immunization with Lu. longipalpis saliva or a DNA plasmid coding for LJM19 salivary protein would be protective against L. braziliensis infection in the presence of Lu. intermedia saliva, the natural vector for L. braziliensis. METHODOLOGY/PRINCIPAL FINDINGS: Immunization with Lu. longipalpis saliva or with LJM19 DNA plasmid induced a Delayed-Type Hypersensitivity (DTH response against Lu. longipalpis as well as against a Lu. intermedia saliva challenge. Immunized and unimmunized control hamsters were then intradermally infected in the ears with L. braziliensis in the presence of Lu. longipalpis or Lu. intermedia saliva. Animals immunized with Lu. longipalpis saliva exhibited smaller lesion sizes as well as reduced disease burdens both at lesion site and in the draining lymph nodes. These alterations were associated with a significant decrease in the expression levels of IL-10 and TGF-β. Animals immunized with LJM19 DNA plasmid presented similar findings in protection and immune response and additionally increased IFN-γ expression. CONCLUSIONS/SIGNIFICANCE: Immunization with Lu. longipalpis saliva or with a DNA plasmid coding LJM19 salivary protein induced protection in hamsters challenged with L. braziliensis plus Lu. intermedia saliva. These findings point out an important role of immune response against saliva components, suggesting the possibility to develop a vaccine using a single component of Lu. longipalpis saliva to generate protection against different species of Leishmania, even those

Disposition of Lead (Pb) in Saliva and Blood of Sprague-Dawley Rats Following a Single or Repeated Oral Exposure to Pb-Acetate

Energy Technology Data Exchange (ETDEWEB)

Timchalk, Chuck; Lin, Yuehe; Weitz, Karl K.; Wu, Hong; Gies, Richard A.; Moore, Dean A.; Yantasee, Wassana

2006-05-01

Biological monitoring for lead (Pb) is usually based upon a determination of blood Pb concentration; however, saliva has been suggested as a non-invasive biological matrix for assessing exposure. To further evaluate the potential utility of saliva for biomonitoring, the disposition of Pb was evaluated in whole blood (WB), red blood cells (RBC), plasma, parotid gland, bone, and saliva following either a single oral dose of 100 mg Pb-acetate/kg body weight in rats or {approx}1-week after 5 sequential daily oral gavage doses of 1, 10, or 100 mg Pb-acetate/kg/day. Saliva volume, pH, total saliva protein, and ?-amylase activity were also determined. At specified times post-dosing groups of animals were anethetized and administered pilocarpine to induce salivation. Saliva was collected, the animals were humanely sacrificed, and tissue samples were likewise collected, weighed, and processed for Pb analysis. Following a single dose exposure to PB-acetate, Pb was detectable in all samples by 30 min post-dosing. For both the single and repeated dose treatments the concentration of Pb was highest in WB and RBC relative to plasma and saliva. However, the Pb rapidly redistributed (within 5-days post-treatment) from the blood into the bone compartment based on the substantial decrease in WB and RBC Pb concentration, and the concurrent increase in bone Pb following repeated exposure at all dose levels. Although there is clear variability in the observed Pb concentrations in plasma and saliva, there was a reasonable correlation (r2=0.922) between the average Pb concentrations in these biological matrices which was consistent with previous observations. The single oral dose of Pb-acetate resulted in a decrease in salivary pH which recovered by 24 hr post-dosing and a decrease in ?-amylase enzyme activity which did recover within 5-days of ceasing exposure. It is currently unclear what impact these slight functional changes may or may not have on Pb salivary clearance rates. These

Isolation and Analytical Characterization of Local Malaysian Leech Saliva

Directory of Open Access Journals (Sweden)

Mohamed Alaama

2011-12-01

Full Text Available Leech saliva contains biologically active compounds that are mainly proteins and peptides. In this study a modified and smooth extraction method of saliva was used without leeches' scarification. UV and Bradford Assay protein methods showed that the saliva extract contains high concentrations of proteins. RP-HPLC chromatogram revealed that more than 30 different peaks were observed in leech saliva extract. Gel electrophoresis revealed the existence of proteins and peptides with different molecular weights. The gel showed up to 25 different bands. Comparison of gel electrophoresis data with protein database revealed the closeness of four molecular weights to known proteins from Hirudinaria leech family. Other proteins detected by gel electrophoresis may be related to completely new biologically active proteins and peptides in the saliva extract or to a modification (isoforms of the existing ones or finally to a mixture of both.ABSTRAK: Air liur pacat secara biologinya mengandungi sebahagian besar campuran aktif protein dan peptida. Dalam kajian ini, kaedah pengestrakan air liur pacat yang telah diubah suai digunakan tanpa perlu membunuh pacat. Kaedah protein Cerakin UV dan Bradford menunjukkan air liur pacat yang diekstrak mengandungi konsentrasi protein yang tinggi. Kromatogram RP-HPLC memperlihatkan lebih daripada 30 puncak berbeza diperolehi semasa air liur pacat diekstrak. Gel elektroforesis memperlihatkan kewujudan protein dan peptida dengan berat molekul yang berbeza. Gel menunjukkan hingga 25 jalur yang berbeza. Perbandingan data menggunakan gel elektroforesis seiring dengan pangkalan data protein memperlihatkan persamaan empat berat molekul, dengan protein yang yang dikenali daripada keluarga pacat Hirudinaria. Jenis protein lain yang dikesan dengan menggunakan gel elektrofosis mungkin juga berkait secara biologinya dengan protein dan peptida aktif yang baru, dalam ekstrak air liur atau pengubahsuaian (beberapa jenis yang berbeza daripada

Long-term prognosis for transplant-free survivors of paracetamol-induced acute liver failure

DEFF Research Database (Denmark)

Jepsen, P; Schmidt, L E; Larsen, F S

2010-01-01

The prognosis for transplant-free survivors of paracetamol-induced acute liver failure remains unknown.......The prognosis for transplant-free survivors of paracetamol-induced acute liver failure remains unknown....

Paracetamol (acetaminophen) for chronic non-cancer pain in children and adolescents.

Science.gov (United States)

Cooper, Tess E; Fisher, Emma; Anderson, Brian; Wilkinson, Nick Mr; Williams, David G; Eccleston, Christopher

2017-08-02

Pain is a common feature of childhood and adolescence around the world, and for many young people, that pain is chronic. The World Health Organization guidelines for pharmacological treatments for children's persisting pain acknowledge that pain in children is a major public health concern of high significance in most parts of the world. While in the past, pain was largely dismissed and was frequently left untreated, views on children's pain have changed over time, and relief of pain is now seen as important.We designed a suite of seven reviews on chronic non-cancer pain and cancer pain (looking at antidepressants, antiepileptic drugs, non-steroidal anti-inflammatory drugs, opioids, and paracetamol as priority areas) in order to review the evidence for children's pain utilising pharmacological interventions in children and adolescents.As the leading cause of morbidity in children and adolescents in the world today, chronic disease (and its associated pain) is a major health concern. Chronic pain (lasting three months or longer) can arise in the paediatric population in a variety of pathophysiological classifications: nociceptive, neuropathic, idiopathic, visceral, nerve damage pain, chronic musculoskeletal pain, and chronic abdominal pain, and other unknown reasons.Paracetamol (acetaminophen) is one of the most widely used analgesics in both adults and children. The recommended dosage in the UK, Europe, Australia, and the USA for children and adolescents is generally 10 to 15 mg/kg every four to six hours, with specific age ranges from 60 mg (6 to 12 months old) up to 500 to 1000 mg (over 12 years old). Paracetamol is the only recommended analgesic for children under 3 months of age. Paracetamol has been proven to be safe in appropriate and controlled dosages, however potential adverse effects of paracetamol if overdosed or overused in children include liver and kidney failure. To assess the analgesic efficacy and adverse events of paracetamol (acetaminophen) used

Effect of paracetamol injection on the analgesic effect of tramadol in ...

African Journals Online (AJOL)

Five dogs each were randomly treated with 30mg/kg paracetamol (treatment KXDTA) intravenously or equal volume of normal saline (treatment KXDTS) to evaluate if paracetamol potentiate the analgesic effects of tramadol during the intra-operative period. Thirty minutes later, both groups were treated with 3mg/kg tramadol ...

Safety of Oral Paracetamol – Analysis of Data from a Spontaneous ...

African Journals Online (AJOL)

Purpose: To determine the safety of oral coated paracetamol tablets 500 mg and oral suspension 120 mg/5 mL produced by Hasco-Lek Poland. Methods: We analyzed sales volume and data obtained from the monitoring of spontaneous reports on the adverse effects of paracetamol collected in the period between ...

[Intentional paracetamol intoxication in children

NARCIS (Netherlands)

Bisschops, L.L.; Bisschops, W.A.; Vroegop, M.P.; Rossum, L.K. van; Kramers, C.

2011-01-01

As paracetamol is widely used and easily available acetaminophen auto-intoxication is frequently seen. In the majority of patients no complications will occur, but in a small group it may lead to liver damage and death. Children are less susceptible to complications than adults. Cornerstone of

Application of Response Surface Methodology for Optimization of Paracetamol Particles Formation by RESS Method

International Nuclear Information System (INIS)

Sabet, J.K.; Ghotbi, C.; Dorkoosh, F.

2012-01-01

Ultrafine particles of paracetamol were produced by Rapid Expansion of Supercritical Solution (RESS). The experiments were conducted to investigate the effects of extraction temperature (313-353 K), extraction pressure (10-18 MPa), pre expansion temperature (363-403 K), and post expansion temperature (273-323 K) on particles size and morphology of paracetamol particles. The characterization of the particles was determined by Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), and Liquid Chromatography/Mass Spectrometry (LC-MS) analysis. The average particle size of the original paracetamol was 20.8 μm, while the average particle size of paracetamol after nan onization via the RESS process was 0.46 μm depending on the experimental conditions used. Moreover, the morphology of the processed particles changed to spherical and regular while the virgin particles of paracetamol were needle-shape and irregular. Response surface methodology (RSM) was used to optimize the process parameters. The extraction temperature, 347 K; extraction pressure, 12 MPa; pre expansion temperature, 403?K; and post expansion temperature, 322 K was found to be the optimum conditions to achieve the minimum average particle size of paracetamol.

Scalp hair and saliva as biomarkers in determination of mercury levels in Iranian women: Amalgam as a determinant of exposure

Energy Technology Data Exchange (ETDEWEB)

Fakour, H., E-mail: fakour.h@gmail.com [Department of Environment, Faculty of Natural Resources and Marine Sciences, Tarbiat Modares University, Noor, Mazandaran (Iran, Islamic Republic of); Esmaili-Sari, A. [Department of Environment, Faculty of Natural Resources and Marine Sciences, Tarbiat Modares University, Noor, Mazandaran (Iran, Islamic Republic of); Zayeri, F. [Department of Biostatistics, Faculty of Paramedical Sciences and Proteomics Research Center, Shahid Beheshti University of Medical Sciences, Tehran (Iran, Islamic Republic of)

2010-05-15

The aim of this study was to determine the relationship between mercury concentrations in saliva and hair in women with amalgam fillings and its relation with age and number of amalgam fillings. Eighty-two hair and saliva samples were collected randomly from Iranian women who have the same fish consumption pattern and free from occupational exposures. The mean {+-} SD age of these women was 29.37 {+-} 8.12 (ranged from 20 to 56). The determination of Hg level in hair samples was carried out by the LECO, AMA 254, Advanced Mercury Analyzer according to ASTM, standard No. D-6722. Mercury concentration in saliva samples was analyzed by PERKIN-ELMER 3030 Cold Vapor Atomic Absorption Spectrophotometer. The mean {+-} SD mercury level in the women was 1.28 {+-} 1.38 {mu}g/g in hair and 4.14 {+-} 4.08 {mu}g/l in saliva; and there were positive correlation among them. A significant correlation was also observed between Hg level of saliva (Spearman's {rho} = 0.93, P < 0.001) and hair (Spearman's {rho} = 0.92, P < 0.001) with number of amalgam fillings. According to the results, we can conclude that amalgam fillings may be an effective source for high Hg concentration in hair and releasing the mercury to the saliva samples.

Paracetamol. Ny viden om virkningsmekanismer samt smertelindrende og antiinflammatorisk effekt sammenlignet med ikke-steroide antiinflammatorika

DEFF Research Database (Denmark)

Handberg, G

2000-01-01

Paracetamol is usually termed a peripheral analgesic from the common belief that its site of action is near the injury. In this review a possible central action is summarised. Furthermore the analgesic effect of paracetamol is compared to non-steroidal anti-inflammatory drugs and the possible anti......-inflammatory effect of paracetamol is discussed....

Oral fixed drug combination analgesic tramadol/paracetamol: Benefits for patients and budgets

NARCIS (Netherlands)

M.J.C. Nuijten (Mark); B.P. Nautrup (Barbara Poulsen); H. Liedgens (Hiltrud)

2006-01-01

textabstractAlthough pain can present in many different ways, acute, subacute and chronic pain are frequently used and helpful categories that cover a wide range of pain phenomena. This paper reviews five cost-minimization studies of tramadol/paracetamol compared with codeine/paracetamol,

A study of the changes during heating of paracetamol.

Science.gov (United States)

de Wet, F N; Gerber, J J; Lötter, A P; van der Watt, J G; Dekker, T G

1998-05-01

The orthorhombic form of paracetamol has been shown to exhibit greater compressibility and faster dissolution than the monoclinic form. The orthorhombic form is produced by melting of monoclinic crystals of paracetamol followed by cooling at specific rates. Cooling rate, although a very important factor, is not the only factor influencing the formation of either of the two morphs. To study the cooling rate required for production of form II, paracetamol samples were melted in a differential scanning calorimeter, cooled at three specific rates, and melted again. In all of the samples, cooling resulted in the glassy form followed by recrystallization and the melting of form II. On the hot-stage microscope both forms were produced in one sample. Standardizing conditions for prediction of the resulting form remains a problem. There seems to be a great deal of overlap of the two forms' transition phases, which would make it difficult to force the crystallization of one form by keeping the solution or melt at a specific temperature. The thermal behavior of paracetamol during the heating and cooling phases must be understood in order to manipulate the process. A video camera mounted on a hot-stage microscope was used to follow the changes during heating and cooling of both forms. Nucleation, crystal growth, habit transformation, sublimation, and the final melt are shown on snap shots taken from the video.

Radiolytic degradation of paracetamol in dilute aqueous solution

International Nuclear Information System (INIS)

Szabo, L.; Toth, T.; Homlok, R.; Takacs, E.; Wojnarovits, L.

2011-01-01

Complete text of publication follows. Paracetamol or with name acetaminophen is widely used as analgesic and antipyretic drug. Due to its heavy use it is regularly detected in the surface waters. The degradation of the compound formerly was studied in several advanced oxidation processes (UV/H 2 O 2 , UV/TiO 2 , electrochemical oxidation, ozonation). Here we report on the radiolytic degradation. In the experimental work we combined a wide variety of techniques. For the investigation of the intermediates pulse radiolysis, for end-product experiments (decolouration, mineralization) gamma irradiation were used together with UV-Vis spectroscopy, HPLC separation (with diode array and MS-MS detection), chemical oxygen demand, total organic carbon content and toxicity measurements. · OH radicals are the main oxidative species during irradiation. They add to the aromatic ring producing hydroxycyclohexadienyl type radicals. These radicals either transform to hydroxy-paracetamol stable products in several reaction steps, or after water elimination transform to semi-iminoquinone radical. The reaction of hydroxycyclohexadienyl radicals with O 2 yields peroxi radicals. The latter radicals may eliminate HO 2 · or undergo ring opening and transformation, first to different carboxylic acids, and finally (mineralization) to CO 2 , H 2 O and NH 3 or NO 2 . Paracetamol has a relatively low toxicity. In 10 -3 mol dm -3 DCF solution after irradiation some products (e.g. hydroquinone, acetamide) are more toxic than paracetamol. By increasing the dose the toxicity suddenly decreases. It seems that the toxic products are highly sensitive to irradiation treatment.

High-pressure high-temperature phase diagram of organic crystal paracetamol

Science.gov (United States)

Smith, Spencer J.; Montgomery, Jeffrey M.; Vohra, Yogesh K.

2016-01-01

High-pressure high-temperature (HPHT) Raman spectroscopy studies have been performed on the organic crystal paracetamol in a diamond anvil cell utilizing boron-doped heating diamond anvil. Isobaric measurements were conducted at pressures up to 8.5 GPa and temperature up to 520 K in five different experiments. Solid state phase transitions from monoclinic Form I  →  orthorhombic Form II were observed at various pressures and temperatures as well as transitions from Form II  →  unknown Form IV. The melting temperature for paracetamol was observed to increase with increasing pressures to 8.5 GPa. This new data is combined with previous ambient temperature high-pressure Raman and x-ray diffraction data to create the first HPHT phase diagram of paracetamol.

High-pressure high-temperature phase diagram of organic crystal paracetamol

International Nuclear Information System (INIS)

Smith, Spencer J; Montgomery, Jeffrey M; Vohra, Yogesh K

2016-01-01

High-pressure high-temperature (HPHT) Raman spectroscopy studies have been performed on the organic crystal paracetamol in a diamond anvil cell utilizing boron-doped heating diamond anvil. Isobaric measurements were conducted at pressures up to 8.5 GPa and temperature up to 520 K in five different experiments. Solid state phase transitions from monoclinic Form I  →  orthorhombic Form II were observed at various pressures and temperatures as well as transitions from Form II  →  unknown Form IV. The melting temperature for paracetamol was observed to increase with increasing pressures to 8.5 GPa. This new data is combined with previous ambient temperature high-pressure Raman and x-ray diffraction data to create the first HPHT phase diagram of paracetamol. (paper)

Investigation of mixed saliva by optoelectronic methods

Science.gov (United States)

Savchenko, Ekaterina; Nepomnyashchaya, Elina; Baranov, Maksim; Velichko, Elena; Aksenov, Evgenii; Bogomaz, Tatyana

2018-04-01

At present, saliva and its properties are being actively studied. Human saliva is a unique biological material that has potential in clinical practice. A detailed analysis of the characteristics and properties of saliva is relevant for diagnostic purposes. In this paper, the properties and characteristics of saliva are studied using optoelectronic methods: dynamic light scattering, electrophoretic light scattering and optical microscopy. Mixed saliva from a healthy patient and patient with diabetes mellitus type 2 was used as an object of the study. The dynamics of the behavior of a healthy and patient with diabetes mellitus type 2 is visible according to the results obtained. All three methods confirm hypothesis of structural changes in mixed saliva in the disease of diabetes mellitus type 2.

Conformational and vibrational reassessment of solid paracetamol

Science.gov (United States)

Amado, Ana M.; Azevedo, Celeste; Ribeiro-Claro, Paulo J. A.

2017-08-01

This work provides an answer to the urge for a more detailed and accurate knowledge of the vibrational spectrum of the widely used analgesic/antipyretic drug commonly known as paracetamol. A comprehensive spectroscopic analysis - including infrared, Raman, and inelastic neutron scattering (INS) - is combined with a computational approach which takes account for the effects of intermolecular interactions in the solid state. This allows a full reassessment of the vibrational assignments for Paracetamol, thus preventing the propagation of incorrect data analysis and misassignments already found in the literature. In particular, the vibrational modes involving the hydrogen-bonded Nsbnd H and Osbnd H groups are correctly reallocated to bands shifted by up to 300 cm- 1 relatively to previous assignments.

Rapid determination of natural steroidal hormones in saliva for the clinical diagnoses

Directory of Open Access Journals (Sweden)

Oh Jin-Aa

2012-03-01

Full Text Available Abstract Background Saliva samples are easily collectable and non-invasive, and the monitoring of natural steroidal hormones, such as estrone (E1, 17β-estradiol (E2, estriol (E3, progesterone (P, and testosterone (T, in saliva has attracted much attention due to its numerous potential clinical and health-related applications. Because E1, E2, E3, P and T are useful indicators in numerous clinical and health-related diagnoses, there is a need for simultaneous determination. Results A gas chromatography-mass spectrometric assay was developed for rapid simultaneous determination of E1, E2, E3, P and T in saliva for clinical diagnoses. Extraction was achieved with a liquid extraction using 3.0 mL of pentane. The extract was dried and silylated with N-methyl-N-(trimethylsilyl trifluoroacetamide/NH4I (100:2 under a catalysis of 1.5% dithioerythritol for 10 min at 90°C. The accuracy of the analytes was in the range of 96% to 112% at concentrations of 0.05 and 0.10 μg/L (5.0 and 10.0 μg/L for E3, respectively, with relative standard deviations of less than 11%. The lowest quantification limits were from 0.002 to 0.6 μg/L for 1.0 mL of saliva. Conclusion Natural steroidal hormones were detected in the concentration ranges of nd to 0.2 μg/L in human saliva. The salivary testosterone values in the patients with prostatic carcinoma were significantly lower than in normal males. The method may useful in numerous clinical and health-related diagnoses.

A New Method for Noninvasive Genetic Sampling of Saliva in Ecological Research.

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Diana Lobo

Full Text Available Noninvasive samples for genetic analyses have become essential to address ecological questions. Popular noninvasive samples such as faeces contain degraded DNA which may compromise genotyping success. Saliva is an excellent alternative DNA source but scarcity of suitable collection methods makes its use anecdotal in field ecological studies. We develop a noninvasive method of collection that combines baits and porous materials able to capture saliva. We report its potential in optimal conditions, using confined dogs and collecting saliva early after deposition. DNA concentration in saliva extracts was generally high (mean 14 ng μl(-1. We correctly identified individuals in 78% of samples conservatively using ten microsatellite loci, and 90% of samples using only eight loci. Consensus genotypes closely matched reference genotypes obtained from hair DNA (99% of identification successes and 91% of failures. Mean genotyping effort needed for identification using ten loci was 2.2 replicates. Genotyping errors occurred at a very low frequency (allelic dropout: 2.3%; false alleles: 1.5%. Individual identification success increased with duration of substrate handling inside dog's mouth and the volume of saliva collected. Low identification success was associated with baits rich in DNA-oxidant polyphenols and DNA concentrations <1 ng μl(-1. The procedure performed at least as well as other noninvasive methods, and could advantageously allow detection of socially low-ranked individuals underrepresented in sources of DNA that are involved in marking behaviour (faeces or urine. Once adapted and refined, there is promise for this technique to allow potentially high rates of individual identification in ecological field studies requiring noninvasive sampling of wild vertebrates.

Enhancement of Cellulose Degradation by Cattle Saliva

Science.gov (United States)

Seki, Yasutaka; Kikuchi, Yukiko; Kimura, Yoshihiro; Yoshimoto, Ryo; Takahashi, Masatoshi; Aburai, Kenichi; Kanai, Yoshihiro; Ruike, Tatsushi; Iwabata, Kazuki; Sugawara, Fumio; Sakai, Hideki; Abe, Masahiko; Sakaguchi, Kengo

2015-01-01

Saccharification of cellulose is a promising technique for producing alternative source of energy. However, the efficiency of conversion of cellulose into soluble sugar using any currently available methodology is too low for industrial application. Many additives, such as surfactants, have been shown to enhance the efficiency of cellulose-to-sugar conversion. In this study, we have examined first whether cattle saliva, as an additive, would enhance the cellulase-catalyzed hydrolysis of cellulose, and subsequently elucidated the mechanism by which cattle saliva enhanced this conversion. Although cattle saliva, by itself, did not degrade cellulose, it enhanced the cellulase-catalyzed degradation of cellulose. Thus, the amount of reducing sugar produced increased approximately 2.9-fold by the addition of cattle saliva. We also found that non-enzymatic proteins, which were present in cattle saliva, were responsible for causing the enhancement effect. Third, the mechanism of cattle saliva mediated enhancement of cellulase activity was probably similar to that of the canonical surfactants. Cattle saliva is available in large amounts easily and cheaply, and it can be used without further purification. Thus, cattle saliva could be a promising additive for efficient saccharification of cellulose on an industrial scale. PMID:26402242

SEGURIDAD DEL PARACETAMOL EN CUBA. 2003 - 2008

Directory of Open Access Journals (Sweden)

Ashley Chao Cardeso

2010-01-01

Full Text Available n observational, descriptive and retrospective study was realized to characterize the behavior of the adverse reactions related to paracetamol, including in the data base of the National Coordinating Unit of Pharmacovigilance, in the period included from January of the 2003 to December of the 2008.Once identified the main's adverse reactions associated to the use of paracetamol and organs' systems more affected it was determined his distribution by sex and groups of ages. In addition, severity and causality were classified accordantly to the avoidable reactions and their causes.Of the 612 notified reactions, the cutaneous eruptions were those of greater quantity (52.2%, corresponding this result with the system of organs more affected, then it was the skin (54.4%. Feminine sex and the group of age between the 16 and 39 years, presented/displayed the majors percents of undesirable effects, with 62.9% and 30.2%, respectively. The behavior, as far as severity and causality, was not different from what it was reported in other studies because the slight reactions predominated (56.7% and probable (80.2%. As far as the avoidable, the 69.1% of the reactions were catalogued like no avoidable, in as much, the errors in the indication of paracetamol constituted the main evitable cause.

