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Aspergillus niger prolyl endoprotease (AN-PEP) efficiently degrades gluten molecules into non-immunogenic peptides in vitro.
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Several studies have shown that colchicine exhibits an improvement in the symptoms of knee osteoarthritis (OA) but its effect on disease progression is unknown. To clarify the mechanism of action this study was done to see if colchicine prevents degradation of collagen fiber network in OA by studying serum cartilage oligomeric matrix protein (COMP) levels, a marker of cartilage turnover, over a period of 1 year.
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In a prospective open-label trial, seven patients with Churg-Strauss syndrome refractory to cyclophosphamide or methotrexate received interferon-alpha (3 million. I.U. 3 times weekly s.c.) for induction of remission. Primary end point was the successful induction of remission. Prednisolone was tapered according to the study protocol.
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Physiologically based pharmacokinetic (PBPK) modeling of the central nervous system (CNS) provides the opportunity to predict the relevant drug concentrations at the therapeutic target site during preclinical and clinical development. In order to successfully interpret model results, and to provide confidence in the subsequent human predictions, it is essential that an appropriate model structure is chosen at the preclinical stage which takes into account both physiological and drug-specific knowledge. However, the models published to date in the literature show significant variation in the approaches applied by different authors, which can lead to difficulties in the interpretation of model parameter estimates. We aimed to develop a coherent PBPK modeling approach in the rat, which would also be adaptable depending on the quantity and quality of in vivo data obtained during drug development. Based on a sensitivity analysis of the model parameters, and using three CNS drugs as case studies (atomoxetine, acetaminophen, and S 18986), we proposed a decision tree to aid in the appropriate parametrization and structure of the model according to the data available. We compared our parameter estimates to those originally published, and considered the impact of the respective approaches on the mechanistic interpretation of the parameter values. Since the measurement of brain extracellular fluid (ECF) concentrations using microdialysis is not routinely performed in the industrial environment, we also evaluated the bottom-up scaling of in vitro permeability data from the Caco-2 cell line to predict BBB passive permeability in the absence of measured ECF concentrations. Our strategy demonstrates the value of PBPK as a prediction tool throughout the development process of CNS-targeting drugs.
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Derangement in 5-HT(2A) serotonin receptor has been reported to implicate in pathogenesis of medication-overuse headache. No clear explanation concerning the precise roles of these receptors in the process.
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Multimodal postoperative analgesia employs multiple medications given perioperatively to block the generation and perception of pain at different points in the nociceptive pathway. This retrospective study examines its effect on the length of stay for patients undergoing hindfoot and ankle fusions.
A single preoperative oral dose of pregabalin, acetaminophen, dextromethorphan, and naproxen one hour before surgery is an effective method for reducing postoperative pain and morphine consumption in patients undergoing radical neck dissection.
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The writing of prescriptions is an important aspect of medical practice. This activity presents some specific problems given a danger of misinterpretation and dispensing errors in community pharmacies. The objective of this study was to determine the evolution of the prescription practice and writing quality in the outpatient clinics of our paediatric university hospital.
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The influence of temperature (20-40 °C) on the acetaminophen adsorption onto activated carbons with different textures was studied. Different temperature dependences, not explained by kinetic effects, were observed for carbons with different micropore size distribution patterns: adsorption capacity increased for pine gasification residues (Pi-fa) derived carbons and decreased for sisal based materials. No significant variation was seen for carbon CP. The species identified by (1)H NMR spectroscopy on the back-extraction solution proved that during the adsorption process exist the conditions required to promote the formation of acetaminophen oligomers which have constrained access to the narrow microporosity. The rotation energy of the dihedral angle between monomers (estimated by electronic DFT methods) showed that conformations in the planar form are less stable than the non-planar conformation (energy barrier of 70 and 23 kJ mol(-1)), but have critical dimensions similar to the monomer and can access most of the micropore volume. The enthalpy change of the overall process showed that the energy gain of the system (endothermic) for Pi-fa samples (≈40 kJ mol(-1)) was enough to allow a change in the dimer, or even a larger oligomer, conformation to the planar form. This will permit adsorption in the narrow micropores, thus explaining the uptake increase with temperature. Non-continuous micropore size distributions centered at pore widths close to the critical dimensions of the planar form seem to be crucial for a positive evolution of the adsorption capacity with temperature.
This study aimed to compare the effects of morphine and diclofenac suppositories on postoperative pain management.
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There were 9,212 cases of toxic exposures during the study period, which constituted 0.94% of total ED attendances. The poison exposure rate was 1.7 per 1,000 population and the estimated case fatality rate was 0.8 per 1,000 ED attendances for poisoning. The mean age of patients was 29 years and the majority were male (63.3%). Non-accidental injuries constituted 60% of the cohort. Alcohol was the commonest toxin involved (26%), but paracetamol (acetaminophen) was the most common pharmaceutical agent (33%). The mean time of exposure to ED presentation was 3.3 h. About one third of the patients were admitted of whom 157 patients (4.7% of admitted cases) required intensive care management.
