SMA-TB: study protocol for the phase 2b randomized double-blind, placebo-controlled trial to estimate the potential efficacy and safety of two repurposed drugs, acetylsalicylic acid and ibuprofen, for use as adjunct therapy added to, and compared with, the standard WHO recommended TB regimen.

BACKGROUND: The duration and regimen of tuberculosis (TB) treatment is currently based predominantly on whether the M. tuberculosis (Mtb) strain is drug-sensitive (DS) or multidrug-resistant (MDR) with doses adjusted by patients' weight only. The systematic stratification of patients for personalized treatment does not exist for TB. As each TB case is different, individualized treatment regimens should be applied to obtain better outcomes. In this scenario, novel therapeutic approaches are urgently needed to (1) improve outcomes and (2) shorten treatment duration, and host-directed therapies (HDT) might be the best solution. Within HDT, repurposed drugs represent a shortcut in drug development and can be implemented at the short term. As hyperinflammation is associated with worse outcomes, HDT with an anti-inflammatory effect might improve outcomes by reducing tissue damage and thus the risk of permanent sequelae. METHODS: SMA-TB is a multicentre randomized, phase IIB, placebo-controlled, three-arm, double-blinded clinical trial (CT) that has been designed in the context of the EC-funded SMA-TB Project ( www.smatb.eu ) in which we propose to use 2 common non-steroidal anti-inflammatory drugs (NSAID), acetylsalicylic acid (ASA) and ibuprofen (Ibu), as an HDT for use as adjunct therapy added to, and compared with, the standard of care (SoC) World Health Organization (WHO)-recommended TB regimen in TB patients. A total of 354 South African and Georgian adults diagnosed with confirmed pulmonary TB will be randomized into SoC TB treatment + placebo, SoC + acetylsalicylic acid or SoC + ibuprofen. DISCUSSION: SMA-TB will provide proof of concept of the HDT as a co-adjuvant treatment and identify the suitability of the intervention for different population groups (different epidemiological settings and drug susceptibility) in the reduction of tissue damage and risk of bad outcomes for TB patients. This regimen potentially will be more effective and targeted: organ saving, reducing tissue damage and thereby decreasing the length of treatment and sequelae, increasing cure rates and pathogen clearance and decreasing transmission rates. It will result in better clinical practice, care management and increased well-being of TB patients. TRIAL REGISTRATION: Clinicaltrials.gov NCT04575519. Registered on October 5, 2020.

Hyperbaric oxygen treatment in a rare complication of intramuscular injection: four cases of Nicolau syndrome.

Intramuscular injections are one of the most common clinical procedures. The objectives of this case series are to analyse the role, timing and efficacy of hyperbaric oxygen treatment (HBOT) in the management of Nicolau syndrome (NS), an extremely rare complication of this common intervention. Clinical, demographic, laboratory and microbiological data extraction were performed through retrospective analysis of the medical records of all patients with NS who were referred for HBOT over a 10-year period with wounds, ischaemia, infection or necrosis at the injection site following drug injection; four patients with NS were included. All injections were made via the intramuscular route; three adult cases followed a non-steroidal anti-inflammatory drug, diclofenac sodium and one in a child followed penicillin injection. The time between diagnosis/injection and HBOT ranged from five to 33 days. NS can develop despite all preventive measures based on injection technique guidelines. HBOT appeared beneficial to healing of NS when administered with other therapeutic approaches. Due to the missing pieces of the puzzle in pathogenesis, NS is rarely completely reversible; keeping the awareness high for undesirable complications stands out as the most effective approach.

Proposed Canadian Consensus Guidelines on Osteoarthritis Treatment Based on OA-COAST Stages 1-4.

The Canadian consensus guidelines on OA treatment were created from a diverse group of experts, with a strong clinical and/or academic background in treating OA in dogs. The document is a summary of the treatment recommendations made by the group, with treatments being divided into either a core or secondary recommendation. Each treatment or modality is then summarized in the context of available research based support and clinical experience, as the treatment of OA continues to be a multimodal and commonly a multidisciplinary as well as individualized approach. The guidelines aim to help clinicians by providing clear and clinically relevant information about treatment options based on COAST defined OA stages 1-4.