The role of saliva in the process of oxidative stress – review of literature

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Anna Krysińska

2016-12-01

Full Text Available Background: Saliva constitutes a first line of defence against free radical-mediated oxidative stress, since the process of mastication and digestion promotes lipid peroxidation. During gingival inflammation, gingival crevicular fluid flow increases the change of saliva composition with products from the inflammatory response, modulating oxidative damages in the oral cavity. Authors review the current literature concerning the reactive oxygen species, oxidants, pro-oxidants and antioxidants in saliva, and methods for assessing the antioxidant capacity of saliva. Comparison of salivary antioxidant status in male and female subjects reveales a significant gender-related difference in saliva composition. The current data demonstrate a significant enhancement of the salivary antioxidant system in juvenile idiopathic arthritis patients. Also patients with chronic renal failure, diabetes and on hemodialysis show increase oxidative stress burden in both serum and saliva. The finding of reduced oral peroxidase levels in smoking subjects may represent a contributory mechanism for initiation and progression of cigarette smoke-related oral diseases such as oral cancer. The results of recent studies indicate that the total antioxidant capacity of saliva decreased in children with HIV infection. Conclusion: Whole saliva may contain simply measured indicators of oxidative processes. This may provide a tool for the development and monitoring of new treatment strategies. A non-invasive determination of the salivary concentrations of antioxidants such as superoxide dismutase (SOD and uric acid (UR allows the evaluation of the defensive capacity of the oral mucosa. Still, there is a need for standardization of methods for saliva sampling and testing protocol.

Photocatalytic degradation of paracetamol: intermediates and total reaction mechanism.

Science.gov (United States)

Moctezuma, Edgar; Leyva, Elisa; Aguilar, Claudia A; Luna, Raúl A; Montalvo, Carlos

2012-12-01

The advanced oxidation of paracetamol (PAM) promoted by TiO(2)/UV system in aqueous medium was investigated. Monitoring this reaction by HPLC and TOC, it was demonstrated that while oxidation of paracetamol is quite efficient under these conditions, its mineralization is not complete. HPLC indicated the formation of hydroquinone, benzoquinone, p-aminophenol and p-nitrophenol in the reaction mixtures. Further evidence of p-nitrophenol formation was obtained following the reaction by UV-vis spectroscopy. Continuous monitoring by IR spectroscopy demonstrated the breaking of the aromatic amide present in PAM and subsequent formation of several aromatic intermediate compounds such as p-aminophenol and p-nitrophenol. These aromatic compounds were eventually converted into trans-unsaturated carboxylic acids. Based on these experimental results, an alternative deacylation mechanism for the photocatalytic oxidation of paracetamol is proposed. Our studies also demonstrated IR spectroscopy to be a useful technique to investigate oxidative mechanisms of pharmaceutical compounds. Copyright © 2012 Elsevier B.V. All rights reserved.

Short- to medium-term effects of consumption of quebracho tannins on saliva production and composition in sheep and goats.

Science.gov (United States)

Salem, A Z M; López, S; Ranilla, M J; González, J S

2013-03-01

Eight Merino sheep (49.4 ± 4.23 kg BW) and 8 Alpine goats (53.2 ± 2.51 kg BW) were used to study the effect of ingestion of quebracho tannins on salivation. Four sheep and 4 goats were individually fed a daily allotment of 20 g DM of alfalfa hay/kg BW (Control). Another 4 sheep and 4 goats were also given 20 g DM of alfalfa hay/kg BW supplemented with 50 g of quebracho/kg DM (Tannin) for a period of 64 d. The saliva secretion from the left parotid gland was collected by insertion of a polyvinyl chloride catheter into the parotid duct and the amount of parotid saliva produced recorded over three 48-h periods on d 1 and 2 (P1), d 31 and 32 (P2), and d 61 and 62 (P3) after the tannin feeding was initiated. The total amount of saliva produced was estimated from rumen water kinetics determined on d 4, d 34, and d 64 of the experiment. Experimental design was completely randomized, with repeated measures on each experimental unit, performing separate analysis for sheep and goats. Parotid saliva production was not affected by the sampling period in either animal species receiving the Control diet. Corresponding values for sheep were 2.04, 2.12, and 2.27 L/d (P = 0.89) and for goats 1.65, 1.79, and 1.86 L/d (P = 0.95). Sheep fed the Tannin diet produced 55, 73, and 107% of the amount of saliva recorded in sheep fed the Control diet on P1, P2, or P3, respectively. Corresponding values in goats were 88, 130, and 134% on P1, P2, or P3, respectively. Estimated total saliva production was not affected (P = 0.50 for sheep and P = 0.97 for goats) by the ingestion of quebracho. There was no difference (P > 0.10) in osmotic pressure, P, Mg, Ca, urea, and protein concentrations in parotid saliva. There were, however, differences in Na and K concentrations in response to the ingestion of quebracho tannins, with Na concentrations increasing (P = 0.05) and K concentrations decreasing (P = 0.04) in sheep saliva and pH increasing (P = 0.05) in goat saliva. In conclusion, the inclusion

Comparative effect of paracetamol, NSAIDs or their combination in postoperative pain management: a qualitative review

DEFF Research Database (Denmark)

Hyllested, M; Jones, S; Pedersen, J L

2002-01-01

BACKGROUND: Quantitative reviews of postoperative pain management have demonstrated that the number of patients needed to treat for one patient to achieve at least 50% pain relief (NNT) is 2.7 for ibuprofen (400 mg) and 4.6 for paracetamol (1000 mg), both compared with placebo. However, direct...... comparisons between paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs) have not been extensively reviewed. The aims of this review are (i) to compare the analgesic and adverse effects of paracetamol with those of other NSAIDs in postoperative pain, (ii) to compare the effects of combined...... paracetamol and NSAID with those of either drug alone, and (iii) to discuss whether the adverse effects of NSAIDs in short-term use are justified by their analgesic effects, compared with paracetamol. METHODS: Medline (1966 to January 2001) and the Cochrane Library (January 2001) were used to perform...

Intoxicación suicida por paracetamol Suicidal poisoning with paracetamol

OpenAIRE

J. Blanco Pampín; N. Morte Tamayo

2002-01-01

La intoxicación por paracetamol es un hecho verdaderamente infrecuente, debido sobre todo al elevado rango terapéutico que posee. Los efectos letales de su ingestión a menudo son el resultado de las complicaciones que originan, aunque por efecto directo del fármaco (intoxicación aguda) se producen tanto en suicidios como a causa de sobredosis en búsqueda de analgesia (intoxicación medicamentosa accidental). El presente artículo expone el caso de una mujer joven con antecedentes psiquiátricos,...

The use of paracetamol (acetaminophen) among a community sample of people with chronic non-cancer pain prescribed opioids.

Science.gov (United States)

Hoban, B; Larance, B; Gisev, N; Nielsen, S; Cohen, M; Bruno, R; Shand, F; Lintzeris, N; Hall, W; Farrell, M; Degenhardt, L

2015-11-01

The regular use of simple analgesics in addition to opioids such as paracetamol (or acetaminophen) is recommended for persistent pain to enhance analgesia. Few studies have examined the frequency and doses of paracetamol among people with chronic non-cancer pain including use above the recommended maximum daily dose. To assess (i) the prevalence of paracetamol use among people with chronic non-cancer pain prescribed opioids, (ii) assess the prevalence of paracetamol use above the recommended maximum daily dose and (iii) assess correlates of people who used paracetamol above the recommended maximum daily dose including: age, gender, income, education, pain severity and interference, use of paracetamol/opioid combination analgesics, total opioid dose, depression, anxiety, pain self-efficacy or comorbid substance use, among people prescribed opioids for chronic non-cancer pain. This study draws on baseline data collected for the Pain and Opioids IN Treatment (POINT) study and utilises data from 962 interviews and medication diaries. The POINT study is national prospective cohort of people with chronic non-cancer pain prescribed opioids. Participants were recruited from randomly selected pharmacies across Australia. Sixty-three per cent of the participants had used paracetamol in the past week (95% CI = 59.7-65.8). Among the paracetamol users 22% (95% CI = 19.3-24.6) had used paracetamol/opioid combination analgesics and 4.8% (95% CI = 3.6-6.3) had used paracetamol above the recommended maximum daily dose (i.e. > 4000 mg/day). Following binomial logistic regression (χ(2) = 25.98, df = 10, p = 0.004), people who had taken above the recommended maximum daily dose were less likely to have low income (AOR = 0.52, 95% CI = 0.27-0.99), more likely to use paracetamol/opioid combination analgesics (AOR = 2.01, 95% CI = 1.02-3.98) and more likely to take a higher opioid dose (AOR = 1.00, 95% CI = 1.00-1.01). The majority of people with chronic non-cancer pain prescribed

Radioimmunological analysis of circadian rhythms of cortisol and melatonin in saliva

International Nuclear Information System (INIS)

Demel, A.W.

1990-12-01

Since blood cortisol (F) and melatonin (MLT) display a circadian secretion pattern and since the saliva concentration of this hormones is an excellent indicator of its blood levels the measurement of salivary F and MLT may be used for examining circadian rhythmicity. In this study the relationship between salivary F and MLT was explored. For this purpose it was necessary first to establish and validate a radioimmunoassay for F in saliva: salivary F was determined by a direct radioimmunoassay using cortisol-3-(O-carboxymethyl) oximino-(2-( 125 I)iodohistamin) as tracer and cortisol-3-CMO-BSA antiserum. The parallel measurement of F levels in saliva and serum of adults gave an excellent correlation (r=0.87, p 0.00956x ). Serum F was assayed on the Abott TDX-System using a radioimmunofluorescence method. Secondly, using this assay the circadian saliva F pattern was determined as well as the pattern of salivary MLT in 9 young, healthy volunteers. For saliva MLT estimations a previously published method was applied (Schulz et al 1990). Using a computerized program (RHYTHM) written by Eve v. Cauter (1979), the hormone data of each individuum were examined for circadian rhythmicity and its acrophase (time of occurrence of the maximum of a sinusoid fitted to the data). The F acrophase occurred between 7:00 and 12:00 h (mean: 3:33 h, SD: 104.4 min). The easy stress-free non invasive nature of saliva collection makes saliva to one of the most accessible body fluids and of high value in studying the circadian system in healthy humans as well as in infants, children, pregnant women and anaemic patients. Measurements of salivary F and MLT may help to elucidate not only the circadian rhythms of these hormones under normal and pathological conditions but it may also provide insight in physiology and pathology of the circadian system in general. (author)

Effect of acetylcysteine on prothrombin index in paracetamol poisoning without hepatocellular injury

DEFF Research Database (Denmark)

Schmidt, Lars E; Knudsen, Tore Tveit; Dalhoff, Kim

2002-01-01

Acetylcysteine treatment reduces liver damage after paracetamol overdose, but can affect the prothrombin index, which is used to assess the progress of overdose patients. We aimed to assess retrospectively the effect of intravenous acetylcysteine on the prothrombin index in patients with paraceta......Acetylcysteine treatment reduces liver damage after paracetamol overdose, but can affect the prothrombin index, which is used to assess the progress of overdose patients. We aimed to assess retrospectively the effect of intravenous acetylcysteine on the prothrombin index in patients...... with paracetamol poisoning without signs of hepatocellular injury. Prothrombin index had been recorded before, and serially during, acetylcysteine treatment in 87 patients. After initiation of treatment, prothrombin index decreased (mean 0.33, 95% CI 0.29-0.38) in all patients, and was strongly associated...... with the start of acetylcysteine infusion. In patients with uncomplicated paracetamol poisoning, a fall in this index might be misinterpreted as a sign of liver failure, leading to prolonged treatment time....

Determinação de paracetamol em produtos farmacêuticos usando um biossensor de pasta de carbono modificado com extrato bruto de abobrinha (Cucurbita pepo

Directory of Open Access Journals (Sweden)

Vieira Iolanda Cruz

2003-01-01

Full Text Available Crude extracts of several vegetables such as peach (Prunus persica, yam (Alocasia macrorhiza, manioc (Manihot utilissima, artichoke (Cynara scolymus L, sweet potato (Ipomoea batatas (L. Lam., turnip (Brassica campestre ssp. rapifera, horseradish (Armoracia rusticana and zucchini (Cucurbita pepo were investigated as the source of peroxidase (POD: EC 1.11.1.7. Among those, zucchini (Cucurbita pepo crude extract was found to be the best one. This enzyme in the presence of hydrogen peroxide catalyses the oxidation of paracetamol to N-acetyl-p-benzoquinoneimine which the electrochemical reduction back to paracetamol was obtained at a peak potential of fraction three-quarters0.10V. A cyclic voltammetric study was performed by scanning the potential from + 0.5 to fraction three-quarters 0.5 V. The recovery of paracetamol from two samples ranged from 97.3 to 106% and a rectilinear calibration curve for paracetamol concentration from 1.2x10-4 to 2.5x10-3 mol L-1 (r=0.9965 were obtained. The detection limit was 6.9x10-5 mol L-1 and the relative standard deviation was less than 1.1% for a solution containing 2.5x10-3 mol L-1 paracetamol and 2.0x10-3 mol L-1 hydrogen peroxide (n=12. The results obtained for paracetamol in pharmaceutical products using the proposed biosensor and Pharmacopoeial procedures are in agreement at the 95% confidence level.

Prenatal paracetamol exposure is associated with shorter anogenital distance in male infants

Science.gov (United States)

Fisher, B.G.; Thankamony, A.; Hughes, I.A.; Ong, K.K.; Dunger, D.B.; Acerini, C.L.

2016-01-01

STUDY QUESTION What is the relationship between maternal paracetamol intake during the masculinisation programming window (MPW, 8–14 weeks of gestation) and male infant anogenital distance (AGD), a biomarker for androgen action during the MPW? SUMMARY ANSWER Intrauterine paracetamol exposure during 8–14 weeks of gestation is associated with shorter AGD from birth to 24 months of age. WHAT IS ALREADY KNOWN The increasing prevalence of male reproductive disorders may reflect environmental influences on foetal testicular development during the MPW. Animal and human xenograft studies have demonstrated that paracetamol reduces foetal testicular testosterone production, consistent with reported epidemiological associations between prenatal paracetamol exposure and cryptorchidism. STUDY DESIGN, SIZE, DURATION Prospective cohort study (Cambridge Baby Growth Study), with recruitment of pregnant women at ~12 post-menstrual weeks of gestation from a single UK maternity unit between 2001 and 2009, and 24 months of infant follow-up. Of 2229 recruited women, 1640 continued with the infancy study after delivery, of whom 676 delivered male infants and completed a medicine consumption questionnaire. PARTICIPANTS/MATERIALS, SETTING, METHOD Mothers self-reported medicine consumption during pregnancy by a questionnaire administered during the perinatal period. Infant AGD (measured from 2006 onwards), penile length and testicular descent were assessed at 0, 3, 12, 18 and 24 months of age, and age-specific Z scores were calculated. Associations between paracetamol intake during three gestational periods (14 weeks) and these outcomes were tested by linear mixed models. Two hundred and twenty-five (33%) of six hundred and eighty-one male infants were exposed to paracetamol during pregnancy, of whom sixty-eight were reported to be exposed during 8–14 weeks. AGD measurements were available for 434 male infants. MAIN RESULTS AND THE ROLE OF CHANCE Paracetamol exposure during 8–14

Prenatal and infant paracetamol exposure and development of asthma: the Norwegian Mother and Child Cohort Study.

Science.gov (United States)

Magnus, Maria C; Karlstad, Øystein; Håberg, Siri E; Nafstad, Per; Davey Smith, George; Nystad, Wenche

2016-04-01

Paracetamol exposure has been positively associated with asthma development. The relative importance of prenatal vs infant exposure and confounding by indication remains elusive. We examined the association of prenatal and infant (first 6 months) paracetamol exposure with asthma development while addressing confounding by indication. We used information from the Norwegian Mother and Child Cohort Study, including 53169 children for evaluation of current asthma at 3 years, 25394 for current asthma at 7 years and 45607 for dispensed asthma medications at 7 years in the Norwegian Prescription Database. We calculated adjusted relative risks (adj. RR) and 95% confidence intervals (CI) using log-binomial regression. There were independent modest associations between asthma at 3 years with prenatal paracetamol exposure (adj. RR 1.13; 95% CI: 1.02-1.25) and use of paracetamol during infancy (adj. RR 1.29; 95% CI: 1.16-1.45). The results were consistent for asthma at 7 years. The associations with prenatal paracetamol exposure were seen for different indications (pain, respiratory tract infections/influenza and fever). Maternal pain during pregnancy was the only indication that showed an association both with and without paracetamol use. Maternal paracetamol use outside pregnancy and paternal paracetamol use were not associated with asthma development. In a secondary analysis, prenatal ibuprofen exposure was positively associated with asthma at 3 years but not asthma at 7 years. This study provides evidence that prenatal and infant paracetamol exposure have independent associations with asthma development. Our findings suggest that the associations could not be fully explained by confounding by indication. © The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

Concomitant overdosing of other drugs in patients with paracetamol poisoning

DEFF Research Database (Denmark)

Schmidt, Lars E; Dalhoff, Kim

2002-01-01

of the paracetamol intoxication. METHODS: Six hundred and seventy-one consecutive patients admitted with paracetamol poisoning were studied and concomitant drug intake was recorded. The relative risk of hepatic encephalopathy, death or liver transplantation, hepatic dysfunction, liver cell damage, and renal...... was a protective factor in the development of hepatic encephalopathy (OR 0.26; CI 0.07, 0.96). Concomitant acetylsalicylic acid overdose was a risk factor in the development of hepatic encephalopathy (OR 4.87; CI 1.52, 15.7) and death or liver transplantation (OR 6.04; CI 1.69, 21.6). A tendency towards a more...... favourable outcome was observed in patients with concomitant NSAID overdose. CONCLUSIONS: Concomitant overdosing of benzodiazepines or analgesics is frequent in patients admitted with paracetamol poisoning. Concomitant benzodiazepine or acetylsalicylic acid overdose was associated with more severe toxicity...

Scalp hair and saliva as biomarkers in determination of mercury levels in Iranian women: Amalgam as a determinant of exposure

International Nuclear Information System (INIS)

Fakour, H.; Esmaili-Sari, A.; Zayeri, F.

2010-01-01

The aim of this study was to determine the relationship between mercury concentrations in saliva and hair in women with amalgam fillings and its relation with age and number of amalgam fillings. Eighty-two hair and saliva samples were collected randomly from Iranian women who have the same fish consumption pattern and free from occupational exposures. The mean ± SD age of these women was 29.37 ± 8.12 (ranged from 20 to 56). The determination of Hg level in hair samples was carried out by the LECO, AMA 254, Advanced Mercury Analyzer according to ASTM, standard No. D-6722. Mercury concentration in saliva samples was analyzed by PERKIN-ELMER 3030 Cold Vapor Atomic Absorption Spectrophotometer. The mean ± SD mercury level in the women was 1.28 ± 1.38 μg/g in hair and 4.14 ± 4.08 μg/l in saliva; and there were positive correlation among them. A significant correlation was also observed between Hg level of saliva (Spearman's ρ = 0.93, P < 0.001) and hair (Spearman's ρ = 0.92, P < 0.001) with number of amalgam fillings. According to the results, we can conclude that amalgam fillings may be an effective source for high Hg concentration in hair and releasing the mercury to the saliva samples.

Pregabalin and dexamethasone in combination with paracetamol for postoperative pain control after abdominal hysterectomy. A randomized clinical trial

DEFF Research Database (Denmark)

Rasmussen, M L; Dierking, G; Lech, K

2008-01-01

BACKGROUND: Multimodal analgesia may be important for optimal postoperative pain treatment and facilitation of early mobilization and recovery. We investigated the analgesic effect of pregabalin and dexamethasone in combination with paracetamol after abdominal hysterectomy. METHODS: One hundred...... and sixteen patients were randomly assigned to either group A (paracetamol+placebo x 2), group B (paracetamol+pregabalin+placebo) or group C (paracetamol+pregabalin+dexamethasone). According to randomization and preoperatively, patients received paracetamol 1000 mg, pregabalin 300 mg, dexamethasone 8 mg...... or placebo. General anaesthesia was performed. Postoperative pain treatment was paracetamol 1000 mg x 4 and patient-controlled intravenous morphine, 2.5 mg bolus. Nausea was treated with ondansetron. Morphine consumption, pain score (visual analogue scale) at rest and during mobilization, nausea, sedation...

Quantification of piroxicam and 5'-hydroxypiroxicam in human plasma and saliva using liquid chromatography-tandem mass spectrometry following oral administration.

Science.gov (United States)

Calvo, Adriana Maria; Santos, Gabriel Mulinari; Dionísio, Thiago José; Marques, Maria Paula; Brozoski, Daniel Thomas; Lanchote, Vera Lúcia; Fernandes, Maria Helena Raposo; Faria, Flávio Augusto Cardoso; Santos, Carlos Ferreira

2016-02-20

Saliva sampling used to quantify piroxicam and 5'-hydroxypiroxicam is a noninvasive and painless method when compared to sequential blood sampling. For that, a rapid, selective and sensitive liquid chromatography-tandem mass spectrometric method for simultaneous determination of piroxicam and 5'-hydroxypiroxicam in saliva and human plasma was developed and validated. Piroxicam and its major metabolite were separated using a LiChroCART 125-4 RP Select-B Sorbent C18 column using a mixture of methanol and 2% phosphoric acid (pH 2.7) (70:30, v/v) for the mobile phase with a flow injection of 1mL/min. The run time was 4min. Volunteers had saliva and blood sampled before, 1, 2, 3, 4, 5, 6, 8, 11, 24, 48 and 72h after taking a 20mg oral dose of piroxicam. The pharmacokinetic parameters of piroxicam in plasma samples were as follows: AUC0-72 (64819hng/mL), predicted clearance (0.2L/h), distribution volume (14.8L), elimination half-life (50.7h) and saliva/plasma concentration ratio (0.003). The estimation of all pharmacokinetic parameters for 5'-hydroxypiroxicam would require collections beyond 72h; however, it was possible to quantify the mean maximum concentration (133ng/mL), time to peak concentration (53.6h), mean AUC0-72 (6213hng/mL), predicted clearance (110.3L/h) and saliva/plasma concentration ratio (0.04). The developed methods proved effective and sensitive for determining the lower quantification limit of piroxicam in plasma (6.1ng/mL) and saliva (0.15ng/mL) and of 5'-hydroxypiroxicam in plasma (1.2ng/mL) and saliva (0.15ng/mL). Copyright © 2015 Elsevier B.V. All rights reserved.