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Maximal movement-evoked pain intensity over the first two postoperative days (P = 0.38) failed to predict the presence of CPSP 6 months later after controlling for age (P = 0.09), treatment group (P = 0.91), and cumulative morphine consumption (P = 0.8) (multivariate logistic regression likelihood ratio test against the intercept only model P = 0.59).
We have designed gel formulations for the oral administration of paracetamol with suitable rheological characteristics for ease of administration to patients with swallowing difficulties and sufficient integrity in the acidic environment of the stomach to achieve a sustained release of this drug.
Nimesulide is a non-steroidal anti-inflammatory drug with antipyretic and analgesic properties, which is still used in many countries despite its known hepatotoxicity. Along with hepatotoxicity it has also been associated with several other Adverse Drug Reactions (ADRs) including leukocytoclastic vasculitis (LCV).
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We conducted a retrospective revision study between January 2010 and December 2014. We included all patients admitted to the Emergency Department of the University General Hospital of Elche with a diagnosis of uncomplicated acute diverticulitis based on medical history, physical examination and abdominopelvic computed tomography (CT) scanning. Outpatient treatment consisted of oral antibiotics for 10 days (metronidazole 500 mg/8 h and ciprofloxacin 500 mg/12 h), a liquid diet and oral analgesics (acetaminophen 1 g/6 h).
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Viscous fibers, including beta-glucan in oat bran, favorably affect satiety as well as postprandial carbohydrate and lipid metabolism. However, effects of fiber viscosity on modulation of satiety-related gut hormone responses are largely unknown. We examined the effects of modified oat bran, with or without its natural viscosity, on sensations of appetite and satiety-related gastrointestinal (GI) hormone responses to establish the relevance of viscosity of beta-glucan in oat bran. Twenty healthy, normal-weight participants (16 female, 4 male, aged 22.6 +/- 0.7 y) ingested 2 isocaloric (1250 kJ) 300-mL oat bran beverages with low or high viscosity (carbohydrates, 57.9 g; protein, 7.8 g; fat, 3.3 g; fiber, 10.2 g) after a 12-h fast in randomized order. Viscosity of the low-viscosity oat bran beverage was reduced by beta-glucanase treatment. Blood samples were drawn before and 15, 30, 45, 60, 90, 120, and 180 min after beverage consumption. The oat bran beverage with low viscosity induced a greater postprandial increase in satiety (P = 0.048) and plasma glucose (P < 0.001), insulin (P = 0.008), cholecystokinin (P = 0.035), glucagon-like peptide 1 (P = 0.037), and peptide YY (P = 0.051) and a greater decrease in postprandial ghrelin (P = 0.009) than the beverage with high-viscosity oat bran. Gastric emptying as measured by paracetamol absorption was also faster (P = 0.034) after low-viscosity oat bran beverage consumption. In conclusion, viscosity differences in oat beta-glucan in a liquid meal with identical chemical composition strongly influenced not only glucose and insulin responses, but also short-term gut hormone responses, implying the importance of food structure in the modulation of postprandial satiety-related physiology.
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The mean+/-SD age of the women was 20.4+/-2.0 years; the mean age of menarche was 12.3+/-1.5 years. A total of 64% of the women experienced dysmenorrhea. Dysmenorrhea was more prevalent among nutrition and psychology students than among medicine, pharmacy and dentistry students (p<0.05). Dysmenorrhea was mild in 36.1% of women, moderate in 43.8% and severe in 20.1%. Nursing students showed an intensity of pain that was significantly higher than that of medicine and dentistry students (p<0.05). Sixty-five percent of the women with dysmenorrhea reported that it limited their daily activities, and 42.1% reported school absenteeism (SA) as a result. Of those who experienced dysmenorrhea, 25.9% consulted a physician, and 61.7% practiced self-medication (SM). The most common medications used were an over-the-counter (OTC) medication with paracetamol (an analgesic), pamabrom (a diuretic), and pyrilamine (a histamine antagonist), another OTC with metamizol (a non-steroidal anti-inflammatory drug [NSAID]) plus butylhioscine (an antispasmodic drug) and naproxen (a NSAID). Of those women using prescribed medications, 18.4% reported complete remission of their symptoms, while 78.1% reported little to moderate alleviation, and 3.6% reported no effect on their menstrual distress. Similarly, of the women who practiced SM, 23.4% reported complete relief, 75.5% reported little to moderate effectiveness, and 1.0% reported no efficacy.
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To investigate the efficiency of Capparis ovata as a protective agent against acute paracetamol toxicity of the liver.