Acciones cardiovasculares directas del paracetamol / Direct cardiovascular actions of paracetamol

Introducción: El paracetamol es uno de los antiinflamatorios no esteroideos con efecto analgésico y antipirético más utilizados a nivel mundial. Pocos estudios se enfocan en esclarecer los mecanismos de acción a nivel cardiovascular. Objetivos: Evaluar la acción del paracetamol sobre la fuerza de contracción de anillos de aorta torácica y sobre la actividad eléctrica y contráctil de corazones aislados y perfundidos de ratas Wistar. Métodos: Se midieron los efectos del paracetamol sobre anillos de aorta de rata denudados de su endotelio vascular. Se estudiaron las acciones del fármaco sobre los corazones aislados y perfundidos de las ratas por el método de Langendorff. Se evaluó la amplitud de la fuerza de contracción cardiaca y los intervalos QT, QTc, QRS y RR del electrocardiograma. Las condiciones (control y presencia de paracetamol) fueron comparadas con una prueba t de Student para muestras pareadas (p < 0,05), previa comprobación de la normalidad de los datos. Resultados: El paracetamol no tuvo efectos sobre el músculo liso vascular de los anillos aórticos ni sobre los intervalos QT, QTc, QRS y RR del electrocardiograma bajo ninguna de las concentraciones empleadas. Por otra parte, mostró efecto inotrópico negativo estadísticamente significativo en los corazones aislados, de forma dependiente de la concentración del fármaco. La IC50 estimada para la inhibición de la fuerza de contracción cardiaca fue de 17,15 ± 5,33 µmol/L. Conclusiones: Las acciones cardiovasculares directas del paracetamol son modestas, lo cual contribuye al buen margen de seguridad para su uso en clínica, en pacientes sin enfermedad cardiovascular(AU)

Introduction: Paracetamol is among the non-steroidal anti-inflammatory, analgesic and antipyretic drugs most commonly used worldwide. Few studies have focused on clarifying its mechanisms of action on a cardiovascular level. Objectives: Evaluate the action of paracetamol on the force of contraction of thoracic aortic rings and on the electrical and contractile activity of isolated perfused Wistar rat hearts. Methods: Measurements were taken of the effects of paracetamol on rat aortic rings denuded of their vascular endothelium. Analysis was performed of the actions of the drug on the isolated perfused rat hearts using the Langendorff method. Evaluation was conducted of the amplitude of the force of cardiac contraction and of intervals QT, QTc, QRS and RR of the electrocardiogram. The conditions (control and presence of paracetamol) were compared with a paired samples Student's t-test (p < 0.05) upon verification of the normality of the data. Results: Paracetamol had no effects on the vascular smooth muscle of aortic rings or on intervals QT, QTc, QRS and RR of the electrocardiogram at none of the concentrations used. On the other hand, it displayed a statistically significant negative inotropic effect on the isolated hearts dependent on drug concentration. The IC50 estimated for inhibition of the force of cardiac contraction was 17.15 ± 5.33 µmol/L. Conclusions: The direct cardiovascular actions of paracetamol are modest, which contributes to a good safety margin for its clinical use in patients without cardiovascular disease(AU)

Photobiomodulation as oedema adjuvant in post-orthognathic surgery patients: A randomized clinical trial.