Spinal cholinergic involvement after treatment with aspirin and paracetamol in rats

DEFF Research Database (Denmark)

Abelson, Klas S P; Kommalage, Mahinda; Höglund, A Urban

2004-01-01

Aspirin and paracetamol have been shown to suppress non-inflammatory pain conditions like thermal, visceral and mechanical pain in mice and rats. The non-inflammatory antinociception appears to be mediated by central receptor mechanisms, such as the cholinergic system. In this study, we tested...... the hypothesis that the non-inflammatory antinociception of aspirin and paracetamol could be mediated by an increase of intraspinal acetylcholine release. Microdialysis probes were placed intraspinally in anesthetized rats for acetylcholine sampling. Subcutaneously administered aspirin 100 and 300 mg....../kg increased, while paracetamol 300 mg/kg decreased intraspinal acetylcholine release. Intraspinal drug administration did not affect acetylcholine release. Our results suggest that an increased intraspinal acetylcholine release could be involved in part of the non-inflammatory pain suppression by aspirin...

Radiolytic degradation of paracetamol in dilute aqueous solution

Energy Technology Data Exchange (ETDEWEB)

Szabo, L [Hungarian Academy of Sciences, Budapest (Hungary). Inst. of Isotopes; Budapest University of Technology and Economics, Budapest (Hungary); Toth, T [Budapest University of Technology and Economics, Budapest (Hungary); Homlok, R; Takacs, E; Wojnarovits, L [Hungarian Academy of Sciences, Budapest (Hungary). Inst. of Isotopes

2011-07-01

Complete text of publication follows. Paracetamol or with name acetaminophen is widely used as analgesic and antipyretic drug. Due to its heavy use it is regularly detected in the surface waters. The degradation of the compound formerly was studied in several advanced oxidation processes (UV/H{sub 2}O{sub 2}, UV/TiO{sub 2}, electrochemical oxidation, ozonation). Here we report on the radiolytic degradation. In the experimental work we combined a wide variety of techniques. For the investigation of the intermediates pulse radiolysis, for end-product experiments (decolouration, mineralization) gamma irradiation were used together with UV-Vis spectroscopy, HPLC separation (with diode array and MS-MS detection), chemical oxygen demand, total organic carbon content and toxicity measurements. {sup {center_dot}O}H radicals are the main oxidative species during irradiation. They add to the aromatic ring producing hydroxycyclohexadienyl type radicals. These radicals either transform to hydroxy-paracetamol stable products in several reaction steps, or after water elimination transform to semi-iminoquinone radical. The reaction of hydroxycyclohexadienyl radicals with O{sub 2} yields peroxi radicals. The latter radicals may eliminate HO{sub 2}{sup {center_dot}} or undergo ring opening and transformation, first to different carboxylic acids, and finally (mineralization) to CO{sub 2}, H{sub 2}O and NH{sub 3} or NO{sub 2}. Paracetamol has a relatively low toxicity. In 10{sup -3} mol dm{sup -3} DCF solution after irradiation some products (e.g. hydroquinone, acetamide) are more toxic than paracetamol. By increasing the dose the toxicity suddenly decreases. It seems that the toxic products are highly sensitive to irradiation treatment.

Chemometrics resolution and quantification power evaluation: Application on pharmaceutical quaternary mixture of Paracetamol, Guaifenesin, Phenylephrine and p-aminophenol

Science.gov (United States)

Yehia, Ali M.; Mohamed, Heba M.

2016-01-01

Three advanced chemmometric-assisted spectrophotometric methods namely; Concentration Residuals Augmented Classical Least Squares (CRACLS), Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS) and Principal Component Analysis-Artificial Neural Networks (PCA-ANN) were developed, validated and benchmarked to PLS calibration; to resolve the severely overlapped spectra and simultaneously determine; Paracetamol (PAR), Guaifenesin (GUA) and Phenylephrine (PHE) in their ternary mixture and in presence of p-aminophenol (AP) the main degradation product and synthesis impurity of Paracetamol. The analytical performance of the proposed methods was described by percentage recoveries, root mean square error of calibration and standard error of prediction. The four multivariate calibration methods could be directly used without any preliminary separation step and successfully applied for pharmaceutical formulation analysis, showing no excipients' interference.

Developmental changes rather than repeated administration drive paracetamol glucuronidation in neonates and infants

NARCIS (Netherlands)

E.H.J. Krekels (Elke); S. Van Ham (Saskia); K.M. Allegaert (Karel); J.N. de Hoon; D. Tibboel (Dick); M. Danhof (Meindert); C.A.J. Knibbe (Catherijne)

2015-01-01

textabstractPurpose: Based on recovered metabolite ratios in urine, it has been concluded that paracetamol glucuronidation may be up-regulated upon multiple dosing. This study investigates paracetamol clearance in neonates and infants after single and multiple dosing using a population modelling

Fluoride Increase in Saliva and Dental Biofilm due to a Meal Prepared with Fluoridated Water or Salt: A Crossover Clinical Study.

Science.gov (United States)

Lima, Carolina V; Tenuta, Livia M A; Cury, Jaime A

2018-06-07

Knowledge about fluoride delivery to oral fluids from foods cooked with fluoridated water and salt is scarce, and no study has evaluated fluoride concentrations in saliva or biofilm during meal consumption. In this randomized double-blind crossover study, 12 volunteers ingested meals (rice, beans, meat, and legumes) prepared with nonfluoridated water and salt (control group), fluoridated water (0.70 mg F/L; water group), and fluoridated salt (183.7 mg F/kg; salt group). Whole saliva was collected before meal ingestion, during mastication, and up to 2 h after meal ingestion. Dental biofilm was collected before and immediately after meal ingestion. Fluoride concentrations in saliva and dental biofilm were determined by an ion-specific electrode. The mean (±standard deviation; n = 4) fluoride concentrations in meals prepared for the control, water, and salt groups were 0.039 ± 0.01, 0.43 ± 0.04, and 1.71 ± 0.32 μg F/g, respectively. The three groups had significantly different fluoride concentrations in saliva collected during mastication (p water > control). The fluoride concentration in saliva returned to baseline 30 min after meal ingestion in the water group but remained high for up to 2 h in the salt group (p = 0.002). The fluoride concentration in biofilm fluid differed only between the salt and control groups (p = 0.008). The mastication of foods cooked with fluoridated water and salt increases fluoride concentrations in oral fluids and may contribute to the local effect of these community-based fluoride interventions on caries control. © 2018 S. Karger AG, Basel.

Intrauterine Exposure to Paracetamol and Aniline Impairs Female Reproductive Development by Reducing Follicle Reserves and Fertility

DEFF Research Database (Denmark)

Holm, Jacob Bak; Mazaud-Guittot, Severine; Danneskiold-Samsøe, Niels Banhos

2016-01-01

in shortening of the anogenital distance in adult offspring, suggesting that fetal hormone signaling had been disturbed. Female offspring of paracetamol-exposed mothers had ovaries with diminished follicle reserve and reduced fertility. Fetal gonads of exposed animals had also reduced gonocyte numbers......, suggesting that the reduced follicle count in adults could be due to early disruption of germ cell development. However, ex vivo cultures of ovaries from 12.5 days post coitum fetuses showed no decrease in proliferation or expression following exposure to paracetamol. This suggests that the effect...... of paracetamol occurs prior to this developmental stage. Accordingly, using embryonic stem cells as a proxy for primordial germ cells we show that paracetamol is an inhibitor of cellular proliferation, but without cytotoxic effects. Collectively, our data show that intrauterine exposure to paracetamol at levels...

PAIS 2 (Paracetamol [Acetaminophen] in Stroke 2): Results of a Randomized, Double-Blind Placebo-Controlled Clinical Trial.

Science.gov (United States)

de Ridder, Inger R; den Hertog, Heleen M; van Gemert, H Maarten A; Schreuder, A H C M L Tobien; Ruitenberg, Annemieke; Maasland, E Lisette; Saxena, Ritu; van Tuijl, Jordie H; Jansen, Ben P W; Van den Berg-Vos, Renske M; Vermeij, Frederique; Koudstaal, Peter J; Kappelle, L Jaap; Algra, Ale; van der Worp, H Bart; Dippel, Diederik W J

2017-04-01

Subfebrile body temperature and fever in the first days after stroke are strongly associated with unfavorable outcome. A subgroup analysis of a previous trial suggested that early treatment with paracetamol may improve functional outcome in patients with acute stroke and a body temperature of ≥36.5°C. In the present trial, we aimed to confirm this finding. PAIS 2 (Paracetamol [Acetaminophen] in Stroke 2) was a multicenter, randomized, double-blind, placebo-controlled clinical trial. We aimed to include 1500 patients with acute ischemic stroke or intracerebral hemorrhage within 12 hours of symptom onset. Patients were treated with paracetamol in a daily dose of 6 g or matching placebo for 3 consecutive days. The primary outcome was functional outcome at 3 months, assessed with the modified Rankin Scale and analyzed with multivariable ordinal logistic regression. Because of slow recruitment and lack of funding, the study was stopped prematurely. Between December 2011 and October 2015, we included 256 patients, of whom 136 (53%) were allocated to paracetamol. In this small sample, paracetamol had no effect on functional outcome (adjusted common odds ratio, 1.15; 95% confidence interval, 0.74-1.79). There was no difference in the number of serious adverse events (paracetamol n=35 [26%] versus placebo n=28 [24%]). Treatment with high-dose paracetamol seemed to be safe. The effect of high-dose paracetamol on functional outcome remains uncertain. Therefore, a large trial of early treatment with high-dose paracetamol is still needed. URL: http://www.trialregister.nl. Unique identifier: NTR2365. © 2017 American Heart Association, Inc.

SALIVA AS A DIAGNOSTIC FLUID

Directory of Open Access Journals (Sweden)

Pezelj-Ribarić Sonja

2015-12-01

Full Text Available Saliva is a readily available oral fluid with many functions, from digestion, maintenance of oral tissues' integrity, to caries prevention. Changes regarding its secretion may be divided into qualitative and quantitative: both of them are a consequence of certain conditions/diseases (e.g. internal factors or nutrients/drugs ingested (e.g. external factors. During the last 15 years, technological advances gave a significant momentum to utilization of saliva as a diagnostic tool. Analysis of saliva, just like the blood analysis, has two main objectives: to identify the subjects suffering from a certain disorder, and to follow the development and progress of therapy. This paper provides an overview of possibilities for the use of saliva for diagnostic purposes and gives specific examples of some clinical investigations, with the final aim to stimulate the use of this noninvasive means for the health care promotion.

Protective Role of Carnitine against the Harmful Biological Effects of Paracetamol and Radiation Exposure in Male Albino Rats

International Nuclear Information System (INIS)

Abd El Rahman, N.A.

2012-01-01

L-carnitine, a natural component of mammalian tissue, is a necessary factor in the utilization of long-chain fatty acids to produce energy. Furthermore it has been shown to protect cells from per oxidative stress. The objective of the present study was to evaluate the efficacy of L-carnitine on hepatotoxicity and nephrotoxicity induced by paracetamol, γ-radiation, and paracetamol + γ-radiation. Male albino rats were divided into 8 groups. 1-Control group: rats not subject to any treatment, 2-Carnitine group: rats received L-carnitine (0.5 ml/Kg body weight) via intraperitoneal injection during 21 days, 3-Paracetamol group: rats received paracetamol (50 mg/kg body) via intraperi-toneal injection during 21 days, 4- Carnitine + Paracetamol group: rats received L-carnitine in parallel to paracetamol treatment, 5- Radiation groups: rats were whole body gamma irradiated with 7 Gy, 6- Carnitine + Radiation group: rats received L-carnitine for 21 days before whole body gamma irradiation with 7Gy, 7- Paracetamol + Radiation group: rats received paracetamol during 21 days before whole body gamma irradiation, 8- Carnitine + Paracetamol + Radiation group: rats received L-carnitine parallel to paracetamol during 21 days before whole body gamma irradiation.The results demonstrated that rats receiving paracetamol, as well as whole body gamma irradiated rats and rats receiving paracetamol and irradiated showed a significant increase of alanine amino transferase (ALT), aspartate amino transferase (AST), and alkaline phosphatase (ALP) activities, and a significant decrease of gamma-glutamyl transpeptidase (GGT) activity indicating liver injury. A significant increase of urea, creatinine and uric acid levels was recorded also indicating kidney damage. Alteration in liver and kidney functions was accompanied by a significant increase in the content of thiobarbituric acid reactive substances (TBARS) associated with a significant decrease in glutathione (GSH) content and superoxide

Paracetamol as a prophylactic analgesic for hysterosalpingography: A double blind randomized controlled trial

International Nuclear Information System (INIS)

Elson, E.M.; Ridley, N.T.F.

2000-01-01

AIM: To evaluate the effectiveness of paracetamol as a prophylactic analgesic for hysterosalpingography (HSG). DESIGN: A prospective double blind randomized controlled trial comparing one 1 g of paracetamol (SmithKline Beecham, Brentford, U.K.) to placebo taken 30 min before HSG. One hundred consecutive out-patients were studied prospectively. The analgesic effectiveness during the procedure and at 24 h and 1 week post procedure was analysed by a postal pain score questionnaire. Additional data on the ethnicity of the patient, sex and level of experience of the radiologist performing the hysterosalpingogram, the parity of the patient, the ease of the procedure, and whether pathology was identified were also recorded. RESULTS: Eighty-eight patients (88%) replied, 39 (44%) received paracetamol and 49 placebo (56%). During the procedure 3/39 (7%) of women in the paracetamol group were pain-free compared to 9/49 (18%) in the placebo group, which was not significant (P = 0.11). At 24 h, 15/39 (38%) of women in the paracetamol group were pain-free compared to 20/49 (41%) in the placebo group, which was not significant (P = 0.82). At 1 week, 27/39 (69%) of women in the paracetamol group were pain-free compared to 29/49 (59%) in the placebo group, which was not significant (P = 0.33). No significant difference in mean pain scores was determined during the procedure (P 0.91), or at 24 h post procedure (P = 0.94). Similarly, no difference in mean pain scores was identified with regard to the ethnicity of the patient, the sex of the radiologist performing the procedure, the level of experience of the radiologist performing the procedure, or whether pathology was present or not. Difficult cannulations were associated with higher mean pain scores, however, there was no difference in mean pain scores between the paracetamol or placebo groups for both easy and difficult cannulations. CONCLUSION: Paracetamol is not effective as a prophylactic analgesic for HSG. If a prophylactic

Paracetamol as a prophylactic analgesic for hysterosalpingography: A double blind randomized controlled trial

Energy Technology Data Exchange (ETDEWEB)

Elson, E.M.; Ridley, N.T.F

2000-09-01

AIM: To evaluate the effectiveness of paracetamol as a prophylactic analgesic for hysterosalpingography (HSG). DESIGN: A prospective double blind randomized controlled trial comparing one 1 g of paracetamol (SmithKline Beecham, Brentford, U.K.) to placebo taken 30 min before HSG. One hundred consecutive out-patients were studied prospectively. The analgesic effectiveness during the procedure and at 24 h and 1 week post procedure was analysed by a postal pain score questionnaire. Additional data on the ethnicity of the patient, sex and level of experience of the radiologist performing the hysterosalpingogram, the parity of the patient, the ease of the procedure, and whether pathology was identified were also recorded. RESULTS: Eighty-eight patients (88%) replied, 39 (44%) received paracetamol and 49 placebo (56%). During the procedure 3/39 (7%) of women in the paracetamol group were pain-free compared to 9/49 (18%) in the placebo group, which was not significant (P = 0.11). At 24 h, 15/39 (38%) of women in the paracetamol group were pain-free compared to 20/49 (41%) in the placebo group, which was not significant (P = 0.82). At 1 week, 27/39 (69%) of women in the paracetamol group were pain-free compared to 29/49 (59%) in the placebo group, which was not significant (P = 0.33). No significant difference in mean pain scores was determined during the procedure (P 0.91), or at 24 h post procedure (P = 0.94). Similarly, no difference in mean pain scores was identified with regard to the ethnicity of the patient, the sex of the radiologist performing the procedure, the level of experience of the radiologist performing the procedure, or whether pathology was present or not. Difficult cannulations were associated with higher mean pain scores, however, there was no difference in mean pain scores between the paracetamol or placebo groups for both easy and difficult cannulations. CONCLUSION: Paracetamol is not effective as a prophylactic analgesic for HSG. If a prophylactic

Paracetamol (acetaminophen) for acute treatment of episodic tension-type headache in adults.

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Stephens, Guy; Derry, Sheena; Moore, R Andrew

2016-06-16

Tension-type headache (TTH) affects about 1 person in 5 worldwide. It is divided into infrequent episodic TTH (fewer than one headache per month), frequent episodic TTH (two to 14 headaches per month), and chronic TTH (15 headache days a month or more). Paracetamol (acetaminophen) is one of a number of analgesics suggested for acute treatment of headaches in frequent episodic TTH. To assess the efficacy and safety of paracetamol for the acute treatment of frequent episodic TTH in adults. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (CRSO), MEDLINE, EMBASE, and the Oxford Pain Relief Database to October 2015, and also reference lists of relevant published studies and reviews. We sought unpublished studies by asking personal contacts and searching online clinical trial registers and manufacturers' websites. We included randomised, double-blind, placebo-controlled studies (parallel-group or cross-over) using oral paracetamol for symptomatic relief of an acute episode of TTH. Studies had to be prospective, with participants aged 18 years or over, and include at least 10 participants per treatment arm. Two review authors independently assessed studies for inclusion and extracted data. We used the numbers of participants achieving each outcome to calculate the risk ratio (RR) and number needed to treat for one additional beneficial outcome (NNT) or one additional harmful outcome (NNH) for oral paracetamol compared to placebo or an active intervention for a range of outcomes, predominantly those recommended by the International Headache Society (IHS).We assessed the evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation) and created 'Summary of findings' tables. We included 23 studies, all of which enrolled adults with frequent episodic TTH. Twelve studies used the IHS diagnostic criteria or similar, six used the older classification of the Ad Hoc Committee, and five did not describe specific diagnostic criteria

Paracetamol (acetaminophen) for patent ductus arteriosus in preterm or low-birth-weight infants.

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Ohlsson, Arne; Shah, Prakeshkumar S

2015-03-11

In preterm newborns, the ductus arteriosus frequently fails to close and the infants require medical or surgical closure of the patent ductus arteriosus (PDA). A PDA can be treated surgically or medically with one of two prostaglandin inhibitors, indomethacin or ibuprofen. Case reports suggest that paracetamol may be an alternative for the closure of a PDA. Concerns have been raised that in neonatal mice paracetamol may cause adverse effects on the developing brain, and an association between prenatal exposure to paracetamol and later development of autism or autism spectrum disorder has been reported. To determine the efficacy and safety of intravenous or oral paracetamol compared with placebo or no intervention, intravenous indomethacin, intravenous or oral ibuprofen, or with other cyclo-oxygenase inhibitors for closure of a PDA in preterm or low-birth-weight infants. We used the standard search strategy of the Cochrane Neonatal Review Group. This included electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL, Cochrane Library), MEDLINE, EMBASE and CINAHL. We searched abstracts from the meetings of the Pediatric Academic Societies and the Perinatal Society of Australia and New Zealand. We searched clinicaltrials.gov; controlled-trials.com; anzctr.org.au; World Health Organization International Clinical Trials Registry Platform at who.int/ictrp for ongoing trials and the Web of Science for articles quoting identified randomised controlled trials. We searched the first 200 hits on Google Scholar(TM) to identify grey literature. All searches were conducted in December 2013. A repeat search of MEDLINE in August 2014 did not identify any new trials. We identified two randomised controlled trials (RCTs) that compared oral paracetamol to oral ibuprofen for the treatment of an echocardiographically diagnosed PDA in infants born preterm (≤ 34 weeks postmenstrual age (PMA)). We performed data collection and analyses in accordance with the

Estimation of the growth kinetics for the cooling crystallisation of paracetamol and ethanol solutions

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Mitchell, Niall A.; Ó'Ciardhá, Clifford T.; Frawley, Patrick J.

2011-08-01

This work details the estimation of the growth kinetics of paracetamol in ethanol solutions for cooling crystallisation processes, by means of isothermal seeded batch experiments. The growth kinetics of paracetamol crystals were evaluated in isolation, with the growth rate assumed to be size independent. Prior knowledge of the Metastable Zone Width (MSZW) was required, so that supersaturation ratios of 1.7-1.1 could be induced in solution without the occurrence of nucleation. The technique involved the utilisation of two in-situ Process Analytical Techniques (PATs), with a Focused Beam Reflectance Measurement (FBRM ®) utilised to ensure that negligible nucleation occurred and an Attenuated Total Reflectance-Fourier Transform Infrared (ATR-FTIR) probe employed for online monitoring of solute concentration. Initial Particle Size Distributions (PSDs) were used in conjunction with desupersaturation profiles to determine the growth rate as a function of temperature and supersaturation. Furthermore, the effects of seed loading and size on the crystal growth rate were investigated. A numerical model, incorporating the population balance equation and the method of moments, was utilised to describe the crystal growth process. Experimental parameters were compared to the model simulation, with the accuracy of the model validated by means of the final product PSDs and solute concentration.

RP-HPLC-DAD method for the determination of phenylepherine, paracetamol, caffeine and chlorpheniramine in bulk and marketed formulation

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A.P. Dewani

2014-11-01

Full Text Available A simple, specific and accurate isocratic RP-HPLC-DAD method was developed for the simultaneous determination of phenylephrine, paracetamol, caffeine and chlorpheniramine in bulk and tablet dosage form. The four contents are present in variable concentrations and have variable chromatographic behavior making the process of analysis very difficult. For present studies a reversed-phase C-18 column (150 mm × 4.5 mm i.d., particle size 5 μm with mobile phase consisting of acetonitrile, methanol and 10 Mm phosphate buffer 16:22:62 (v/v (pH of buffer 2.5 ± 0.02, adjusted with ortho phosphoric acid was used. The flow rate was 1.0 ml/min and eluents were monitored at 280 nm. The mean retention times of phenylephrine, paracetamol, caffeine and chlorpheniramine were found to be 1.8, 3.1, 5.2 and 10.9 min, respectively. The method was validated in terms of linearity, range, specificity, accuracy, precision and robustness. The proposed method was successfully applied to the estimation of phenylephrine, paracetamol, caffeine and chlorpheniramine in combined tablet dosage form.

Patients' knowledge about paracetamol (acetaminophen): a study in a French hospital emergency department.

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Boudjemai, Y; Mbida, P; Potinet-Pagliaroli, V; Géffard, F; Leboucher, G; Brazier, J-L; Allenet, B; Charpiat, B

2013-07-01

Paracetamol is the most widely used analgesic and antipyretic drug. In France, little is known concerning patients' knowledge and beliefs about paracetamol. To determine how much outpatients attending an emergency department know about paracetamol. A semi-structured questionnaire was applied to patients consulting for non-severe medical or traumatic conditions. Thirty-three (45%) of 73 participating patients knew that paracetamol was the active ingredient of the medication they used to reduce pain and/or fever. Three patients thought 2g was the maximum recommended single dose; 25% thought that a delay between two doses ≤ 3 hours was recommended and 15% thought the maximum daily dose was > 4 g. While 8% cited liver toxicity as a side effect, 38% did not believe an excessive dose could be fatal. Two patients correctly answered all questions and five gave no correct answer. Outpatients attending an emergency department (ED) have poor knowledge about paracetamol. This situation is disturbing and our results may serve as an eye opener to healthcare professionals. They emphasize the need for research programs with the following objectives: a) to determine the actual content of the message delivered by healthcare professionals; b) to study conditions under which this message is issued; c) to analyze how patients understand key messages and what their behavioral response is. In ED patients, the level of knowledge about paracetamol is insufficient to ensure its safe use in ambulatory care. Further studies are needed to determine the causes and to permit better patient education. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Evaluation of the Analgesic Efficacy of Dexketoprofen Added to Paracetamol.