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Two review authors (RN and MO) independently applied predefined criteria to select trials for inclusion and extracted the predefined relevant data, recording methods for randomisation, blinding and exclusions. For the 2016 update a third author (MC) checked all original inclusions, data analyses, and updated the search. Outcomes assessed were seizure recurrence at 6, 12, 18, 24, 36, and 48 months and at age 5 to 6 years in the intervention and non-intervention groups, and adverse medication effects. We assessed the presence of publication bias using funnel plots.
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To evaluate the efficacy and safety of buphenine, aminophenazone and diphenylpyraline hydrochloride when compared with placebo for the control of symptoms associated with common cold in children 6-24 months of age.
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174 OA patients (93%) and 172 orthopaedic surgeons (36%) completed the surveys. Most recommended non-surgical treatments were given to the majority of patients (eg, 80% education about OA, 73% physical therapy, 72% acetaminophen, 80% NSAIDs). However, only 6% of patients and 10% of orthopaedic surgeons reported using a combination of all recommended treatments. Dietary therapy was used least frequently. Only 11% of overweight and 30% of obese participants reported having received dietary therapy and 28% of orthopaedic surgeons reported to prescribe dietary therapy to overweight patients.
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Shoulder pain is a common problem with an estimated prevalence of 4% to 26%. About 1% of adults aged over 45 years consult their GP with a new presentation of shoulder pain every year in the UK. The aetiology of shoulder pain is diverse and includes pathology originating from the neck, glenohumeral joint, acromioclavicular joint, rotator cuff, and other soft tissues around the shoulder girdle. The most common source of shoulder pain is the rotator cuff, accounting for over two-thirds of cases.
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To investigate the protection mechanism of glycyrrhetinic acid towards APAP-induced liver damage using metabolomics method.
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We found low-quality evidence to suggest that single dose aspirin compared with placebo can increase pain relief in women with perineal pain post-episiotomy. Very low-quality evidence also suggested that aspirin can reduce the need for additional analgesia, without increasing maternal adverse effects. Evidence was downgraded based on study limitations (risk of bias), imprecision, and publication bias or both. RCTs excluded breastfeeding women so there is no evidence to assess the effects of aspirin on neonatal adverse effects or breastfeeding.With international guidance recommending mothers initiate breastfeeding within one hour of birth, and exclusively breastfeed for the first six months, the evidence from this review is not applicable to current recommended best practice. Aspirin may be considered for use in non-breastfeeding women with post-episiotomy perineal pain. Although formal assessment was beyond the remit of this review, current guidance suggests that other analgesic drugs (including paracetamol) should be considered first for postpartum perineal pain. Such agents are the focus of other reviews in this series on drugs for perineal pain in the early postpartum period. It is considered most likely that if RCTs are conducted in the future they could compare aspirin with other pain relievers. Future RCTs should be designed to ensure high methodological quality, and address gaps in the evidence, such as the secondary outcomes established for this review. Current research has focused on women with post-episiotomy pain, future RCTs could be extended to women with perineal pain associated with spontaneous tears or operative birth.
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Macrophage activation is implicated in the pathogenesis of the systemic inflammatory response syndrome (SIRS) following paracetamol (acetaminophen) overdose (POD). Neopterin is synthesised from macrophages and reflects the intensity of monocyte/macrophage activation. Soluble CD163 (sCD163) is a marker of alternatively activated M2 macrophages.
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Of our 25 cases with AFHF, acetaminophen toxicity was the most common etiology (nine cases). Twelve of the 25 patients (48%) had cerebral edema on CT, including eight of the nine (89%) with acetaminophen toxicity. Decrease in sulcal markings and ventricular size preceded conspicuous alterations in GWD. Fourteen died, including all 12 with cerebral edema, although death was due to herniation in only one patient. None of the hematological or biochemical variables correlated significantly with mortality.
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It has been observed that acetaminophen shows cardioprotective efficacy in mammals. In this study, we investigated the electromechanical effects of acetaminophen on the left atrium (LA).
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Of 22,728 calls attended to over 3 months, 585 (rate 26/1000 calls) were classified as overdose or self-poisoning. In the 585 patients identified, paracetamol-containing drugs were most commonly involved (31.5%). At least one adverse clinical feature occurred in 103 (17.7%) patients, with higher odds in men and opiate overdose or illegal drugs. Older patients and patients with reduced consciousness were more likely to receive oxygen. The latter also had a greater chance of receiving saline.
This prospective study included all patients admitted to the ED with an osteoarticular injury and a pain score above 30 on the visual analogue scale (VAS). Patients were selected on admission by the reception nurse and given paracetamol within 5 min of admission. VAS scores were recorded 30 and 60 min after admission. On discharge from the ED, the patients underwent a further VAS assessment and were asked a question about pain relief (yes/no answer). The primary endpoint was the VAS score at 60 min. The secondary endpoint was the pain relief expressed by the patient on discharge from the ED.
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We found that regime for day surgical anaesthesia practice varied between as well as within countries. There is obvious room for further research on how to achieve safe and cost-effective logistics and practice for day case surgery.