Science.gov (United States)

Ceyhan, Dilek; Bilir, Ayten; Güleç, Mehmet Sacit

2016-12-01

Multimodal analgesic methods are preferred for the treatment of postoperative pain; as a result, the additive effects of analgesics are provided while probable side effects are avoided. The current study aimed to compare the effects of the combination of dexketoprofen and paracetamol with regard to postoperative pain therapy. Ninety-six patients who underwent non-malignant gynaecological laparotomy operations were included in this study. Patients were randomized into 3 groups. Group D received 50 mg intravenous dexketoprofen 15 minutes before the end of the operation and 8 and 16 hours after the operation. Group P received 1 g intravenous paracetamol and Group DP received the combination of 500 mg paracetamol and 25 mg dexketoprofen at the same time intervals. All patients received morphine infusion after operation. Total morphine consumption at 24 hours, visual analog scale, patient satisfaction and side effects were investigated. Comparison of the visual analog scale scores revealed that the Group DP presented lower scores at 24th hours compared to the other groups; and the difference between Group DP and Group D was statistically significant. Total morphine consumption was not significantly different between the three groups. The minimum number of side effects was observed in the Group DP. Co-administration of paracetamol, dexketoprofen and morphine provided good analgesia and fewer side effects in gynaecological abdominal surgery.

Use of paracetamol, ibuprofen or aspirin in pregnancy and risk of cerebral palsy in the child

DEFF Research Database (Denmark)

Petersen, Tanja Gram; Liew, Zeyan; Nybo Andersen, Anne-Marie

2018-01-01

Background: It has been debated whether mild analgesics, mainly paracetamol, adversely affect aspects of neurodevelopment. We examined whether mother's use of paracetamol, aspirin or ibuprofen in pregnancy is associated with increased risk of cerebral palsy (CP) in the child. Method: We included...... registers. We estimated the average causal effect of analgesics on risk of CP using marginal structural models with stabilized inverse probability weights. Results: Paracetamol use was reported in 49% of all pregnancies, aspirin in 3% and ibuprofen in 4%. Prenatal exposure to paracetamol ever in pregnancy......% CI: 1.0-2.5). Children ever prenatally exposed to aspirin in pregnancy had an elevated risk of bilateral spastic CP (aOR 2.4, 95% CI: 1.1-5.3) compared with unexposed. Conclusion: We observed an increased risk of spastic CP in children prenatally exposed to paracetamol and aspirin. Although we...

Paracetamol use (and/or misuse in children in Enugu, South-East, Nigeria

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Obu Herbert A

2012-07-01

Full Text Available Abstract Background Paracetamol (also known as acetaminophen is the commonest available analgesic and anti-pyretic. It is readily accessed from pharmacy, patent medicine and provision shops as over the counter drug making it a potential drug of abuse, especially in children. We sought to find its use and/or misuse in children seen at the paediatric outpatient clinic of the University of Nigeria Teaching Hospital (UNTH Ituku-Ozalla, Enugu. Objective To determine the dosage, formulation, and frequency of paracetamol administration to children by caregivers and factors associated with its use and/or misuse. Method An observational prospective study involving 231 children and their caregivers seen at the paediatric outpatient clinic of the University of Nigeria Teaching Hospital, Ituku - Ozalla, Enugu between June and November 2011 was undertaken. Data on paracetamol use before presentation to the clinic, in addition to demographic and other data were obtained from the caregivers using a structured questionnaire. Ethical consent for the study was obtained from the Hospital Ethics and Research Committee and informed consent was further obtained from the caregivers of the children. Results A total of 231 children aged six weeks to 16 years and their caregivers participated in this study. The mean ages of the children and their caregivers were 3.8 and 33.9 years, respectively. One hundred and thirty three of the children studied were males while 98 were females. Most of the children (75.6% received paracetamol at home before presenting. Paracetamol tablet alone or in combination with the syrup was mostly used (60% and this observation was made across all age groups. The commonest reason for using paracetamol tablet instead of the syrup was that it was more effective. Most caregivers relied on past experience (71.2% rather than on enclosed information leaflet to decide the appropriate dosage. Half of the children also received other medications

Paracetamol/acetaminophen (single administration) for perineal pain in the early postpartum period.

Science.gov (United States)

Chou, Doris; Abalos, Edgardo; Gyte, Gillian M L; Gülmezoglu, A Metin

2013-01-31

Perineal pain is a common but poorly studied adverse outcome following childbirth. Pain may result from perineal trauma due to bruising, spontaneous tears, surgical incisions (episiotomies), or in association with operative births (ventouse or forceps assisted births). To determine the efficacy of a single administration of paracetamol (acetaminophen) systemic drugs used in the relief of acute postpartum perineal pain We updated the search of the Cochrane Pregnancy and Childbirth Group's Trials Register on 6 November 2012. Randomised controlled trials (RCTs) assessing paracetamol (acetaminophen) in a single dose compared with placebo for women with early postpartum perineal pain. We excluded quasi-RCTs and cross-over studies. Two review authors assessed each paper for inclusion and extracted data. One review author reviewed the decisions and confirmed calculations for pain relief scores. We did not identify any new trials from the updated search so the results remain unchanged as follows.We have included 10 studies describing two dosages of paracetamol. Of these, five studies (526 women) assessed 500 mg to 650 mg and six studies (841 women) assessed 1000 mg of paracetamol. We chose to use random-effects meta-analyses because of the heterogeneity in dosage used. Studies were from the 1970s to the early 1990s, and there was insufficient information to assess the risk of bias adequately, hence the findings need to be interpreted within this context.More women experienced pain relief with paracetamol compared with placebo (average risk ratio (RR) 2.14, 95% confidence interval (CI) 1.59 to 2.89, 10 studies, 1279 women). In addition, there were significantly fewer women having additional pain relief with paracetamol compared with placebo (RR 0.34, 95% CI 0.21 to 0.55, eight studies, 1132 women). Both the 500 mg to 650 mg and 1000 mg doses were effective in providing more pain relief than placebo.Maternal and neonatal potential adverse drug effects were not assessed in

Paracetamol, 3-monoalkyl- and 3,5-dialkyl-substituted derivatives. Antioxidant activity and relationship between lipid peroxidation and cytotoxicity

NARCIS (Netherlands)

Van de Straat, R; Bijloo, G.J.; Vermeulen, N P

1988-01-01

The analgesic drug paracetamol is known to cause lipid peroxidation and hepatotoxicity after overdosage. In this paper, the relationship between lipid peroxidation and toxicity in freshly isolated hepatocytes was studied using paracetamol and three 3-monoalkyl-substituted derivatives of paracetamol.

A population-based study of salivary lysozyme concentrations and candidal counts.

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Yeh, C K; Dodds, M W; Zuo, P; Johnson, D A

1997-01-01

The relationship between salivary lysozyme concentration and oral candida load was examined in 595 adults. Unstimulated whole saliva, and citrate-stimulated parotid and submandibular/sublingual saliva were collected from each participant. Candida colony-forming units (c.f.u.) in unstimulated whole saliva were determined. An enzyme-linked immunosorbent assay for lysozyme using commercially available antibodies was developed. This assay showed a linear relation of salivary lysozyme concentrations from 0.5 to 4.0 ng/ml. Significant negative relations were observed between lysozyme concentration and flow rate: r = -0.16 (p candida counts (r = 0.18: p candida in whole saliva revealed that lysozyme concentrations were higher in the high candida (> or = 1000 c.f.u./ml) group than in the zero and moderate candida categories in stimulated parotid saliva (p candida load increases.

Real-time PCR quantification of six periodontal pathogens in saliva samples from healthy young adults.

Science.gov (United States)

Zhou, Xiaodong; Liu, Xiaoli; Li, Jing; Aprecio, Raydolfo M; Zhang, Wu; Li, Yiming

2015-05-01

The use of saliva as a diagnostic fluid for the evaluation of periodontal health has gained attention recently. Most published real-time PCR assays focused on quantification of bacteria in subgingival plaque, not in saliva. The aims of this study were to develop a real-time PCR assay for quantification of six periodontal pathogens in saliva and to establish a relationship between the amount of DNA (fg) and colony-forming unit (CFU). TaqMan primers/probe sets were used for the detection of Aggregatibacter actinomycetemcomitans (Aa), Eikenella corrodens (Ec), Fusobacterium nucleatum (Fn), Porphyromonas gingivalis (Pg), Prevotella intermedia (Pi), Tannerella forsythia (Tf), and total bacteria. Six periodontal pathogens and total bacteria in saliva from 24 periodontally healthy individuals were determined. The relationship between the amount of DNA (fg) and CFU was established by measuring the concentrations of extracted bacterial DNA and CFU per milliliter of bacteria on agar plates. Fn, Ec, and Pi were detected in all saliva samples, while 58.5, 45.8, and 33.3% were detected for Tf, Pg, and Aa, respectively. Numbers of Ec and Fn in saliva were highly correlated (R(2) = 0.93, P periodontal pathogens in saliva and estimate the number of live bacteria (CFU). This real-time PCR assay in combination with the relationship between DNA (fg) and CFU has the potential to be an adjunct in evaluation of periodontal health status.

Intraocular pressure-lowering effect of oral paracetamol and its in vitro corneal penetration properties

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Mohamed N

2013-01-01

Full Text Available Nabiel Mohamed, David MeyerDivision of Ophthalmology, Faculty of Medicine and Health Sciences, University of Stellenbosch, Cape Town, South AfricaBackground: Several studies have confirmed the ability of cannabinoids to reduce intraocular pressure. Experimental data recently demonstrated unequivocally that the analgesic effect of paracetamol is due to its indirect action on cannabinoid receptors. The question then arises as to whether paracetamol can reduce intraocular pressure via its effect on intraocular cannabinoid receptors.Methods: A 2-week, prospective, randomized, controlled, single-center, parallel-group pilot study was carried out to determine the efficacy and safety of paracetamol 1 g orally administered every 6 hours in adult patients with primary or secondary open angle glaucoma as compared with topical levobunolol 0.5% twice a day. Patient well-being was closely monitored throughout the study and focused on hepatic safety in accordance with Drug-Induced Liver Injury Network criteria. The in vitro diffusion kinetics of acetaminophen in a phosphate-buffered solution in rabbit and human corneas was also investigated, with the view to a topical application.Results: Eighteen adult patients were enrolled in the study, with nine in the topical levobunolol group and nine in the oral paracetamol group. In the levobunolol group, the mean reduction in intraocular pressure at day 7 was 7.5 mmHg (P < 0.008 and at day 14 was 9.1 mmHg (P < 0.005, from a mean baseline intraocular pressure of 29.6 mmHg. The corresponding figures for the paracetamol group were 8.8 mmHg (P < 0.0004 at day 7 and 6.5 mmHg (P < 0.004 at day 14, from a mean baseline intraocular pressure of 29.4 mmHg. Both study regimens were well tolerated. No serious treatment-related adverse events were reported in either of the treatment groups. Liver function tests, systolic/diastolic blood pressure, or heart rate remained unchanged in both groups during the 2 weeks of the study. In

White Light Generation in Human Saliva

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Santhosh, C.; Dharmadhikari, A. K.; Dharmadhikari, J. A.; Alti, K.; Mathur, D.

2011-07-01

Interaction of intense, femto-second pulses of infrared light (800 nm) with water generates white light supercontinuum due to nonlinear optical effects. This supercontinuum was found to be suppressed by the addition of alpha amylase, a major protein in the human saliva. We have studied the suppression of supper continuum by human saliva, collected from healthy subjects with and without smoking habits. Suppression of the blue-sided components was observed significantly in non-smokers saliva than chain smokers.

Dexketoprofen-induced antinociception in animal models of acute pain: synergy with morphine and paracetamol.

Science.gov (United States)

Miranda, Hugo F; Puig, Margarita M; Dursteler, Christian; Prieto, Juan Carlos; Pinardi, Gianni

2007-02-01

The antinociceptive activity of dexketoprofen was studied in mice using the acetic acid writhing test (acute tonic pain), the tail flick test (acute phasic pain) and the formalin assay (inflammatory pain). Isobolographic analysis was used to study the antinociceptive interactions between morphine and paracetamol co-administered with dexketoprofen. In the writhing test, the intraperitoneal administration of dexketoprofen or ketoprofen resulted in parallel dose-response curves with equal efficacy, but higher relative potency for dexketoprofen. In the tail flick test, the curves were parallel with similar efficacy and potency. The administration of morphine or paracetamol in both tests resulted in dose-response curves not parallel with that of dexketoprofen, which showed a potency between morphine and paracetamol. In the formalin assay, the antinociceptive activity of morphine during phase I was 122, 295 and 1695 times higher than dexketoprofen, ketoprofen and paracetamol, respectively. Isobolographic analysis demonstrated that the combination of sub-analgesic doses of dexketoprofen with morphine or with paracetamol was strongly synergic in all three tests. Synergistic drug combinations should improve effective pharmacological treatment of pain, minimizing drug specific adverse effects. These findings are undoubtedly worthy of additional controlled clinical trials in severe pain syndromes.

Perinatal paracetamol exposure in mice does not affect the development of allergic airways disease in early life

Science.gov (United States)

Lee, Debbie C P; Walker, Simone A; Byrne, Adam J; Gregory, Lisa G; Buckley, James; Bush, Andrew; Shaheen, Seif O; Saglani, Sejal; Lloyd, Clare M

2015-01-01

Background Current data concerning maternal paracetamol intake during pregnancy, or intake during infancy and risk of wheezing or asthma in childhood is inconclusive based on epidemiological studies. We have investigated whether there is a causal link between maternal paracetamol intake during pregnancy and lactation and the development of house dust mite (HDM) induced allergic airways disease (AAD) in offspring using a neonatal mouse model. Methods Pregnant mice were administered paracetamol or saline by oral gavage from the day of mating throughout pregnancy and/or lactation. Subsequently, their pups were exposed to intranasal HDM or saline from day 3 of life for up to 6 weeks. Assessments of airway hyper-responsiveness, inflammation and remodelling were made at weaning (3 weeks) and 6 weeks of age. Results Maternal paracetamol exposure either during pregnancy and/or lactation did not affect development of AAD in offspring at weaning or at 6 weeks. There were no effects of maternal paracetamol at any time point on airway remodelling or IgE levels. Conclusions Maternal paracetamol did not enhance HDM induced AAD in offspring. Our mechanistic data do not support the hypothesis that prenatal paracetamol exposure increases the risk of childhood asthma. PMID:25841236

Risk factors in the development of adverse reactions to N-acetylcysteine in patients with paracetamol poisoning

DEFF Research Database (Denmark)

Schmidt, L E; Dalhoff, K

2001-01-01

AIMS: To identify risk factors in the development of side-effects to N-acetylcysteine (NAC) in patients with paracetamol poisoning. METHODS: A retrospective study was carried out based upon the hospital charts of 529 consecutive patients admitted with paracetamol poisoning, all treated with NAC...... 2.9 times (95% CI 2.1, 4.7) more likely to develop side-effects (Chi-square: P = 0.004). Side-effects were of similar severity in asthmatics and nonasthmatics. A history of medical allergy was not a risk factor. Serum paracetamol was lower in patients with side-effects than in those without (Mann......-Whitney: P = 0.00006). CONCLUSIONS: Asthma must be considered a risk factor in the development of side-effects to NAC. However, the side-effects are easily managed and there is no reason to withhold NAC from any patient with paracetamol poisoning. Paracetamol itself seems to offer some protection against...

Relationship of serum and saliva calcium, phosphorus and alkaline phosphatase with dry mouth feeling in menopause.

Science.gov (United States)

Agha-Hosseini, Farzaneh; Mirzaii-Dizgah, Iraj; Moosavi, Mahdieh-Sadat

2012-06-01

The aim of this study was to compare serum and saliva calcium, phosphorus and alkaline phosphatase of menopausal women with/without dry mouth (DM) feeling. The composition of saliva in menopause women with/without DM feeling is different. Some of these differences are in hormones that are related to bone turnover. A case-control study was carried out on 60 selected menopausal women aged 45-79 years with or without DM feeling (30 as case, 30 as control), conducted at the Clinic of Oral Medicine, Tehran University of Medical Sciences. The phosphorus concentration was measured by photometrical measurement of the blue colour formed after the addition of ammonium molybdate and stannous chloride; calcium was measured by Arsenazo reaction; and alkaline phosphatase by the pNPP-AMP method. Statistical analysis of Student's t-test was used. The mean serum phosphorus and alkaline phosphatase, stimulated and unstimulated saliva calcium and alkaline phosphatase levels were significantly higher in the menopausal women suffering from DM. There were no significant differences between groups regarding saliva phosphorus and serum calcium concentration. Calcium, phosphorus and alkaline phosphatase appear associated with DM feeling in menopause. © 2012 The Gerodontology Society and John Wiley & Sons A/S.

Wel of geen paracetamol bij kinderen met koorts? [Risks and benefits of paracetamol in children with fever

NARCIS (Netherlands)

de Bont, E.G.P.M.; Brand, P.L.P.; Dinant, G.J.; van Well, G.T.J.; Cals, J.W.L.

2014-01-01

Worldwide, paracetamol is the most commonly used antipyretic for children and the drug of first choice for reducing fever named in the majority of practice guidelines. However, whether or not it is necessary or desirable to treat fever is questionable. The provision of accurate information on the

Combining paracetamol (acetaminophen) with nonsteroidal antiinflammatory drugs: a qualitative systematic review of analgesic efficacy for acute postoperative pain.

Science.gov (United States)

Ong, Cliff K S; Seymour, Robin A; Lirk, Phillip; Merry, Alan F

2010-04-01

There has been a trend over recent years for combining a nonsteroidal antiinflammatory drug (NSAID) with paracetamol (acetaminophen) for pain management. However, therapeutic superiority of the combination of paracetamol and an NSAID over either drug alone remains controversial. We evaluated the efficacy of the combination of paracetamol and an NSAID versus either drug alone in various acute pain models. A systematic literature search of Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, and PubMed covering the period from January 1988 to June 2009 was performed to identify randomized controlled trials in humans that specifically compared combinations of paracetamol with various NSAIDs versus at least 1 of these constituent drugs. Identified studies were stratified into 2 groups: paracetamol/NSAID combinations versus paracetamol or NSAIDs. We analyzed pain intensity scores and supplemental analgesic requirements as primary outcome measures. In addition, each study was graded for quality using a validated scale. Twenty-one human studies enrolling 1909 patients were analyzed. The NSAIDs used were ibuprofen (n = 6), diclofenac (n = 8), ketoprofen (n = 3), ketorolac (n = 1), aspirin (n = 1), tenoxicam (n = 1), and rofecoxib (n = 1). The combination of paracetamol and NSAID was more effective than paracetamol or NSAID alone in 85% and 64% of relevant studies, respectively. The pain intensity and analgesic supplementation was 35.0% +/- 10.9% and 38.8% +/- 13.1% lesser, respectively, in the positive studies for the combination versus paracetamol group, and 37.7% +/- 26.6% and 31.3% +/- 13.4% lesser, respectively, in the positive studies for the combination versus the NSAID group. No statistical difference in median quality scores was found between experimental groups. Current evidence suggests that a combination of paracetamol and an NSAID may offer superior analgesia compared with either drug alone.

Fever and the use of paracetamol during IL-2-based immunotherapy in metastatic melanoma

DEFF Research Database (Denmark)

Køstner, Anne Helene; Ellegaard, Mai-Britt Bjørklund; Christensen, Ib Jarle

2015-01-01

effective antitumor immune response. The purpose of this retrospective study was to examine the potential role of the IL-2-induced fever in melanoma patients treated with or without paracetamol in two consecutive cohorts. One hundred and seventy-nine patients with metastatic melanoma treated with a modified...... decrescendo regimen of IL-2 and Interferon (IFN) between 2004 and 2010 were retrospectively studied. 87 patients treated before 2007 received paracetamol as part of the treatment schedule, and 92 patients treated after 2007 did not receive paracetamol routinely. Body temperature was analyzed as dichotomized...

Radioimmunological analysis of circadian rhythms of cortisol and melatonin in saliva

International Nuclear Information System (INIS)

Demel, A.W.

1990-12-01

Since blood cortisol (F) and melatonin (MLT) display a circadian secretion pattern and since the saliva concentration of this hormones is an excellent indicator of its blood levels the measurement of salivary F and MLT may be user for examining circadian rhythmicity. In this study the relationship between salivary F and MLT was explored. For this purpose it was necessary first to establish and validate a radioimmunoassay for F in saliva: salivary F was determined by a direct radioimmunoassay using cortisol-3-(O-carb oxymethyl) oximino-(2-( 125 I)iodohistamin) as tracer and cortisol-3-CMO-BSA antiserum. The parallel measurement of F levels in saliva and serum of adults gave an excellent correlation (r=0.87, p 0.00956x ). Serum F was assayed on the Abott TDX-System using a radioimmunofluorescence method. Secondly, using this assay the circadian saliva F pattern was determined as well as the pattern of salivary MLT in 9 young, healthy volunteers. For saliva MLT estimations a previously published method was applied (SCHULZ et al 1990). Using a computerized program (RHYTHM) written by EVE v. CAUTER (1979), the hormone data of each individuum were examined for circadian rhythmicity and its acrophase (time of occurence of the maximum of a sinusoid fitted to the data). The F acrophase occured between 7:00 and 12:00 h (Mean: 3:33 h, SD: 104.4 min). The easy stress-free non invasive nature of saliva collection makes saliva to one of the most accessible body fluids and of high value in studying the circadian system in healthy humans as well as in infants, children, pregnant women and anaemic patients. Measurements of salivary F and MLT may help to elucidate not only the circadian rhythms of these hormones under normal and pathological conditions but it may also provide insight in physiology and pathology of the circadian system in general. (author)

Predicting Transport of 3,5,6-Trichloro-2-Pyridinol Into Saliva Using a Combination Experimental and Computational Approach

Energy Technology Data Exchange (ETDEWEB)

Smith, Jordan Ned; Carver, Zana A.; Weber, Thomas J.; Timchalk, Charles

2017-04-11

A combination experimental and computational approach was developed to predict chemical transport into saliva. A serous-acinar chemical transport assay was established to measure chemical transport with non-physiological (standard cell culture medium) and physiological (using surrogate plasma and saliva medium) conditions using 3,5,6-trichloro-2-pyridinol (TCPy) a metabolite of the pesticide chlorpyrifos. High levels of TCPy protein binding was observed in cell culture medium and rat plasma resulting in different TCPy transport behaviors in the two experimental conditions. In the non-physiological transport experiment, TCPy reached equilibrium at equivalent concentrations in apical and basolateral chambers. At higher TCPy doses, increased unbound TCPy was observed, and TCPy concentrations in apical and basolateral chambers reached equilibrium faster than lower doses, suggesting only unbound TCPy is able to cross the cellular monolayer. In the physiological experiment, TCPy transport was slower than non-physiological conditions, and equilibrium was achieved at different concentrations in apical and basolateral chambers at a comparable ratio (0.034) to what was previously measured in rats dosed with TCPy (saliva:blood ratio: 0.049). A cellular transport computational model was developed based on TCPy protein binding kinetics and accurately simulated all transport experiments using different permeability coefficients for the two experimental conditions (1.4 vs 0.4 cm/hr for non-physiological and physiological experiments, respectively). The computational model was integrated into a physiologically based pharmacokinetic (PBPK) model and accurately predicted TCPy concentrations in saliva of rats dosed with TCPy. Overall, this study demonstrates an approach to predict chemical transport in saliva potentially increasing the utility of salivary biomonitoring in the future.

Population Pharmacokinetics of Intravenous Paracetamol (Acetaminophen) in Preterm and Term Neonates: Model Development and External Evaluation.

Science.gov (United States)

Cook, Sarah F; Roberts, Jessica K; Samiee-Zafarghandy, Samira; Stockmann, Chris; King, Amber D; Deutsch, Nina; Williams, Elaine F; Allegaert, Karel; Wilkins, Diana G; Sherwin, Catherine M T; van den Anker, John N

2016-01-01

The aims of this study were to develop a population pharmacokinetic model for intravenous paracetamol in preterm and term neonates and to assess the generalizability of the model by testing its predictive performance in an external dataset. Nonlinear mixed-effects models were constructed from paracetamol concentration-time data in NONMEM 7.2. Potential covariates included body weight, gestational age, postnatal age, postmenstrual age, sex, race, total bilirubin, and estimated glomerular filtration rate. An external dataset was used to test the predictive performance of the model through calculation of bias, precision, and normalized prediction distribution errors. The model-building dataset included 260 observations from 35 neonates with a mean gestational age of 33.6 weeks [standard deviation (SD) 6.6]. Data were well-described by a one-compartment model with first-order elimination. Weight predicted paracetamol clearance and volume of distribution, which were estimated as 0.348 L/h (5.5 % relative standard error; 30.8 % coefficient of variation) and 2.46 L (3.5 % relative standard error; 14.3 % coefficient of variation), respectively, at the mean subject weight of 2.30 kg. An external evaluation was performed on an independent dataset that included 436 observations from 60 neonates with a mean gestational age of 35.6 weeks (SD 4.3). The median prediction error was 10.1 % [95 % confidence interval (CI) 6.1-14.3] and the median absolute prediction error was 25.3 % (95 % CI 23.1-28.1). Weight predicted intravenous paracetamol pharmacokinetics in neonates ranging from extreme preterm to full-term gestational status. External evaluation suggested that these findings should be generalizable to other similar patient populations.

A simple high-performance liquid chromatography for the determination of linezolid in human plasma and saliva.

Science.gov (United States)

Hara, Shuuji; Uchiyama, Masanobu; Yoshinari, Masami; Matsumoto, Taichi; Jimi, Shiro; Togawa, Atsushi; Takata, Tohru; Takamatsu, Yasushi

2015-09-01

Linezolid is an antimicrobial agent for the treatment of multiresistant Gram-positive infections. A practical high-performance liquid chromatography method was developed for the determination of linezolid in human plasma and saliva. Linezolid and an internal standard (o-ethoxybenzamide) were extracted from plasma and saliva with ethyl acetate and analyzed on a Capcell Pak C18 MG column with UV detection at 254 nm. The calibration curve was linear through the range 0.5-50 µg/mL using a 200 μL sample volume. The intra- and interday precisions were all plasma and 5.60% for saliva. The accuracies ranged from 98.8 to 110% for both matrices. The mean recoveries of linezolid were 80.8% for plasma and 79.0% for saliva. This method was used to determine the plasma and saliva concentrations of linezolid in healthy volunteers who were orally administered a 600 mg dose of linezolid. Our liquid-liquid extraction procedure is easy and requires a small volume of plasma or saliva (200 μL). This small volume can be advantageous in clinical pharmacokinetic studies, especially if children participate. Copyright © 2015 John Wiley & Sons, Ltd.

The functions of human saliva

DEFF Research Database (Denmark)

Dawes, C; Pedersen, Anne Marie Lynge; Villa, A

2015-01-01

This narrative review of the functions of saliva was conducted in the PubMed, Embase and Web of Science databases. Additional references relevant to the topic were used, as our key words did not generate references which covered all known functions of saliva. These functions include maintaining a...... of oral wounds. Clearly, saliva has many functions which are needed for proper protection and functioning of the human body....... a moist oral mucosa which is less susceptible to abrasion, and removal of micro-organisms, desquamated epithelial cells, leucocytes and food debris by swallowing. The mucins form a slimy coating on all surfaces in the mouth and act as a lubricant during such processes as mastication, formation of a food...

Cortisol in urine and saliva

DEFF Research Database (Denmark)

Hurwitz Eller, N; Netterstrøm, B; Hansen, Åse Marie

2001-01-01

The objective of the study was to analyse the relations between excretion of cortisol in urine and saliva and the intima media thickness (IMT) of the artery carotis communis.......The objective of the study was to analyse the relations between excretion of cortisol in urine and saliva and the intima media thickness (IMT) of the artery carotis communis....

Retrospective study of paracetamol poisoning in children aged zero to six years found no cases of liver injury

DEFF Research Database (Denmark)

Dan-Nielsen, S; Bisgaard, A S; Jans, S R

2018-01-01

AIM: This study focused on children aged zero to six years with suspected single-dose paracetamol poisoning, which has not been investigated in Denmark. We evaluated the incidence of liver injuries and the use of activated charcoal and N-acetylcysteine treatment. METHODS: Our retrospective study.......67 ± 1.05 years. Activated charcoal treatment was given in 87% of cases, but only 15% of the children received treatment within one hour of the suspected paracetamol poisoning. Although 80% of the children received N-acetylcysteine treatment, only one case (0.5%) had a toxic plasma paracetamol level...... children aged zero to six years with suspected paracetamol poisoning. Vomiting or abdominal pain was associated with elevated plasma paracetamol levels. No liver injuries were reported....

Worldwide research productivity of paracetamol (acetaminophen) poisoning: a bibliometric analysis (2003-2012).

Science.gov (United States)

Zyoud, S H; Al-Jabi, S W; Sweileh, W M

2015-01-01

There is a lack of data concerning the evaluation of scientific research productivity in paracetamol poisoning from the world. The purposes of this study were to analyse the worldwide research output related to paracetamol poisoning and to examine the authorship pattern and the citations retrieved from the Scopus database for over a decade. Data were searched for documents with specific words regarding paracetamol poisoning as 'keywords' in the title or/and abstract. Scientific output was evaluated based on a methodology developed and used in other bibliometric studies. Research productivity was adjusted to the national population and nominal gross domestic product (GDP) per capita. There were 1721 publications that met the criteria during study period from the world. All retrieved documents were published from 72 countries. The largest number of articles related to paracetamol poisoning was from the United States (US; 30.39%), followed by India (10.75%) and the United Kingdom (UK; 9.36%). The total number of citations at the time of data analysis was 21,109, with an average of 12.3 citations per each documents and median (interquartile range) of 4 (1-14). The h-index of the retrieved documents was 57. After adjusting for economy and population power, India (124.2), Nigeria (18.6) and the US (10.5) had the highest research productivity. Countries with large economies, such as the UK, Australia, Japan, China and France, tended to rank relatively low after adjustment for GDP over the entire study period. Our study demonstrates evidence that research productivity related to paracetamol poisoning has increased rapidly during the recent years. The US obviously dominated in research productivity. However, certain smaller country such as Nigeria has high scientific output relative to their population size and GDP. A highly noticeable increase in the contributions of Asia-Pacific and Middle East regions to scientific literature related to paracetamol poisoning was also

Recuperación de veillonellas a partir de saliva Recovery of Veillonella from saliva

Directory of Open Access Journals (Sweden)

M.I. Gutiérrez De Ferro

2005-03-01

Full Text Available Las veillonellas son cocos gram-negativos anaerobios asociados con salud oral. Para su aislamiento, se han reportado diferentes medios de cultivo. Las colonias de Veillonella spp. producen fluorescencia roja visible con luz ultravioleta, que desaparece en contacto con oxígeno. Esta propiedad sería útil para su identificación presuntiva rápida. Los objetivos de este trabajo fueron: 1- comparar el medio selectivo para Veillonella de Rogosa con los medios de cultivo recomendados por diferentes autores para determinar en cual de ellos se obtiene una mejor recuperación de veillonellas a partir de saliva, ya que esta muestra es generalmente utilizada para determinar la presencia y predominio de esta bacteria; 2- detectar la producción de fluorescencia en estos medios de cultivo como método rápido de identificación. Los medios de cultivo estudiados fueron: medio selectivo para Veillonella, agar Schaedler para anaerobios con vitamina K, agar tioglicolato, agar infusión cerebro corazón, agar Brucella, agar tripteína soja y agar Columbia con y sin el agregado de vancomicina y sangre lacada. La muestra ensayada fue un pool de saliva. Se hicieron recuentos de colonias de veillonellas y de microorganismos totales expresados en UFC/ml de saliva. La mayor recuperación de veillonellas en saliva se obtuvo en el medio selectivo para Veillonella con vancomicina y sangre lacada. Sólo se observó producción de fluorescencia en este medio.Veillonella spp. are anaerobic gram-negative cocci associated to oral health. Different types of cultures have been reported for the isolation of these microorganisms. Veillonella spp. colonies produce a red fluorescence, which is made visible through ultraviolet light and disappears in contact with oxygen. This feature would be very useful for rapid presumptive identification. The aims of this study were: 1. to compare the Rogosa selective medium for Veillonella with the cultures recommended by different authors in

[Effect of paracetamol (acetaminophen) on blood pressure in patients with coronary heart disease].

Science.gov (United States)

Sudano, I; Roas, S; Flammer, A J; Noll, G; Ruschitzka, F

2012-06-06

Analgesic drugs, non-steroidal anti-inflammatory drugs and paracetamol (acetaminophen) in particular, belong to the most widely prescribed therapeutic agents. Beside their efficacy in pain relief, these drugs were recently linked to increased cardiovascular risk. Indeed, epidemiological and clinical studies showed that non-selective non-steroidal anti-inflammatory drugs, as well as selective cyclooxygenase-2 inhibitors both may increase blood pressure and cardiovascular events. However, the effect of paracetamol (acetaminophen) on blood pressure and cardiovascular health should not be neglected, too. Unfortunately, long-term randomized controlled trials appropriately powered to evaluate cardiovascular outcomes are lacking. This review summarizes the available data about the effect of paracetamol in particular, on blood pressure and other cardiovascular outcomes.

Salivary flow rate and biochemical composition analysis in stimulated whole saliva of children with cystic fibrosis.

Science.gov (United States)

da Silva Modesto, Karine Barros; de Godói Simões, Jéssica Bueno; de Souza, Amanda Ferreira; Damaceno, Neiva; Duarte, Danilo Antonio; Leite, Mariana Ferreira; de Almeida, Eliete Rodrigues

2015-11-01

It is recognized that cystic fibrosis (CF) patients present a risk for oral diseases, since it affects exocrine glands, and the treatment consists of a carbohydrate-rich diet. Recognizing the protective function of saliva on maintaining oral health, the aim of the study was to evaluate salivary parameters in stimulated whole saliva from children with CF. A case-control study was conducted comparing stimulated whole saliva of healthy (n=28; control group) and CF children (n=21; experimental group). Salivary flow rate, initial pH, buffer capacity (total and in each range of pH), total protein and sialic acid (total, free, and conjugated) concentration, α-amylase and salivary peroxidase activities were evaluated. Data were compared by two-tailed Student t test (95% CI; p ≤ 0.05). CF patients presented a significant reduction in salivary parameters compared with the control group (p ≤ 0.05): salivary flow rate (36%), buffer capacity (pH range from 6.9 to 6.0), sialic acid concentration (total 75%, free 61%, and conjugated 83%); α-amylase and salivary peroxidase activities (55%). Additionally, a significant increase in total protein concentration (180%) of stimulated whole saliva from CF patients was verified compared with the control group (p ≤ 0.05). Children with CF presented significant changes in salivary composition, including salivary flow rate, buffering capacity and protective proteins of the oral cavity, compared with children without CF. Copyright © 2015 Elsevier Ltd. All rights reserved.

Analgesic efficacy and safety of intravenous paracetamol (acetaminophen) administered as a 2g starting dose following third molar surgery

DEFF Research Database (Denmark)

Juhl, Gitte Irene; Nørholt, Sven E.; Tønnesen, Else Kirstine

2006-01-01

BACKGROUND: The recommended dose for intravenous (IV) paracetamol injection in adults is 1g, however pharmacokinetic and pharmacodynamic findings suggest that a better analgesia could be obtained with a 2g starting dose. METHODS: A single-centre, randomised, double-blind, placebo-controlled, 3......-parallel group study was performed to demonstrate the analgesic efficacy and safety of IV paracetamol 2g. Following third molar surgery, patients reporting moderate to severe pain received a single 15-min infusion of either IV paracetamol 2g, IV paracetamol 1g or placebo. Efficacy and safety were evaluated...... over 8h. Laboratory tests were performed before and 48h after drug administration. RESULTS: Two hundred and ninety seven patients (132=IV paracetamol 2g; 132=IV paracetamol 1g; 33=placebo) were randomised and completed the study. The summed pain relief over 6h (TOTPAR6) was significantly superior...

PACE - The first placebo controlled trial of paracetamol for acute low back pain: design of a randomised controlled trial

Directory of Open Access Journals (Sweden)

Day Richard O

2010-07-01

Full Text Available Abstract Background Clinical practice guidelines recommend that the initial treatment of acute low back pain (LBP should consist of advice to stay active and regular simple analgesics such as paracetamol 4 g daily. Despite this recommendation in all international LBP guidelines there are no placebo controlled trials assessing the efficacy of paracetamol for LBP at any dose or dose regimen. This study aims to determine whether 4 g of paracetamol daily (in divided doses results in a more rapid recovery from acute LBP than placebo. A secondary aim is to determine if ingesting paracetamol in a time-contingent manner is more effective than paracetamol taken when required (PRN for recovery from acute LBP. Methods/Design The study is a randomised double dummy placebo controlled trial. 1650 care seeking people with significant acute LBP will be recruited. All participants will receive advice to stay active and will be randomised to 1 of 3 treatment groups: time-contingent paracetamol dose regimen (plus placebo PRN paracetamol, PRN paracetamol (plus placebo time-contingent paracetamol or a double placebo study arm. The primary outcome will be time (days to recovery from pain recorded in a daily pain diary. Other outcomes will be pain intensity, disability, function, global perceived effect and sleep quality, captured at baseline and at weeks 1, 2, 4 and 12 by an assessor blind to treatment allocation. An economic analysis will be conducted to determine the cost-effectiveness of treatment from the health sector and societal perspectives. Discussion The successful completion of the trial will provide the first high quality evidence on the effectiveness of the use of paracetamol, a guideline endorsed treatment for acute LBP. Trail registration ACTRN12609000966291.

Effect of a herbal extract containing curcumin and piperine on midazolam, flurbiprofen and paracetamol (acetaminophen) pharmacokinetics in healthy volunteers

Science.gov (United States)

Volak, Laurie P; Hanley, Michael J; Masse, Gina; Hazarika, Suwagmani; Harmatz, Jerold S; Badmaev, Vladimir; Majeed, Muhammed; Greenblatt, David J; Court, Michael H

2013-01-01

Aims Turmeric extract derived curcuminoids (curcumin, demethoxycurcumin and bisdemethoxycurcumin) are currently being evaluated for the treatment of cancer and Alzheimer's dementia. Previous in vitro studies indicate that curcuminoids and piperine (a black pepper derivative that enhances curcuminoid bioavailability) could inhibit human CYP3A, CYP2C9, UGT and SULT dependent drug metabolism. The aim of this study was to determine whether a commercially available curcuminoid/piperine extract alters the pharmacokinetic disposition of probe drugs for these enzymes in human volunteers. Methods A randomized placebo-controlled six way crossover study was conducted in eight healthy volunteers. A standardized curcuminoid/piperine preparation (4 g curcuminoids plus 24 mg piperine) or matched placebo was given orally four times over 2 days before oral administration of midazolam (CYP3A probe), flurbiprofen (CYP2C9 probe) or paracetamol (acetaminophen) (dual UGT and SULT probe). Plasma and urine concentrations of drugs, metabolites and herbals were measured by HPLC. Subject sedation and electroencephalograph effects were also measured following midazolam dosing. Results Compared with placebo, the curcuminoid/piperine treatment produced no meaningful changes in plasma Cmax, AUC, clearance, elimination half-life or metabolite levels of midazolam, flurbiprofen or paracetamol (α = 0.05, paired t-tests). There was also no effect of curcuminoid/piperine treatment on the pharmacodynamics of midazolam. Although curcuminoid and piperine concentrations were readily measured in plasma following glucuronidase/sulfatase treatment, unconjugated concentrations were consistently below the assay thresholds (0.05–0.08 μm and 0.6 μm, respectively). Conclusion The results indicate that short term use of this piperine-enhanced curcuminoid preparation is unlikely to result in a clinically significant interaction involving CYP3A, CYP2C9 or the paracetamol conjugation enzymes. PMID:22725836

High-Pressure High-Temperature Phase Diagram of the Organic Crystal Paracetamol

Science.gov (United States)

Smith, Spencer; Montgomery, Jeffrey; Vohra, Yogesh

High-pressure high-temperature (HPHT) Raman spectroscopy studies have been performed on the organic crystal paracetamol in a diamond anvil cell utilizing boron-doped diamond as heating anvil. The HPHT data obtained from boron-doped diamond heater is cross-checked with data obtained using a standard block heater diamond anvil cell. Isobaric measurements were conducted at pressures up to 8.5 GPa and temperature up to 520 K in a number of different experiments. Solid state phase transitions from monoclinic Form I --> orthorhombic Form II were observed at various pressures and temperatures as well as transitions from Form II --> unknown Form IV. The melting temperature for paracetamol was observed to increase with increasing pressures to 8.5 GPa. Our previous angle dispersive x-ray diffraction studies at the Advanced Photon Source has confirmed the existence of two unknown crystal structures Form IV and Form V of paracetamol at high pressure and ambient temperature. The phase transformation from Form II to Form IV occurs at ~8.5 GPa and from Form IV to Form V occurs at ~11 GPa at ambient temperature. Our new data is combined with the previous ambient temperature high-pressure Raman and X- ray diffraction data to create the first HPHT phase diagram of paracetamol. Doe-NNSA Carnegie DOE Alliance Center (CDAC) under Grant Number DE-NA0002006.

Pre-natal exposure to paracetamol and risk of wheezing and asthma in children: A birth cohort study

DEFF Research Database (Denmark)

Rebordosa, Cristina; Kogevinas, Manolis; Sørensen, Henrik T

2008-01-01

BACKGROUND: Paracetamol use has been associated with increased prevalence of asthma in children and adults, and one study reported an association between pre-natal exposure to paracetamol and asthma in early childhood. METHODS: To examine if pre-natal exposure to paracetamol is associated...... with the risk of asthma or wheezing in early childhood, we selected 66 445 women from the Danish National Birth Cohort for whom we had information on paracetamol use during pregnancy and who participated in an interview when their children were 18-months-old and 12 733 women whose children had reached the age...... of 7 and estimated the prevalence of physician-diagnosed asthma and wheezing at the ages of 18 months and 7 years. We also linked our population to the Danish National Hospital Registry to record all hospitalizations due to asthma up to age of 18 months. RESULTS: Paracetamol use during any time...

Comparison of Patient-Controlled Analgesia Using Morphine With and Without Paracetamol in Postoperative Pain Control

Directory of Open Access Journals (Sweden)

Mehryar Taghavi Gilani

2016-04-01

Full Text Available Introduction: Postoperative pain control plays a pivotal role in reducing postoperative complications, hospitality time, and increasing satisfaction. This study aimed to evaluate the effect of paracetamol on the pain and complications caused by gastrectomy. Materials and Methods: This randomized prospective study was conducted on 60 patients (two same group who were candidate for gastrectomy in Imam Reza Hospital of Mashhad, Iran during August-September 2015. The first group received Patient-Controlled Analgesia (PCA with morphine only, and in the second group, paracetamol (1 gram infused with morphine every six hours. Level of pain, morphine intake, and side effects were evaluated in both groups. Results:No significant difference was observed in the four-scale score of pain in the patients (morphine group: 0.64±0.1, morphine-paracetamol group: 0.6±0.1 (P=0.72. During the first 24 hours after the surgery, the morphine group had lower consciousness level (2.3±0.2 compared to the morphine-paracetamol group (1.7±0.3 (P=0.001. Moreover, infusion of paracetamol with morphine to control the pain after gastrectomy reduced the need for morphine analgesia. Morphine intake was 21.4±7.7 in morphine group, while it was 14.3±5.8 in the morphine-paracetamol group within the first 24 hours after the surgery (P=0.001. However, this level had no significant effect on postoperative complications such as itching, nausea, and arterial oxygen saturation. Conclusion: According to the results of this study, intravenous paracetamol (one gram administered every six hours with PCA using morphine could decrease morphine intake leading to better consciousness level during the first 24 hours after gastrectomy without further complications.

Parámetros inflamatorios en saliva y sangre en niños y adolescentes sanos Inflammatory parameters in saliva and blood from healthy children and adolescents

Directory of Open Access Journals (Sweden)

Ninoska Tahis Viera Sirit

2011-09-01

como fluido corporal que permita sustituir la determinación sérica de IL-1, IL-6 y sustancias reactivas al ácido tiobarbitúrico. En cuanto al TNF-a se evidenció una correlación significativa, lo cual podría plantear la posible sustitución de muestras séricas por salivales.At present times, there is interest in the use of saliva as a diagnosis, prediction and progression alternative of different pathologies in relation to the body fluids. To correlate the concentrations of IL-1, IL-6, TNF-a, substances reactive to thiobarbituric acid (RSTBA and O2- in the saliva and blood of systematically healthy children and adolescents. A cross-sectional study was performed in 23 healthy children and adolescents aged from 4 to 17 underwent to clinical tests to demonstrate the oral conditions and immunological to identify the cytokine levels and the RSTBAs by colorimetry trial. There was a significant difference in saliva samples compared to that of peripheral blood in study cytokines and RSTBAs: IL-1 (blood: 1.646 ± 0.13 pg/mL, saliva: 552.36 ± 75.7 pg/mL; IL-6 (blood: 3.506 ± 1.85 pg/mL, saliva: 26.89 ± 9.97 pg/mL: TNF-a (blood: 12.91 ± 3.05 pg/mL, saliva: 43.56 ± 6.44 pg/mL, RSTBA (blood: 9.46 ± 3.26 nmol/mL, saliva: 1.26 ± 0.03 nmol/mL. There was not a statistically significant difference among blood and saliva samples for IL-1, IL-6 and RSTBA values. As regards TNF-a it was demonstrated a significant correlation, r s= 0.78. There was not evidence of cells positive to O2 in study samples. Results of correlation analysis obtained among the saliva and serum samples not offer evidences that saliva may be used as body fluid allows substituting the serum determination of IL-1, IL-6 and RSTBA. In the case of the TNF-a, there was a significant correlation, which could to propose the possible substitution of serum samples for the salivary ones.

Predicting Transport of 3,5,6-Trichloro-2-Pyridinol Into Saliva Using a Combination Experimental and Computational Approach.

Science.gov (United States)

Smith, Jordan Ned; Carver, Zana A; Weber, Thomas J; Timchalk, Charles

2017-06-01

A combination experimental and computational approach was developed to predict chemical transport into saliva. A serous-acinar chemical transport assay was established to measure chemical transport with nonphysiological (standard cell culture medium) and physiological (using surrogate plasma and saliva medium) conditions using 3,5,6-trichloro-2-pyridinol (TCPy) a metabolite of the pesticide chlorpyrifos. High levels of TCPy protein binding were observed in cell culture medium and rat plasma resulting in different TCPy transport behaviors in the 2 experimental conditions. In the nonphysiological transport experiment, TCPy reached equilibrium at equivalent concentrations in apical and basolateral chambers. At higher TCPy doses, increased unbound TCPy was observed, and TCPy concentrations in apical and basolateral chambers reached equilibrium faster than lower doses, suggesting only unbound TCPy is able to cross the cellular monolayer. In the physiological experiment, TCPy transport was slower than nonphysiological conditions, and equilibrium was achieved at different concentrations in apical and basolateral chambers at a comparable ratio (0.034) to what was previously measured in rats dosed with TCPy (saliva:blood ratio: 0.049). A cellular transport computational model was developed based on TCPy protein binding kinetics and simulated all transport experiments reasonably well using different permeability coefficients for the 2 experimental conditions (1.14 vs 0.4 cm/h for nonphysiological and physiological experiments, respectively). The computational model was integrated into a physiologically based pharmacokinetic model and accurately predicted TCPy concentrations in saliva of rats dosed with TCPy. Overall, this study demonstrates an approach to predict chemical transport in saliva, potentially increasing the utility of salivary biomonitoring in the future. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights

Selected antibacterial factors in the saliva of diabetic patients.

Science.gov (United States)

Malicka, Barbara; Kaczmarek, Urszula; Skośkiewicz-Malinowska, Katarzyna

2015-03-01

Diabetes mellitus leads to many systemic complications, including changes in the morphology, function of the salivary glands, and the composition of saliva. The study comprised a randomly selected 156 adults, of both genders, aged from 21 to 79, out of which patients with diabetes type 1 and 2, and healthy subjects forming two control age- and gender matched to the ill subjects. In unstimulated mixed saliva, total protein, peroxidase, myeloperoxidase and immunoglobulin A were measured as well as salivary flow rate. The periodontal condition was assessed with the use of GI, mSBI and PSR index. The obtained data were analysed with the use of U Mann-Whitney's test, Spearman's rang correlation and Chi-square test at a significant level of p diabetics in comparison to healthy age and gender matched control group had a lower salivary flow rate (p diabetics in comparison to control subjects had a higher level of total protein concentration (p diabetes type 1 and 2 can cause abnormalities in salivary glands function resulting in the diminishing of salivary flow rate and the increase in total protein content. Higher levels of myeloperoxidase and IgA in the saliva can be linked to worse periodontal condition in the diabetic patients. Copyright © 2014. Published by Elsevier Ltd.

Effectiveness of tramadol/paracetamol compared with etoricoxib as ...

African Journals Online (AJOL)

paracetamol combination when compared with etoricoxib as postoperative analgesia following day care surgery. Design: This was a prospective, randomised, single-blind study. Setting and subjects: Sixty-two patients were randomised to receive ...

Paracetamol, Ibuprofen, and Recurrent Major Cardiovascular and Major Bleeding Events in 19 120 Patients With Recent Ischemic Stroke.

Science.gov (United States)

Gonzalez-Valcarcel, Jaime; Sissani, Leila; Labreuche, Julien; Bousser, Marie-Germaine; Chamorro, Angel; Fisher, Marc; Ford, Ian; Fox, Kim M; Hennerici, Michael G; Mattle, Heinrich P; Rothwell, Peter M; Steg, Philippe Gabriel; Vicaut, Eric; Amarenco, Pierre

2016-04-01

The presumed safety of paracetamol in high-cardiovascular risk patients has been questioned. We determined whether paracetamol or ibuprofen use is associated with major cardiovascular events (MACE) or major bleeding in 19 120 patients with recent ischemic stroke or transient ischemic attack of mainly atherothrombotic origin included in the Prevention of cerebrovascular and cardiovascular events of ischemic origin with terutroban in patients with a history of ischemic stroke or transient ischemic attack (PERFORM) trial. We performed 2 nested case-control analysis (2153 cases with MACE during trial follow-up and 4306 controls matched on Essen stroke risk score; 809 cases with major bleeding matched with 1616 controls) and a separate time-varying analysis. 12.3% were prescribed paracetamol and 2.5% ibuprofen. Median duration of treatment was 14 (interquartile range 5-145) days for paracetamol and 9 (5-30) days for ibuprofen. Paracetamol, but not ibuprofen, was associated with increased risk of MACE (odds ratio 1.21, 95% confidence interval [CI] 1.04-1.42) or a major bleeding (odds ratio 1.60, 95% CI 1.26-2.03), with no impact of daily dose and duration of paracetamol treatment. Time-varying analysis found an increased risk of MACE with both paracetamol (hazard ratio 1.22, 95% CI 1.05-1.43) and ibuprofen (hazard ratio 1.47, 95% CI 1.06-2.03) and of major bleeding with paracetamol (hazard ratio 1.95, 95% CI 1.45-2.62). There was a weak and inconsistent signal for association between paracetamol or ibuprofen and MACE or major bleeding, which may be related to either a genuine but modest effect of these drugs or to residual confounding. http://www.isrctn.com. Unique identifier: ISRCTN66157730. © 2016 American Heart Association, Inc.

[Perianal and rectal ulcers due to abuse of paracetamol-codeine suppositories].

Science.gov (United States)

Wagner, G; Sand, C; Sachse, M M

2015-03-01

A 61-year-old woman presented with a progressive perianal ulcer which had developed 4 months ago. Upon further examination, another ulcer of the rectum was detected. Anorectal malignancies, viral infections or primary inflammatory bowel disease were not found. It could be demonstrated that the ulcers were induced by paracetamol and codeine suppositories. After discontinuation of these suppositories, the perianal ulcers healed almost completely within 3 weeks. The pathogenesis of paracetamol-induced ulcers is unknown. However, dose-dependent vasoconstriction is a possible explanation.

The proteome of human saliva

Science.gov (United States)

Griffin, Timothy J.

2013-05-01

Human saliva holds tremendous potential for transforming disease and health diagnostics given its richness of molecular information and non-invasive collection. Enumerating its molecular constituents is an important first step towards reaching this potential. Among the molecules in saliva, proteins and peptides arguably have the most value: they can directly indicate biochemical functions linked to a health condition/disease state, and they are attractive targets for biomarker assay development. However, cataloging and defining the human salivary proteome is challenging given the dynamic, chemically heterogeneous and complex nature of the system. In addition, the overall human saliva proteome is composed of several "sub-proteomes" which include: intact full length proteins, proteins carrying post-translational modifications (PTMs), low molecular weight peptides, and the metaproteome, derived from protein products from nonhuman organisms (e.g. microbes) present in the oral cavity. Presented here will be a summary of communal efforts to meet the challenge of characterizing the multifaceted saliva proteome, focusing on the use of mass spectrometry as the proteomic technology of choice. Implications of these efforts to characterize the salivary proteome in the context of disease diagnostics will also be discussed.

Synergistic interactions between paracetamol and oxcarbazepine in somatic and visceral pain models in rodents.

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Tomić, Maja A; Vucković, Sonja M; Stepanović-Petrović, Radica M; Ugresić, Nenad D; Prostran, Milica S; Bosković, Bogdan

2010-04-01

Combination therapy is a valid approach in pain treatment, in which a reduction of doses could reduce side effects and still achieve optimal analgesia. We examined the effects of coadministered paracetamol, a widely used non-opioid analgesic, and oxcarbazepine, a relatively novel anticonvulsant with analgesic properties, in a rat model of paw inflammatory hyperalgesia and in a mice model of visceral pain and determined the type of interaction between components. The effects of paracetamol, oxcarbazepine, and their combinations were examined in carrageenan-induced (0.1 mL, 1%) paw inflammatory hyperalgesia in rats and in an acetic acid-induced (10 mg/kg, 0.75%) writhing test in mice. In both models, drugs were coadministered in fixed-dose fractions of the 50% effective dose (ED(50)), and type of interaction was determined by isobolographic analysis. Paracetamol (50-200 mg/kg peroral), oxcarbazepine (40-160 mg/kg peroral), and their combination (1/8, 1/4, 1/3, and 1/2 of a single drug ED(50)) produced a significant, dose-dependent antihyperalgesia in carrageenan-injected rats. In the writhing test in mice, paracetamol (60-180 mg/kg peroral), oxcarbazepine (20-80 mg/kg peroral), and their combination (1/16, 1/8, 1/4, and 1/2 of a single drug ED(50)) significantly and dose dependently reduced the number of writhes. In both models, isobolographic analysis revealed a significant synergistic interaction between paracetamol and oxcarbazepine, with a >4-fold reduction of doses of both drugs in combination, compared with single drugs ED(50). The synergistic interaction between paracetamol and oxcarbazepine provides new information about combination pain treatment and should be explored further in patients, especially with somatic and/or visceral pain.

Neem gum as a binder in a formulated paracetamol tablet with reference to Acacia gum BP.

Science.gov (United States)

Ogunjimi, Abayomi Tolulope; Alebiowu, Gbenga

2014-04-01

This study determined the physical, compressional, and binding properties of neem gum (NMG) obtained from the trunk of Azadirachta indica (A Juss) in a paracetamol tablet formulation in comparison with official Acacia gum BP (ACA). The physical and flow properties were evaluated using density parameters: porosity, Carr's index, Hausner's ratio, and flow rate. Compressional properties were analyzed using Heckel and Kawakita equations. The tensile strength, brittle fracture index, and crushing strength-friability/disintegration time ratio were used to evaluate the mechanical properties of paracetamol tablets while the drug release properties of the tablets were assessed using disintegration time and dissolution times. Tablet formulations containing NMG exhibited faster onset and higher amount of plastic deformation during compression than those containing ACA. Neem gum produced paracetamol tablets with lower mechanical strength; however, the tendency of the tablets to cap or laminate was lower when compared to those containing ACA. Inclusion of NMG improved the balance between binding and disintegration properties of paracetamol tablets produced than those containing ACA. Neem gum produced paracetamol tablets with lower disintegration and dissolution times than those containing ACA.

Age-Related Changes in the Hepatic Pharmacology and Toxicology of Paracetamol

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Sarah J. Mitchell

2011-01-01

Full Text Available Optimal pharmacotherapy is determined when the pharmacokinetics and pharmacodynamics of the drug are understood. However, the age-related changes in pharmacokinetics and pharmacodynamics, as well as the increased interindividual variation mean optimal dose selection are a challenge for prescribing in older adults. Poor understanding of how hepatic clearance and toxicity are different with age results in suboptimal dose selection, poor efficacy, and/or increased toxicity. Of particular concern is the analgesic paracetamol which has been in use for more than 50 years and is consumed by a large proportion of older adults. Paracetamol is considered to be a relatively safe drug; however, caution must be taken because of its potential for toxicity. Paracetamol-induced liver injury from accidental overdose accounts for up to 55% of cases in older adults. Better understanding of how age affects the hepatic clearance and toxicity of drugs will contribute to evidence-based prescribing for older people, leading to fewer adverse drug reactions without loss of benefit.

Detection of Pseudomonas aeruginosa Metabolite Pyocyanin in Water and Saliva by Employing the SERS Technique

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Olga Žukovskaja

2017-07-01

Full Text Available Pyocyanin (PYO is a metabolite specific for Pseudomonas aeruginosa. In the case of immunocompromised patients, it is currently considered a biomarker for life-threating Pseudomonas infections. In the frame of this study it is shown, that PYO can be detected in aqueous solution by employing surface-enhanced Raman spectroscopy (SERS combined with a microfluidic platform. The achieved limit of detection is 0.5 μM. This is ~2 orders of magnitude below the concentration of PYO found in clinical samples. Furthermore, as proof of principle, the SERS detection of PYO in the saliva of three volunteers was also investigated. This body fluid can be collected in a non-invasive manner and is highly chemically complex, making the detection of the target molecule challenging. Nevertheless, PYO was successfully detected in two saliva samples down to 10 μM and in one sample at a concentration of 25 μM. This indicates that the molecules present in saliva do not inhibit the efficient adsorption of PYO on the surface of the employed SERS active substrates.

Is parotid saliva sterile on entry to the oral cavity?

DEFF Research Database (Denmark)

Schrøder, Stine A; Bardow, Allan; Eickhardt-Dalbøge, Steffen

2017-01-01

CONCLUSION: The present study indicates that parotid saliva is sterile on entry to the oral cavity. OBJECTIVES: The objective was to investigate if parotid saliva is sterile on entry to the oral cavity and, thus, prior to contamination by oral bacteria. METHOD: Forty healthy volunteers were...... included in sterile parotid saliva collection. Parotid saliva was collected using a sterile Lashley cup, placed over the papilla of the Stensen´s duct, as well as sterile tubes and syringes for collection. All collections were followed by collection of a positive control sample where some of the sterile...... obtained parotid saliva had been exposed to the contralateral mucosal membranes. All samples parotid saliva, as well as the positive controls, were cultivated, and 10 randomly selected parotid saliva samples underwent polymerase chain reaction (PCR) analyses. RESULTS: In 33 of 40 parotid saliva samples...

Efficacy of Paracetamol in Closure of Ductus Arteriosus in Infants under 32 Weeks of Gestation

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Ines Tofe

2018-02-01

Full Text Available BackgroundStandard medical treatment for patent ductus arteriosus (PDA closure has been indomethacin/ibuprofen or surgical ligation. Up to date, new strategies have been reported with paracetamol. The aim of this study was to present our experience with intravenous paracetamol for closing PDA in preterm neonates presenting contraindication to ibuprofen or ibuprofen had failed and no candidates for surgical ligation because of huge instability.Materials and methodsWe conducted a retrospective case series study in a neonatal intensive care unit from a tertiary hospital. 9 preterm infants ≤32 weeks of gestational age with hemodynamically significant PDA (hsPDA were enrolled. They received 15 mg/kg/6h intravenous paracetamol for ductal closure. Demographic data and transaminase levels before and after treatment were collected.Results30 preterm babies were diagnosed of hsPDA. 11/30 received ibuprofen with closure in 81.1%. 9 received intravenous paracetamol mainly due to bleeding disorders or thrombocytopenia. Successful closure on paracetamol was achieved in seven of nine babies (77.7%. There was a significant increase in transaminase levels in two patients. They required no treatment for normalization.ConclusionParacetamol is an effective option in closure PDA. It should be a first-line therapeutic option when there are contraindications for ibuprofen treatment. Transaminases must be checked during treatment.

Post-operative analgesic effects of paracetamol, NSAIDs, glucocorticoids, gabapentinoids and their combinations

DEFF Research Database (Denmark)

Dahl, Jørgen Berg; Nielsen, Rasmus; Wetterslev, Jørn

2014-01-01

, and no well-documented 'gold standards' exist. The aim of the present topical, narrative review is to provide an update of the evidence for post-operative analgesic efficacy with the most commonly used, systemic non-opioid drugs, paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs)/COX-2 antagonists......, glucocorticoids, gabapentinoids, and combinations of these. The review is based on data from previous systematic reviews with meta-analyses, investigating effects of non-opioid analgesics on pain, opioid-requirements, and opioid-related adverse effects. Paracetamol, NSAIDs, COX-2 antagonists, and gabapentin....... Trials of pregabalin > 300 mg/day indicated a morphine-sparing effect of 13.4 (4, 22.8) mg morphine/24 h. Notably, though, the available evidence for additive or synergistic effects of most combination regimens was sparse or lacking. Paracetamol, NSAIDs, selective COX-2 antagonists, and gabapentin all...

Estimating children's exposure to toxic elements in contaminated toys and children's jewelry via saliva mobilization.

Science.gov (United States)

Guney, Mert; Nguyen, Alain; Zagury, Gerald J

2014-09-19

Children's potential for exposure to potentially toxic elements in contaminated jewelry and toys via mouth contact has not yet been fully evaluated. Various toys and jewelry (metallic toys and jewelry [MJ], plastic toys, toys with paint or coating, and brittle/pliable toys; n = 32) were tested using the saliva extraction (mouthing) compartment of the DIN and RIVM bioaccessibility protocols to assess As, Ba, Cd, Cr, Cu, Mn, Ni, Pb, Sb, and Se mobilization via saliva. Total concentrations of As, Cd, Cu, Ni, Pb, and Sb were found elevated in analyzed samples. Four metals were mobilized to saliva from 16 MJ in significant quantities (>1 μg for highly toxic Cd and Pb, >10 μg for Cu and Ni). Bioaccessible concentrations and hazard index values for Cd exceeded limit values, for young children between 6 mo- and 3 yr-old and according to both protocols. Total and bioaccessible metal concentrations were different and not always correlated, encouraging the use of bioaccessibility for more accurate hazard assessments. Bioaccessibility increased with increasing extraction time. Overall, the risk from exposure to toxic elements via mouthing was high only for Cd and for MJ. Further research on children's exposure to toxic elements following ingestion of toy or jewelry material is recommended.

Comparison of oral paracetamol versus ibuprofen in premature infants with patent ductus arteriosus: a randomized controlled trial.

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Dan Dang

Full Text Available TRIAL DESIGN: Oral ibuprofen has demonstrated good effects on symptomatic patent ductus arteriosus (PDA but with many contraindications and potential side-effects. In the past two years, oral paracetamol administration to several preterm infants with PDA has been reported. Here, a randomized, non-blinded, parallel-controlled and non-inferiority trial was designed to evaluate the efficacy and safety profiles of oral paracetamol to those of standard ibuprofen for PDA closure in premature infants. METHODS: One hundred and sixty infants (gestational age ≤ 34 weeks with echocardiographically confirmed PDA were randomly assigned to receive either oral paracetamol (n = 80 or ibuprofen (n = 80. After the initial treatment course in both groups, the need for a second course was determined by echocardiographic evaluation. The main outcome was rate of ductal closure, and secondary outcomes were adverse effects and complications. RESULT: The ductus was closed in 65 (81.2% infants of the paracetamol group compared with 63 (78.8% of the ibuprofen group. The 95% confidence interval of the difference between these groups was [-0.080,0.128], demonstrating that the effectiveness of paracetamol treatment was not inferior to that of ibuprofen. In fact, the incidence of hyperbilirubinemia or gastrointestinal bleeding in the paracetamol group was significantly lower than that of the ibuprofen group. No significant differences in other clinical side effects or complications were noted. CONCLUSION: This comparison of drug efficacy and safety profiles in premature infants with PDA revealed that oral paracetamol was comparable to ibuprofen in terms of the rate of ductal closure and even showed a decreased risk of hyperbilirubinemia or gastrointestinal bleeding. Therefore, paracetamol may be accepted as a first-line drug treatment for PDA in preterm infants. TRIAL REGISTRATION: ChiCTR.org ChiCTR-TRC-12002177.

Overview review: Comparative efficacy of oral ibuprofen and paracetamol (acetaminophen) across acute and chronic pain conditions.

Science.gov (United States)

Moore, R A; Derry, S; Wiffen, P J; Straube, S; Aldington, D J

2015-10-01

Ibuprofen and paracetamol have long been used as analgesics in a range of acute, intermittent and chronic pain conditions. Paracetamol is often the first line analgesic recommended, without consensus about which is the better analgesic. An overview review of systematic reviews and meta-analyses directly compares ibuprofen and paracetamol at standard doses in particular painful conditions, or uses indirect comparisons against placebo. Electronic searches for systematic reviews were sought published since 1995 using outcomes approximating to ≥50% pain intensity reduction. Painful conditions were acute post-operative pain, dysmenorrhoea, tension-type headache (TTH), migraine, osteoarthritis and rheumatoid arthritis, back pain, cancer and paediatric pain. There was no systematic assessment of harm. Sixteen systematic reviews and four individual patient data meta-analyses were included. Ibuprofen was consistently superior to paracetamol at conventional doses in a range of painful conditions. Two direct comparisons favoured ibuprofen (acute pain, osteoarthritis). Three of four indirect comparisons favoured ibuprofen (acute pain, migraine, osteoarthritis); one showed no difference (TTH), although there were methodological problems. In five pain conditions (dysmenorrhoea, paediatric pain, cancer pain, back pain and rheumatoid arthritis), there were limited data on paracetamol and ibuprofen. At standard doses in different painful conditions, ibuprofen was usually superior producing more patients with the degree of pain relief that patients feel worthwhile. Neither of the drugs will be effective for everyone, and both are needed. This overview questions the practice of routinely using paracetamol as a first line analgesic because there is no good evidence for efficacy of paracetamol in many pain conditions. © 2014 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFICC®.

Some mechanisms involved in the radiosensitization of E. coli B/r by paracetamol

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Shenoy, M A; Gopalakrishna, K [Bhabha Atomic Research Centre, Bombay (India). Biology and Agriculture Div.

1977-06-01

Paracetamol, a widely-used analgesic and antipyretic drug, sensitized E.coli B/r to /sup 60/Co gamma rays under hypoxic conditions. Part of the sensitizing effect has been shown to be due to an electron adduct of the drug. Paracetamol inhibited both post-irradiation DNA and protein syntheses. The targets involved in the inhibition of post-irradiation DNA synthesis have been shown to be different in the presence of the sensitizer. Increased DNA degradation after irradiation was also observed when E.coli B/r were irradiated in the presence of the drug. The presence of paracetamol during hypoxic irradiation of E.coli B/r resulted in the enhancement of DNA single-strand scissions with no apparent effect on their rejoining.

Some mechanisms involved in the radiosensitization of E.coli B/r by paracetamol

International Nuclear Information System (INIS)

Shenoy, M.A.; Gopalakrishna, K.

1977-01-01

Paracetamol, a widely-used analgesic and antipyretic drug, sensitized E.coli B/r to 60 Co gamma-rays under hypoxic conditions. Part of the sensitizing effect has been shown to be due to an electron adduct of the drug. Paracetamol inhibited both post-irradiation DNA and protein syntheses. The targets involved in the inhibition of post-irradiation DNA synthesis have been shown to be different in the presence of the sensitizer. Increased DNA degradation after irradiation was also observed when E.coli B/r were irradiated in the presence of the drug. The presence of paracetamol during hypoxic irradiation of E.coli B/r resulted in the enhancement of DNA single-strand scissions with no apparent effect on their rejoining. (author)

Biomonitorization of cadmium, chromium, manganese, nickel and lead in whole blood, urine, axillary hair and saliva in an occupationally exposed population

Energy Technology Data Exchange (ETDEWEB)

Gil Fernando, E-mail: fgil@ugr.es [Department of Legal Medicine and Toxicology, University of Granada, School of Medicine (Spain); Hernandez, Antonio F. [Department of Legal Medicine and Toxicology, University of Granada, School of Medicine (Spain); Marquez, Claudia [Internal Resident in Occupational Medicine, School of Occupational Medicine of University of Granada (Spain); Femia, Pedro [Department of Statistics, University of Granada, School of Medicine (Spain); Olmedo, Pablo; Lopez-Guarnido, Olga; Pla, Antonio [Department of Legal Medicine and Toxicology, University of Granada, School of Medicine (Spain)

2011-02-15

Heavy metal contamination from occupational origin is a cause for concern because of its potential accumulation in the environment and in living organisms leading to long term toxic effects. This study was aimed to assess Cd, Cr, Mn, Ni and Pb levels in whole blood, urine, axillary hair and saliva from 178 individuals with occupational exposure to heavy metals. Levels of metal compounds were determined by atomic absorption spectrometry. We collected information on occupation, lifestyle habits and food intake by questionnaire. Multiple linear regression analyses for metal ion concentration in whole blood, urine, axillary hair and saliva were adjusted for age, gender, smoking and alcohol consumption, lifetime workplace exposure, residence area and food habits. Overall, blood and urine median concentrations found for the five metals analyzed do not exceed biological exposure indexes, so that they are very similar to a non-occupationally exposed population. Toxicokinetic differences may account for the lack of correlations found for metal levels in hair and saliva with those in blood or urine. For those heavy metals showing higher median levels in blood with respect to hair (Cd, Mn and Pb) indicating lesser hair incorporation from blood, the lifetime working experience was inversely correlated with their hair levels. The longer the lifetime working experience in industrial environments, the higher the Mn and Ni concentration in saliva. Axillary hair and saliva may be used as additional and/or alternative samples to blood or urine for biomonitoring hair Mn, and saliva Ni in subjects with occupational exposure. - Research Highlights: {yields} Metal levels in workers were similar to an occupationally non-exposed population. {yields} Metal levels in blood and urine were below recommended reference values. {yields} A lack of correlation was observed between metal levels in blood and saliva. {yields} Toxicokinetic differences may account for the lack of correlations observed

Radioimmunological analysis of circadian rhythms of cortisol and melatonin in saliva

International Nuclear Information System (INIS)

Demel, A.W.

1990-12-01

Since blood cortisol (F) and melatonin (MTL) display a circadian secretion pattern and since the saliva concentration of these hormones is an excellent indicator of its blood levels the measurement of salivary F and MLT may be used for examining circadian rhythmicity. In these study the relationship between salivary F and MLT was explored. For this purpose it was necessary first to establish and validate a radioimmunoassay for F in saliva: salivary F was determined by a direct radioimmunoassay using cortisol-3-(O-carboxymethyl) oximino-(2- ( 125 I)iodohistamin) as tracer and cortisol-3-CMO-BSA antiserum. The parallel measurement of F levels in saliva and serum of adults gave an excellent correlation (r=0.87, p 0.00956x ). Serum F was assayed on the Abott TDX-System using a radioimmunofluorescence method. Secondly, using this assay the circadian saliva F pattern was determined as well as the pattern of salivary MLT in 9 young, healthy volunteers. For saliva MLT estimations a previously published method was applied (SCHULZ et al 1990). Using a computerized program (RHYTHM) written by EVE v. CAUTER (1979), the hormone data of each individuum were examined for circadian rhythmicity and its acrophases (time of occurrence of the maximum of a sinusoid fitted to the data). The F acrophase occured between 7:00 and 12:00 h (Mean: 8:06 h, SD: 93.8 min). The acrophase for MLT was found between 0:00 and 6:00 h (Mean: 3:33 h, SD: 104.4 min). There was a phase difference between both hormones of 3 to 7 hours (Mean: 292.5 min, SD: 74.7 min). The easy stress-free non-invasive nature of saliva collection makes saliva to one of the most accessible body fluids and of high value in studying the circadian system in healthy humans as well as in infants, children, pregnant women and anaemic patients. Measurements of salivary F and MLT may help to elucidate not only the circadian rhythms of these hormones under normal and pathological conditions but it may also provide insight in

Improving ambulatory saliva-sampling compliance in pregnant women: a randomized controlled study.

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Julian Moeller

Full Text Available OBJECTIVE: Noncompliance with scheduled ambulatory saliva sampling is common and has been associated with biased cortisol estimates in nonpregnant subjects. This study is the first to investigate in pregnant women strategies to improve ambulatory saliva-sampling compliance, and the association between sampling noncompliance and saliva cortisol estimates. METHODS: We instructed 64 pregnant women to collect eight scheduled saliva samples on two consecutive days each. Objective compliance with scheduled sampling times was assessed with a Medication Event Monitoring System and self-reported compliance with a paper-and-pencil diary. In a randomized controlled study, we estimated whether a disclosure intervention (informing women about objective compliance monitoring and a reminder intervention (use of acoustical reminders improved compliance. A mixed model analysis was used to estimate associations between women's objective compliance and their diurnal cortisol profiles, and between deviation from scheduled sampling and the cortisol concentration measured in the related sample. RESULTS: Self-reported compliance with a saliva-sampling protocol was 91%, and objective compliance was 70%. The disclosure intervention was associated with improved objective compliance (informed: 81%, noninformed: 60%, F(1,60  = 17.64, p<0.001, but not the reminder intervention (reminders: 68%, without reminders: 72%, F(1,60 = 0.78, p = 0.379. Furthermore, a woman's increased objective compliance was associated with a higher diurnal cortisol profile, F(2,64  = 8.22, p<0.001. Altered cortisol levels were observed in less objective compliant samples, F(1,705  = 7.38, p = 0.007, with delayed sampling associated with lower cortisol levels. CONCLUSIONS: The results suggest that in pregnant women, objective noncompliance with scheduled ambulatory saliva sampling is common and is associated with biased cortisol estimates. To improve sampling compliance, results suggest

Acute liver failure in a term neonate after repeated paracetamol administration

OpenAIRE

Bucaretchi, Fabio; Fernandes, Carla Borrasca; Branco, Maira Migliari; Capitani, Eduardo Mello De; Hyslop, Stephen; Caldas, Jamil Pedro S.; Moreno, Carolina Araujo; Porta, Gilda

2014-01-01

Objective: Severe hepatotoxicity caused by paracetamol is rare in neonates. We report a case of paracetamol-induced acute liver failure in a term neonate. Case description: A 26-day-old boy was admitted with intestinal bleeding, shock signs, slight liver enlargement, coagulopathy, metabolic acidosis (pH=7.21; bicarbonate: 7.1mEq/L), hypoglycemia (18mg/dL), increased serum aminotransferase activity (AST=4,039IU/L; ALT=1,087IU/L) and hyperbilirubinemia (total: 9.57mg/dL; direct: 6.18mg/dL)...

Adverse effects of perioperative paracetamol, NSAIDs, glucocorticoids, gabapentinoids and their combinations

DEFF Research Database (Denmark)

Mathiesen, O; Wetterslev, Jørn; Kontinen, V K

2014-01-01

with the most common perioperative non-opioid analgesics: paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids (GCCs), gabapentinoids and their combinations. The review is based on data from systematic reviews with meta-analyses of analgesic efficacy and/or adverse effects...... of perioperative non-opioid analgesics, and randomised trials and cohort/retrospective studies. Generally, data on AE are sparse and related to the immediate post-operative period. For paracetamol, the incidence of AEs appears trivial. Data are inconclusive regarding an association of NSAIDs with mortality...

Changes in the pattern of paracetamol use in the periconception period in a Danish cohort

DEFF Research Database (Denmark)

Ersbøll, Anne S; Hedegaard, Mette; Damm, Peter

2015-01-01

Paracetamol is the most commonly used over-the-counter drug in pregnancy. It is generally considered to be safe, but prolonged antenatal exposure has been associated with offspring short- and long-term morbidity. Our aim was to describe the pattern of paracetamol use with a focus on frequent...... ingestion (more than once a week), 3 months before and in early pregnancy. In this cohort, 8650 pregnant women responded to a web-based clinical questionnaire that included questions about drug use. Paracetamol was the most used drug before and in early pregnancy (35.2% and 6.5% of respondents, respectively......). The proportion of frequent users decreased from 3.9% before to 0.9% in early pregnancy. Frequent paracetamol use was associated with smoking, co-morbidities, body mass index ≥ 25 kg/m(2), unplanned pregnancy, no education and inability to understand Danish. A significant decrease in the proportion of women...

Paracetamol in Patent Ductus Arteriosus Treatment: Efficacious and Safe?

Science.gov (United States)

Bardanzellu, Flaminia; Neroni, Paola; Fanos, Vassilios

2017-01-01

In preterm infants, failure or delay in spontaneous closure of Ductus Arteriosus (DA), resulting in the condition of Patent Ductus Arteriosus (PDA), represents a significant issue. A prolonged situation of PDA can be associated with several short- and long-term complications. Despite years of researches and clinical experience on PDA management, unresolved questions about the treatment and heterogeneity of clinical practices in different centers still remain, in particular regarding timing and modality of intervention. Nowadays, the most reasonable strategy seems to be reserving the treatment only to hemodynamically significant PDA. The first-line therapy is medical, and ibuprofen, related to several side effects especially in terms of nephrotoxicity, is the drug of choice. Administration of oral or intravenous paracetamol (acetaminophen) recently gained attention, appearing effective as traditional nonsteroidal anti-inflammatory drugs (NSAIDs) in PDA closure, with lower toxicity. The results of the studies analyzed in this review mostly support paracetamol efficacy in ductal closure, with inconstant low and transient elevation of liver enzymes as reported side effect. However, more studies are needed to confirm if this therapy shows a real safety profile and to evaluate its long-term outcomes, before considering paracetamol as first-choice drug in PDA treatment. PMID:28828381

Paracetamol in Patent Ductus Arteriosus Treatment: Efficacious and Safe?

Directory of Open Access Journals (Sweden)

Flaminia Bardanzellu

2017-01-01

Full Text Available In preterm infants, failure or delay in spontaneous closure of Ductus Arteriosus (DA, resulting in the condition of Patent Ductus Arteriosus (PDA, represents a significant issue. A prolonged situation of PDA can be associated with several short- and long-term complications. Despite years of researches and clinical experience on PDA management, unresolved questions about the treatment and heterogeneity of clinical practices in different centers still remain, in particular regarding timing and modality of intervention. Nowadays, the most reasonable strategy seems to be reserving the treatment only to hemodynamically significant PDA. The first-line therapy is medical, and ibuprofen, related to several side effects especially in terms of nephrotoxicity, is the drug of choice. Administration of oral or intravenous paracetamol (acetaminophen recently gained attention, appearing effective as traditional nonsteroidal anti-inflammatory drugs (NSAIDs in PDA closure, with lower toxicity. The results of the studies analyzed in this review mostly support paracetamol efficacy in ductal closure, with inconstant low and transient elevation of liver enzymes as reported side effect. However, more studies are needed to confirm if this therapy shows a real safety profile and to evaluate its long-term outcomes, before considering paracetamol as first-choice drug in PDA treatment.

Saliva as a diagnostic fluid: literature review

OpenAIRE

Martí Álamo, Silvia; Mancheño Franch, Aisha; Marzal Gamarra, Cristina

2012-01-01

There is a growing interest in diagnosis based on the analysis of saliva. This is a simple, non-invasive method of obtaining oral samples which is safe for both the health worker and the patient, not to mention allowing for simple and cost-efficient storage. The majority of studies use general saliva samples in their entirety, complex fluids containing both local and systemic sources and whose composition corresponds to that of the blood. General saliva contains a considerable ...

Paracetamol (acetaminophen) or non-steroidal anti-inflammatory drugs, alone or combined, for pain relief in acute otitis media in children.

Science.gov (United States)

Sjoukes, Alies; Venekamp, Roderick P; van de Pol, Alma C; Hay, Alastair D; Little, Paul; Schilder, Anne Gm; Damoiseaux, Roger Amj

2016-12-15

Acute otitis media (AOM) is one of the most common childhood infectious diseases and a significant reason for antibiotic prescriptions in children worldwide. Pain from middle ear infection and pressure behind the eardrum is the key symptom of AOM. Ear pain is central to children's and parents' experience of the illness. Because antibiotics provide only marginal benefits, analgesic treatment including paracetamol (acetaminophen) and non-steroidal anti-inflammatory drugs (NSAIDs) is regarded as the cornerstone of AOM management in children. Our primary objective was to assess the effectiveness of paracetamol (acetaminophen) or NSAIDs, alone or combined, compared with placebo or no treatment in relieving pain in children with AOM. Our secondary objective was to assess the effectiveness of NSAIDs compared with paracetamol in children with AOM. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Issue 7, July 2016; MEDLINE (Ovid, from 1946 to August 2016), Embase (from 1947 to August 2016), CINAHL (from 1981 to August 2016), LILACS (from 1982 to August 2016) and Web of Science (from 1955 to August 2016) for published trials. We screened reference lists of included studies and relevant systematic reviews for additional trials. We searched WHO ICTRP, ClinicalTrials.gov, and the Netherlands Trial Registry (NTR) for completed and ongoing trials (search date 19 August 2016). We included randomised controlled trials (RCTs) comparing the effectiveness of paracetamol or NSAIDs, alone or combined, for pain relief in children with AOM. We also included trials of paracetamol or NSAIDs, alone or combined, for children with fever or upper respiratory tract infections (URTIs) if we were able to extract subgroup data on pain relief in children with AOM either directly or after obtaining additional data from study authors. Two review authors independently assessed methodological quality of the included trials and extracted data. We used the GRADE approach to rate

Het gebruik van paracetamol bij patiënten met levercirrose en het risico op hepatotoxiciteit

NARCIS (Netherlands)

Weersink, R.A.; Borgsteede, S.D.; Okel, E.; Pras, N.; Van Putten, A.W.

2016-01-01

OBJECTIVE: To study the safety and the optimal dose of paracetamol as an analgesic in patients with liver cirrhosis. DESIGN AND METHODS: In a literature search all pharmacokinetic and clinical studies concerning paracetamol use in patients with liver cirrhosis were retrieved, as well as review

The Paracetamol (Acetaminophen) In Stroke (PAIS) trial : a multicentre, randomised, placebo-controlled, phase III trial

NARCIS (Netherlands)

den Hertog, Heleen M.; van der Worp, H. Bart; van Gemert, H. Maarten A.; Algra, Ate; Kappelle, L. Jaap; Van Gijn, Jan; Koudstaal, Peter J.; Dippel, Diederik W. J.

Background High body temperature in the first 12-24 h after stroke onset is associated with poor functional outcome. The Paracetamol (Acetaminophen) In Stroke (PAIS) trial aimed to assess whether early treatment with paracetamol improves functional outcome in patients with acute stroke by reducing

Pharmacokinetics in Morbid Obesity: Influence of Two Bariatric Surgery Techniques on Paracetamol and Caffeine Metabolism.

Science.gov (United States)

Goday Arno, Albert; Farré, Magí; Rodríguez-Morató, Jose; Ramon, Jose M; Pérez-Mañá, Clara; Papaseit, Esther; Civit, Ester; Langohr, Klaus; Lí Carbó, Marcel; Boix, David Benaiges; Nino, Olga Castañer; Le Roux, Juana Antonia Flores; Pera, Manuel; Grande, Luis; de la Torre, Rafael

2017-12-01

The purpose of the study was to study the impact of the two most common bariatric surgery techniques on paracetamol pharmacokinetics (a marker of gastric emptying) and caffeine metabolism (a marker of liver function). In the present prospective study, we studied 24 morbid obese patients before, at 4 weeks, and 6 months after having undergone sleeve gastrectomy (n = 10) or Roux-en-Y gastric bypass (n = 14). For comparative purposes, 28 healthy controls (14 normal weights and 14 overweights) were also included in the study. Paracetamol pharmacokinetics was altered in the obese participants leading to lower bioavailability. Bariatric surgery resulted in faster absorption and normalized pharmacokinetic parameters, prompting an increase in paracetamol bioavailability. No differences were found between surgical procedures. In the case of caffeine, the ratio paraxanthine/caffeine did not differ between morbid obese and healthy individuals. This ratio remained unmodified after surgery, indicating that the liver function (assessed by cytochrome P450 1A2 activity) was unaffected by obesity or bariatric surgery. Paracetamol pharmacokinetics and caffeine plasma levels are altered in severely obese patients. The two studied bariatric surgical techniques normalize paracetamol oral bioavailability without impairing the liver function (measured by cytochrome P450 1A2 activity).

The haemodynamic effects of intravenous paracetamol (acetaminophen) in healthy volunteers: a double-blind, randomized, triple crossover trial.

Science.gov (United States)

Chiam, Elizabeth; Weinberg, Laurence; Bailey, Michael; McNicol, Larry; Bellomo, Rinaldo

2016-04-01

The haemodynamic effects of intravenous paracetamol have not been systematically investigated. We compared the physiological effects of intravenous mannitol-containing paracetamol, and an equivalent dosage of mannitol, and normal saline 0.9% in healthy volunteers. We performed a blinded, triple crossover, randomized trial of 24 adult healthy volunteers. Participants received i.v. paracetamol (1 g paracetamol +3.91 g mannitol 100 ml(-1) ), i.v. mannitol (3.91 g mannitol 100 ml(-1) ) and i.v. normal saline (100 ml). Composite primary end points were changes in mean arterial pressure (MAP), systolic blood pressure (SBP) and diastolic blood pressure (DBP) measured pre-infusion, during a 15 min infusion period and over a 45 min observation period. Systemic vascular resistance index (SVRI) and cardiac index were measured at the same time points. Infusion of paracetamol induced a transient yet significant decrease in blood pressures from pre-infusion values (MAP -1.85 mmHg, 95% CI -2.6, -1.1, SBP -0.54 mmHg, 95% CI -1.7, 0.6 and DBP -1.92 mmHg, 95% CI -2.6, -1.2, P paracetamol caused a transient decrease in blood pressure immediately after infusion. These effects were not seen with mannitol or normal saline. The physiological mechanism was consistent with vasodilatation. This study provides plausible physiological data in a healthy volunteer setting, supporting transient changes in haemodynamic variables with i.v. paracetamol and justifies controlled studies in the peri-operative and critical care setting. © 2015 The British Pharmacological Society.

Comparative in-vitro analysis of different brands of paracetamol tablets available in Nepal

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Ganesh Man Singh Thakuri

2016-08-01

Full Text Available Objective: To examine the physico-chemical parameters of commercially available local and multinational brands of paracetamol tablets in Nepal. Methods: Different five paracetamol brands were explored by testing various parameters according to standard methods. The studied parameters included weight variation, friability, disintegration, dissolution and assay. The limits of the official test were referenced from official guidelines of Indian Pharmacopoeia (IP and British Pharmacopoeia (BP. All brands were tested according to their pharmacopoeial claim and methods for these tests were successfully conducted to find out their qualities. Those methods were economic and authentic. Results: Requirements of weight variation and friability value were complied by all brands. Fifteen minutes of disintegration time were also complied by all the brands according to the BP/IP recommendation for uncoated tablets. All brands showed not less than 80% drug release in 45 min as per BP and not less than 85% in 30 min as per IP. Content of each brand was found to be within the range of 95%–105%. The present findings suggested that about every paracetamol brand which was accessible in Nepali market encountering the IP/BP requirements. Conclusions: Although the physico-chemical examinations such as weight variation, friability, disintegration, dissolution and assay were detected varying brand wise, but were found interior to defined limits. Being an over-the-counter drug, the consumption of paracetamol is too high. Therefore, it is important for each brand to be genuine, good manufactured and well marketed. So, additional exploration over the quality of paracetamol is compulsory for safe human consumption.

Effects of glycemic control on saliva flow rates and protein composition in non-insulin-dependent diabetes mellitus.

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Dodds, M W; Dodds, A P

1997-04-01

The objective of this study was to determine whether improvements in the level of diabetic control in a group of subjects with poorly controlled non-insulin-dependent diabetes mellitus influence salivary output and composition. Repeated whole unstimulated and stimulated parotid saliva samples were collected from diabetic patients attending an outpatient diabetes education program and a matched nondiabetic control group. Saliva was analyzed for flow rates, parotid protein concentration and composition, and amylase activity. Subjective responses to questions about salivary hypofunction were tested. There were no significant differences in whole unstimulated and stimulated parotid flow rates or stimulated parotid protein concentration and composition between diabetics and the control group. Amylase activity was higher in diabetics and decreased with improved glycemic control. Subjects reporting taste alterations had higher mean blood glucose levels than subjects with normal taste sensation. Poorly controlled non-insulin-dependent diabetes mellitus has no influence on saliva output, although amylase activity may be elevated, and there may be taste alterations.

How well are national guidelines relating to the general sales of aspirin and paracetamol, adhered to by retail stores: a mystery shopper study

Science.gov (United States)

Molloy, Phillip; Chambers, Ruth; Cork, Tania

2016-01-01

Objective To determine whether non-pharmaceutical retail outlets are aboding to the current Medicines and Healthcare products Regulatory Agency (MHRA) national guidelines for over-the-counter (OTC) sales of aspirin and paracetamol. Methods Stages 1 and 2 of the study deployed eight and four medical students, respectively, to undertake a mystery shopper style investigation. Stage 1: eight medical students attempted to buy ≥96 tablets/capsules aspirin or paracetamol in one transaction in 62 shops. Stage 2: four medical students attempted to purchase 32 paracetamol 500 mg along with a ‘flu remedy preparation also containing paracetamol, in 54 shops. Results Stage 1 data revealed that 58% and 57% retailers sold more than the MHRA guidelines recommended for paracetamol and aspirin, respectively. We observed that 23% and 28% retailers were willing to sell ≥96 tablets of paracetamol or aspirin with no questions asked. Stage 2 results showed that 57% retailers sold 32×500 mg paracetamol in conjunction with a paracetamol-containing ‘flu preparation; while 98% shops sold 16×paracetamol 500 mg along with a paracetamol-containing ‘flu remedy, with no questions asked of the shopper or advice given. Discussion MHRA national guidelines for OTC medicines sales appear to be poorly adhered to in non-pharmacy shops. Sales of aspirin and paracetamol OTC must be better regulated in the UK to ultimately reduce morbidity and mortality rates of deliberate and accidental overdoses. PMID:26781508

Efek Pengunyahan Permen Karet Gula dan Xylitol terhadap Status Saliva

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Lisna Kurnia Rezky

2016-11-01

Full Text Available Latar belakang. Rongga mulut sebagai pintu masuk makanan ke dalam tubuh selalu dibasahi oleh saliva setiap harinya. Saat ini banyak produk permen karet yang beredar di masyarakat yang mengandung gula dan xylitol. Banyak orang yang gemar mengunyah permen karet dengan kurang memperhatikan komposisinya baik yang mengandung gula ataupun xylitol sehingga kurang mengetahui efek masing-masing jenis permen karet tersebut terhadap kesehatan rongga mulut. Tujuan. Penelitian ini bertujuan untuk mengetahui efek pengunyahan permen karet gula dengan permen karet xylitol terhadap status saliva yang terdiri dari volume, pH, dan viskositas saliva. Metode penelitian. Subjek penelitian berjumlah 30 orang dibagi menjadi 3 kelompok masing-masing 10 orang, terdiri dari kelompok mengunyah permen karet gula, xylitol, dan kontrol dengan mengunyah apel. Pengambilan saliva dilakukan pagi hari dan siang hari. Subjek mengunyah 2 butir permen karet dan tidak diperbolehkan untuk makan dan minum 1 jam sebelum mengunyah. Subjek diinstruksikan meludah ke dalam pot saliva selama 10 menit dalam interval setiap 1 menit. Pengukuran volume saliva menggunakan pipet volume, pH saliva dengan menggunakan pH meter, dan viskositas saliva dengan menggunakan viskometer Ostwald hari ke-1 dan ke-4. Analisis data dengan uji statistik Mann-Whitney. Hasil. penelitian menunjukkan adanya peningkatan bermakna volume dan viskositas saliva pada pengunyahan permen karet xylitol dan gula. Derajat keasaman (pH saliva menurun setelah mengunyah permen karet gula sedangkan pada perm en karet xylitol relatif stabil. Disimpulkan bahwa permen karet xylitollebih baik untuk kestabilan status saliva dibandingkan permen karet gula.

Fatal cerebral blødning på grund af mulig interaktionmellem paracetamol og warfarin

DEFF Research Database (Denmark)

Vinsand Naver, Signe; Papina, Maria; Jimenez Solem, Espen

2015-01-01

This is a case report of an 83-year-old man in warfarin treatment with stable international normalised ratio (INR) after aortic valve replacement and atrial fibrillation. Due to back pain he took paracetamol (acetaminophen) 4 g/day, morphine 30 mg/day and diclofenac as rescue medication for two...... paracetamol and warfarin are discussed....

Glucose-6-phosphate dehydrogenase deficiency: an unusual cause of acute jaundice after paracetamol overdose.

Science.gov (United States)

Phillpotts, Simon; Tash, Elliot; Sen, Sambit

2014-11-01

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the commonest human enzyme defect causing haemolytic anaemia after exposure to specific triggers. Paracetamol-induced haemolysis in G6PD deficiency is a rare complication and mostly reported in children. We report the first case (to the best of our knowledge) of acute jaundice without overt clinical features of a haemolytic crisis, in an otherwise healthy adult female following paracetamol overdose, due to previously undiagnosed G6PD deficiency. It is important that clinicians consider this condition when a patient presents following a paracetamol overdose with significant and disproportionate jaundice, without transaminitis or coagulopathy. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Intravenous paracetamol and patent ductus arteriosus closure in preterm infants

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Rizky Adriansyah

2017-08-01

Full Text Available Background Indomethacin and ibuprofen are the drugs of choice for closure of patent ductus arteriosus (PDA in preterm infants. However, intravenous preparations are of limited availability in Indonesia. Circumstantial evidence has shown that intravenous paracetamol may be an alternative therapy for PDA closure in premature infants. Objective To evaluate the effect of intravenous paracetamol on PDA closure in preterm infants. Methods A before-and-after study was conducted between May and August 2014 in Cipto Mangunkusumo General Hospital, Jakarta in preterm infants with hemodynamically significant PDAs, as established by echocardiography using the following criteria: duct diameter >1.4 mm/kg, left atrium to aorta ratio >1.4, and mean velocity in the left pulmonary artery >0.42 m/s or mean diastolic velocity in the left pulmonary artery >0.2 m/s. Subjects, aged 2 and 7 days, received intravenous paracetamol (15 mg/kg every six hours for 3 days. Paired T-test was used to compare pre-intervention PDA diameter to those assessed at 24 hours after the intervention and at 14 days of life. Results Twenty-nine subjects had a mean gestational age of 30.8 weeks and mean birth weight of 1,347 grams. Nineteen (65.5% patients had closed PDAs at the day 14 evaluation, 1 experienced PDA reopening, and 9 had failed PDA closure. No liver toxicity was identified. Mean duct diameters before, 24 hours after the intervention, and at 14 days of life were 3.0, 0.9, and 0.6 mm, respectively (P<0.0001. Conclusion Intravenous paracetamol seems to be reasonably effective for PDA closure in preterm infants.

[Risk of acute hepatic insufficiency in children due to chronic accidental overdose of paracetamol (acetaminophen)

NARCIS (Netherlands)

Hameleers-Snijders, P.; Hogeveen, M.; Smeitink, J.A.M.; Kramers, C.; Draaisma, J.M.T.

2007-01-01

Two girls aged 4 and 3 years, respectively, experienced acute liver failure due to accidental ingestion of supratherapeutic doses of paracetamol (90 mg/kg/day or more). Recognition of chronic paracetamol intoxication as a cause of acute hepatic failure is often delayed. It is important to consider

Ibuprofen and/or paracetamol (acetaminophen) for pain relief after surgical removal of lower wisdom teeth

NARCIS (Netherlands)

Bailey, E.; Worthington, H.V.; van Wijk, A.; Yates, J.M.; Coulthard, P.; Afzal, Z.

2013-01-01

Background Both paracetamol and ibuprofen are commonly used analgesics for the relief of pain following the surgical removal of lower wisdom teeth (third molars). In 2010, a novel analgesic (marketed as Nuromol) containing both paracetamol and ibuprofen in the same tablet was launched in the United

Disposable Collection Kit for Rapid and Reliable Collection of Saliva

OpenAIRE

Yamaguchi, Masaki; Tezuka, Yuki; Takeda, Kazunori; Shetty, Vivek

2015-01-01

Objectives To describe and evaluate disposable saliva collection kit for rapid, reliable, and reproducible collection of saliva samples. Methods The saliva collection kit comprised of a saliva absorbent swab and an extractor unit was used to retrieve whole saliva samples from 10 subjects. The accuracy and precision of the extracted volumes (3, 10, and 30 ?l) were compared to similar volumes drawn from control samples obtained by passive drool. Additionally, the impact of kit collection method...

N-Acetyl Cysteine does not prevent liver toxicity from chronic low dose plus sub-acute high dose paracetamol exposure in young or old mice

Science.gov (United States)

Kane, Alice-Elizabeth; Huizer-Pajkos, Aniko; Mach, John; McKenzie, Catriona; Mitchell, Sarah-Jayne; de Cabo, Rafael; Jones, Brett; Cogger, Victoria; Le Couteur, David G; Hilmer, Sarah-Nicole

2016-01-01

Paracetamol is an analgesic commonly used by people of all ages, which is well documented to cause severe hepatotoxicity with acute over-exposures. The risk of hepatotoxicity from non-acute paracetamol exposures is less extensively studied, and this is the exposure most common in older adults. Evidence on the effectiveness of N-acetyl cysteine (NAC) for non-acute paracetamol exposures, in any age group, is lacking. This study aimed to examine the effect of long-term exposure to therapeutic doses of paracetamol and sub-acute paracetamol over-exposure, in young and old mice, and to investigate whether NAC was effective at preventing paracetamol hepatotoxicity induced by these exposures. Young and old male C57BL/6 mice were fed a paracetamol-containing (1.33g/kg food) or control diet for 6 weeks. Mice were then dosed orally 8 times over 3 days with additional paracetamol (250mg/kg) or saline, followed by either one or two doses of oral NAC (1200mg/kg) or saline. Chronic low-dose paracetamol exposure did not cause hepatotoxicity in young or old mice, measured by serum alanine aminotransferase (ALT) elevation, and confirmed by histology and a DNA fragmentation assay. Sub-acute paracetamol exposure caused significant hepatotoxicity in young and old mice, measured by biochemistry (ALT) and histology. Neither a single nor double dose of NAC protected against this toxicity from sub-acute paracetamol in young or old mice. This finding has important clinical implications for treating toxicity due to different paracetamol exposure types in patients of all ages, and implies a need to develop new treatments for sub-acute paracetamol toxicity. PMID:26821200

A comparative study of ibuprofen with paracetamol versus oxyphenbutazone with analgin combination in ophthalmic practice

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Roy I

1988-01-01

Full Text Available A total of 200 patients of either sex with various ophthalmic inflammatory disorders of surgical and non-surgical types were treated with ibuprofen with paracetamol 1 tablet tid. or a combination of oxyphenbutazone and analgin-1 tablet t. i. d. for 7 days/ Patients in the ibuprofen with Paracetamol group recorded a signifi-cantly greater reduction in pain scores; on day 1 and 2 and in swelling scores on day 2, 5 and 7 as compared to patients receiving the combination of ox yphenbutazone and analgin. A significantly lesserr number of patients in the ibuprofen with paraeetamol group required escape analgesics. Seventy six per cent of patients in the Ibuprofen with paracetamol group were judged as showing a Very good - Good, response to treatment as against 55 per cent in the oxvphenbutazone-analgin group. It is concluded that ibuprofen with Paracetamol is superior in efficacy and a safer alternative to a combination of oxyphenbutazone and analgin.

Stability-Indicating RP-HPLC Method for Analysis of Paracetamol and Tramadol in a Pharmaceutical Dosage Form

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Rajesh M. Kamble

2012-01-01

Full Text Available A simple, isocratic, rapid and accurate reversed phase high performance liquid chromatography method was developed for the quantitative determination of paracetamol and tramadol in commercial medicinal tablets. The chromatographic separation was achieved on an Intersil C18 (250 mm x 4.6 mm, 5μm column using water pH 3.4 with orthophosphoric acid: methanol (60:40, v/v as a mobile phase, and UV detection at 228 nm. The chromatographic resolutions between paracetamol and tramadol were found greater than five. The linear range for paracetamol and tramadol were 20.8–39.0 μg/ml and 2.4–4.5 μg/ ml was obtained with correlation coefficients ≥0.999 for each analyte. The retention time were found to be 2.1 and 3.9 min for tramadol and paracetamol respectively. Paracetamol and tramadol was subjected to stress conditions (hydrolysis (acid, base oxidation, photolysis and thermal degradation and the stressed samples were analyzed by use of the method. The major degradation was observed in acid and minor in base, thermal, oxidation and photolysis. The forced degradation studies prove the stability indicating power of the method.

Biosensor-based real-time monitoring of paracetamol photocatalytic degradation.

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Calas-Blanchard, Carole; Istamboulié, Georges; Bontoux, Margot; Plantard, Gaël; Goetz, Vincent; Noguer, Thierry

2015-07-01

This paper presents for the first time the integration of a biosensor for the on-line, real-time monitoring of a photocatalytic degradation process. Paracetamol was used as a model molecule due to its wide use and occurrence in environmental waters. The biosensor was developed based on tyrosinase immobilization in a polyvinylalcohol photocrosslinkable polymer. It was inserted in a computer-controlled flow system installed besides a photocatalytic reactor including titanium dioxide (TiO2) as photocatalyst. It was shown that the biosensor was able to accurately monitor the paracetamol degradation with time. Compared with conventional HPLC analysis, the described device provides a real-time information on the reaction advancement, allowing a better control of the photodegradation process. Copyright © 2015 Elsevier Ltd. All rights reserved.

Simultaneous determination of eperisone hydrochloride and paracetamol in mouse plasma by high performance liquid chromatography-photodiode array detector.

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Locatelli, Marcello; Cifelli, Roberta; Di Legge, Cristina; Barbacane, Renato Carmine; Costa, Nicola; Fresta, Massimo; Celia, Christian; Capolupo, Carlo; Di Marzio, Luisa

2015-04-03

This paper reports the validation of a quantitative high performance liquid chromatography-photodiode array (HPLC-PDA) method for the simultaneous analysis, in mouse plasma, of eperisone hydrochloride and paracetamol by protein precipitation using zinc sulphate-methanol-acetonitrile. The analytes were resolved on a Gemini C18 column (4.6 mm × 250 mm; 5 μm particle size) using a gradient elution mode with a run time of 15 min, comprising re-equilibration, at 60°C (± 1°C). The method was validated over the concentration range from 0.5 to 25 μg/mL for eperisone hydrochloride and paracetamol, in mouse plasma. Ciprofloxacin was used as Internal Standard. Results from assay validations show that the method is selective, sensitive and robust. The limit of quantification of the method was 0.5 μg/mL for eperisone hydrochloride and paracetamol, and matrix-matched standard curves showed a good linearity, up to 25 μg/mL with correlation coefficients (r(2))≥ 0.9891. In the entire analytical range the intra and inter-day precision (RSD%) values were ≤ 1.15% and ≤ 1.46% for eperisone hydrochloride, and ≤ 0.35% and ≤ 1.65% for paracetamol. For both analytes the intra and inter-day trueness (bias%) values ranged, respectively, from -5.33% to 4.00% and from -11.4% to -4.00%. The method was successfully tested in pharmacokinetic studies after oral administration in mouse. Furthermore, the application of this method results in a significant reduction in terms of animal number, dosage, and improvement in speed, rate of analysis, and quality of pharmacokinetic parameters related to serial blood sampling. Copyright © 2015 Elsevier B.V. All rights reserved.

A Population Pharmacokinetic Model for Disposition in Plasma, Saliva and Urine of Scopolamine after Intranasal Administration to Healthy Human Subjects

Science.gov (United States)

Wu, L.; Tam, V. H.; Chow, D. S. L.; Putcha, L.

2014-01-01

An intranasal gel formulation of scopolamine (INSCOP) was developed for the treatment of Space Motion Sickness. The bioavailability and pharmacokinetics (PK) were evaluated under the Food and Drug Administration guidelines for clinical trials with an Investigative New Drug (IND) protocol. The aim of this project was to develop a PK model that can predict the relationship between plasma, saliva and urinary scopolamine concentrations using data collected from the IND clinical trials with INSCOP. Methods: Twelve healthy human subjects were administered three dose levels (0.1, 0.2 and 0.4 mg) of INSCOP. Serial blood, saliva and urine samples were collected between 5 min and 24 h after dosing and scopolamine concentrations were measured by using a validated LC-MS-MS assay. Pharmacokinetic Compartmental models, using actual dosing and sampling times, were built using Phoenix (version 1.2). Model selection was based on the likelihood ratio test on the difference of criteria (-2LL) and comparison of the quality of fit plots. Results: The best structural model for INSCOP (minimal -2LL= 502.8) was established. It consisted of one compartment each for plasma, saliva and urine, respectively, which were connected with linear transport processes except the nonlinear PK process from plasma to saliva compartment. The best-fit estimates of PK parameters from individual PK compartmental analysis and Population PK model analysis were shown in Tables 1 and 2, respectively. Conclusion: A population PK model that could predict population and individual PK of scopolamine in plasma, saliva and urine after dosing was developed and validated. Incorporating a non-linear transfer from plasma to saliva compartments resulted in a significantly improved model fitting. The model could be used to predict scopolamine plasma concentrations from salivary and urinary drug levels, allowing non-invasive therapeutic monitoring of scopolamine in space and other remote environments.

The sequential organ failure assessment (SOFA) score is an effective triage marker following staggered paracetamol (acetaminophen) overdose.

Science.gov (United States)

Craig, D G; Zafar, S; Reid, T W D J; Martin, K G; Davidson, J S; Hayes, P C; Simpson, K J

2012-06-01

The sequential organ failure assessment (SOFA) score is an effective triage marker following single time point paracetamol (acetaminophen) overdose, but has not been evaluated following staggered (multiple supratherapeutic doses over >8 h, resulting in cumulative dose of >4 g/day) overdoses. To evaluate the prognostic accuracy of the SOFA score following staggered paracetamol overdose. Time-course analysis of 50 staggered paracetamol overdoses admitted to a tertiary liver centre. Individual timed laboratory samples were correlated with corresponding clinical parameters and the daily SOFA scores were calculated. A total of 39/50 (78%) patients developed hepatic encephalopathy. The area under the SOFA receiver operator characteristic for death/liver transplantation was 87.4 (95% CI 73.2-95.7), 94.3 (95% CI 82.5-99.1), and 98.4 (95% CI 84.3-100.0) at 0, 24 and 48 h, respectively, postadmission. A SOFA score of paracetamol overdose, is associated with a good prognosis. Both the SOFA and APACHE II scores could improve triage of high-risk staggered paracetamol overdose patients. © 2012 Blackwell Publishing Ltd.

Saliva levels of Abeta1-42 as potential biomarker of Alzheimer's disease: a pilot study

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Antequera Desiree

2010-11-01

Full Text Available Abstract Background Simple, non-invasive tests for early detection of degenerative dementia by use of biomarkers are urgently required. However, up to the present, no validated extracerebral diagnostic markers for the early diagnosis of Alzheimer disease (AD are available. The clinical diagnosis of probable AD is made with around 90% accuracy using modern clinical, neuropsychological and imaging methods. A biochemical marker that would support the clinical diagnosis and distinguish AD from other causes of dementia would therefore be of great value as a screening test. A total of 126 samples were obtained from subjects with AD, and age-sex-matched controls. Additionally, 51 Parkinson's disease (PD patients were used as an example of another neurodegenerative disorder. We analyzed saliva and plasma levels of β amyloid (Aβ using a highly sensitive ELISA kit. Results We found a small but statistically significant increase in saliva Aβ42 levels in mild AD patients. In addition, there were not differences in saliva concentration of Aβ42 between patients with PD and healthy controls. Saliva Aβ40 expression was unchanged within all the studied sample. The association between saliva Aβ42 levels and AD was independent of established risk factors, including age or Apo E, but was dependent on sex and functional capacity. Conclusions We suggest that saliva Aβ42 levels could be considered a potential peripheral marker of AD and help discrimination from other types of neurodegenerative disorders. We propose a new and promising biomarker for early AD.

A high performance liquid chromatographic assay of Mefloquine in saliva after a single oral dose in healthy adult Africans

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Gbotosho Grace O

2012-02-01

Full Text Available Abstract Background Mefloquine-artesunate is a formulation of artemisinin based combination therapy (ACT recommended by the World Health Organization and historically the first ACT used clinically. The use of ACT demands constant monitoring of therapeutic efficacies and drug levels, in order to ensure that optimum drug exposure is achieved and detect reduced susceptibility to these drugs. Quantification of anti-malarial drugs in biological fluids other than blood would provide a more readily applicable method of therapeutic drug monitoring in developing endemic countries. Efforts in this study were devoted to the development of a simple, field applicable, non-invasive method for assay of mefloquine in saliva. Methods A high performance liquid chromatographic method with UV detection at 220 nm for assaying mefloquine in saliva was developed and validated by comparing mefloquine concentrations in saliva and plasma samples from four healthy volunteers who received single oral dose of mefloquine. Verapamil was used as internal standard. Chromatographic separation was achieved using a Hypersil ODS column. Results Extraction recoveries of mefloquine in plasma or saliva were 76-86% or 83-93% respectively. Limit of quantification of mefloquine was 20 ng/ml. Agreement between salivary and plasma mefloquine concentrations was satisfactory (r = 0.88, p Conclusion Disposition of mefloquine in saliva paralleled that in plasma, making salivary quantification of mefloquine potentially useful in therapeutic drug monitoring.

Oral versus intravenous paracetamol: which is better in closure of patent ductus arteriosus in very low birth weight infants?

Science.gov (United States)

Sancak, Selim; Gokmen Yildirim, Tulin; Topcuoglu, Sevilay; Yavuz, Taner; Karatekin, Guner; Ovali, Fahri

2016-01-01

To compare the efficacy of oral and intravenous paracetamol for closure of hemodynamically significant patent ductus arteriosus (HSPDA) in very low birth weight (VLBW) preterm infants. Eighteen VLBW infants with HSPDA treated with either intravenous (n = 10) or oral (n = 8) paracetamol at 60 mg/kg/d for three consecutive days were analysed retrospectively. Ductal closure rate and evaluation of liver function tests were the major outcomes. After two courses of treatment, HSPDA closure rate was higher in oral paracetamol group than that in the intravenous paracetamol group (88% versus 70%), but it was not statistically significant (p = 0.588). Liver function tests were normal after the treatment. Although it was not statistically significant, the cumulative closure rates were higher in oral paracetamol group than those in the intravenous group. Larger trials are needed to confirm these data.

Comparison between Infusion Pumps: Fentanyl/Ketamine and Fentanyl/Paracetamol in Pain control Following Tight and Leg Surgeries

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Behnam Mahmoodiyeh

2016-08-01

Full Text Available Background: Adjuvants such as ketamine, promethazine and paracetamol could bring up patients satisfaction and control harmful effects of opioids besides lessening their needed doses, as seen by fentanyl/paracetamol and fentanyl/ketamine combination before. The current study headed to compare paracetamol and ketamine in addition to fentanyl applied by infusion pumps in order to pain relief following major surgery.Methods: Through a double blinded randomized clinical trial, patients between18 and 65 with elective surgery for tight or leg fractures with ASA Class 1 and 2 referring to a university hospital in Arak, a town in central region of Iran, were recruited and used infusion pump for their postoperative pain control. The participants were divided into cases and controls regarding using ketamine/fentanyl (KF or paracetamol/fentanyl (PF infusion pumps.Results: The mean pain score was totally 3.87 with higher value in KF (5.06 and lower in PF (4.5 immediately after finishing surgery and getting conscious when started using infusion pump. There was no statistical difference between the groups in this regard. Concerning the side effects of the applied medications, blood pressure and heart rate had no differences comparing the groups.Conclusion: This study showed that paracetamol used in infusion pump can be brilliant in pain control after major surgeries like what done in lower extremities and joint replacement while lessens opioid use. Although paracetamol was more effective than ketamine in the current trial, more qualified studies at bigger size and in other fields of surgery beside orthopedic ones would be useful to support the effects if applicable.Keywords: Infusion pump, Ketamine, Paracetamol, Fentanyl, Postoperative pain

The haemodynamic effects of intravenous paracetamol (acetaminophen) in healthy volunteers: a double‐blind, randomized, triple crossover trial

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Chiam, Elizabeth; Bailey, Michael; McNicol, Larry; Bellomo, Rinaldo

2016-01-01

Aim The haemodynamic effects of intravenous paracetamol have not been systematically investigated. We compared the physiological effects of intravenous mannitol‐containing paracetamol, and an equivalent dosage of mannitol, and normal saline 0.9% in healthy volunteers. Methods We performed a blinded, triple crossover, randomized trial of 24 adult healthy volunteers. Participants received i.v. paracetamol (1 g paracetamol +3.91 g mannitol 100 ml–1), i.v. mannitol (3.91 g mannitol 100 ml–1) and i.v. normal saline (100 ml). Composite primary end points were changes in mean arterial pressure (MAP), systolic blood pressure (SBP) and diastolic blood pressure (DBP) measured pre‐infusion, during a 15 min infusion period and over a 45 min observation period. Systemic vascular resistance index (SVRI) and cardiac index were measured at the same time points. Results Infusion of paracetamol induced a transient yet significant decrease in blood pressures from pre‐infusion values (MAP –1.85 mmHg, 95% CI –2.6, –1.1, SBP –0.54 mmHg, 95% CI –1.7, 0.6 and DBP −1.92 mmHg, 95% CI –2.6, –1.2, P paracetamol caused a transient decrease in blood pressure immediately after infusion. These effects were not seen with mannitol or normal saline. The physiological mechanism was consistent with vasodilatation. This study provides plausible physiological data in a healthy volunteer setting, supporting transient changes in haemodynamic variables with i.v. paracetamol and justifies controlled studies in the peri‐operative and critical care setting. PMID:26606263

Saliva transit in patients with gastroesophageal reflux disease.

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Cassiani, R A; Mota, G A; Aprile, L R O; Dantas, R O

2015-10-01

Saliva is an important factor in the neutralization of the acidity of the refluxed material that comes from the stomach to the esophagus. The impairment of saliva transit from oral cavity to distal esophagus may be one of the causes of esophagitis and symptoms in gastroesophageal reflux disease (GERD). With the scintigraphic method, the transit of 2 mL of artificial saliva was measured in 30 patients with GERD and 26 controls. The patients with GERD had symptoms of heartburn and acid regurgitation, a 24-hour pH monitoring with more than 4.2% of the time with pH below four, 26 with erosive esophagitis, and four with non-erosive reflux disease. Fourteen had mild dysphagia for solid foods. Twenty-one patients had normal esophageal manometry, and nine had ineffective esophageal motility. They were 15 men and 15 women, aged 21-61 years, mean 39 years. The control group had 14 men and 12 women, aged 19-61 years, mean 35 years. The subjects swallowed in the sitting and supine position 2 mL of artificial saliva labeled with 18 MBq of (99m) Technetium phytate. The time of saliva transit was measured from oral cavity to esophageal-gastric transition, from proximal esophagus to esophageal-gastric transition, and the transit through proximal, middle, and distal esophageal body. There was no difference between patients and controls in the time for saliva to go from oral cavity to esophageal-gastric transition, and from proximal esophagus to esophageal-gastric transition, in the sitting and supine positions. In distal esophagus in the sitting position, the saliva transit duration was shorter in patients with GERD (3.0 ± 0.8 seconds) than in controls (7.6 ± 1.7 seconds, P = 0.03). In conclusion, the saliva transit from oral cavity to the esophageal-gastric transition in patients with GERD has the same duration than in controls. Saliva transit through the distal esophageal body is faster in patients with GERD than controls. © 2014 International Society for Diseases of the

Tramadol-Paracetamol Combination for Postoperative Pain Relief in Elective Single-level Microdisectomy Surgery.

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Dogar, Samie A; Khan, Fauzia A

2017-04-01

The tramadol and paracetamol combination is used frequently for postoperative pain management. The literature on the use of this combination for vertebral surgery is limited. Our objective was to compare a combination of paracetamol 1 g and a lower dose of tramadol (1 mg/kg: group 1T) with a combination of paracetamol 1 g and a higher dose of tramadol (1.5 mg/kg: group 1.5T) for postoperative pain after microdisectomy surgery. Our main outcome measure was Visual Analogue Scale pain scores for 4 hours postoperatively. This prospective randomized triple-blind clinical trial was conducted at Aga Khan University Hospital, Karachi. Ninety-four patients aged between 18 and 50 years scheduled for elective single-level microdisectomy were allocated randomly into 1 of 2 groups. Twenty minutes before the end of the surgery, patients received the study drugs. There was no significant demographic difference between groups. None of the patients experienced severe pain (VAS>6). There was no significant difference in the mean pain score between groups. The mean score at 4 hours was 2.17 (1.38) in group 1.5T and 1.74 (1.37) in group 1T. The difference was not statistically significant (P=0.14). In group 1.5T, 13 patients reported having nausea and vomiting compared with 2 patients in group 1T. This was a statistically significant difference (P=0.004). The sedation score was similar between groups. The combination of low-dose tramadol (1 mg/kg) and paracetamol has comparable analgesia and a decreased incidence of nausea and vomiting compared with the higher dose of tramadol (1.5 mg/kg) and paracetamol combination.

Saliva as a tool for monitoring steroid, peptide and immune markers in sport and exercise science.

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Papacosta, Elena; Nassis, George P