OBJECTIVE: Photobiomodulation therapy (PBMT) has been used in multiple applications in general medicine as powerful anti-inflammatory, analgesic and reducing oedema in different parts of the body. The aim of this study is to compare the effect on post-surgical oedema after mandibular orthognathic surgery, between two different laser power densities and oral medication with non-steroidal anti-inflammatory. MATERIALS AND METHODS: In a randomized clinical trial, on 60 patients who were subject to mandibular orthognathic surgery were divided into three groups. All groups received sodium naproxen 250mg every 8hours for 6days. Two groups were irradiated with two different laser application protocols and the other was a control group. In G1 group the irradiation parameters three times per week for two weeks were: 940nm, in continuous mode, 2.5W, 120s, 85.71J/cm2, 0.89W/cm2, over the right and left side with a distance from the skin surface of 1mm with the whitening handpiece (spot size of 2.8cm2). In G2, the irradiation parameters three times a week for two weeks were: 940nm, in continuous mode, 4.1W, 120s, 68.33J/cm2, 0.58W/cm2 over the right and left side with a distance from the skin surface of 15mm, with the deep tissue handpiece (spot size of 7.1cm2). In all the groups, millimetric facial measurements were taken from tragus to lateral commissure, and from lateral commissure to gonion in both sides. RESULTS: All differences between T1 and T6 were significant for the three groups, (paired T, P<0.05). The differences between the groups were generally not significant (P>0.05) except for commissure - right and left gonion when compared G1 vs CG (P<0.05) and G2 vs CG (P<0.05). Initial changes (T1-T2) between groups were significantly different except for the measurement from commissure to right tragus G1 vs CG (P=0.411) and from commissure to left tragus G2 vs CG (P=0.94). The faster resolution of the oedema occurred in G2 group. PTBM with an energy density of 68.33J/cm2 was the most effective adjuvant to oral medication with non-steroidal anti-inflammatory, to decrease post-surgical oedema after mandibular orthognathic surgery.

Efetividade do controle da dor no tratamento ortodôntico: ensaio clínico controlado e randomizado / Effectiveness of orthodontic treatment pain control: a randomized and controlled trial

Objetivo geral consistiu em comparar a efetividade analgésica de ibuprofeno, acetaminofeno e goma de mascar na redução da dor ortodôntica. O objetivo secundário consistiu em avaliar se o uso de goma de mascar poderia ser uma alternativa não farmacológica de controle da dor após inserção do primeiro arco ortodôntico. Cento e seis pacientes foram consecutivamente selecionados, assinaram Termo de Consentimento Livre e Pós Informado e randomicamente distribuídos na proporção de 1:1:1:1 em um dos quatro grupos amostrais: a) ibuprofeno; b) acetaminofeno; c) goma de mascar; d) controle. Os pacientes alocados no grupo ibuprofeno e acetaminofeno foram orientados a ingerirem respectivamente 400 mg e 500 mg dos medicamentos imediatamente após a inserção do arco ortodôntico inicial, e de 6/6 horas por uma semana caso a dor persistisse. O grupo goma de mascar foi orientado a mascar um tablete de goma de mascar por cinco minutos após a inserção do arco ortodôntico inicial e de 6/6 horas por cinco minutos durante uma semana em caso de dor. Os pacientes do grupo controle não receberam nenhum método de controle da dor, mas também não foram proibidos de fazerem uso de analgésicos. Eles receberam orientação de informar caso algum medicamento fosse utilizado durante a pesquisa. A experiência de dor dos pacientes foi registrada em escalas visuais analógicas de 100 mm de comprimento (EVAs), que partiam de um ponto denominado "sem dor" e terminavam em "dor exagerada", nos seguintes intervalos de tempo: T1-2 horas, T2-24 horas, T3-2 dias, T4-3 dias, T5-7 dias e T6-21 dias após a consulta de colagem de bráquetes e tubos de slots 0,022"x0,028" na arcada superior até primeiros molares, prescrição edgewise Roth e inserção fio metálico de liga de níquel-titânio de calibre 0,014". O registro das experiências de dor, em cada intervalo de tempo, foi realizado em dois momentos: dor espontânea e em dor durante o apertamento, quando os dentes posteriores inferiores iam de encontro aos antagonistas. Os questionários foram recolhidos e as EVAs mensuradas por um único avaliador previamente calibrado (Sx=1,38%). Teste estatístico de Kruskall Wallis foi aplicado para análise intra grupos e teste de Mann Whitney U post hoc para análise entre os grupos, considerando-se intervalo de confiança de 95%, nível de significância de 5% e penalização de Bonferroni. Assim pôde-se concluir que ibuprofeno, acetaminofeno e controle não apresentaram entre si diferenças estatisticamente significantes no alívio da dor ortodôntica em nenhum intervalo de tempo; observou-se também que os pacientes que utilizaram goma de mascar apresentaram menor experiência de dor quando comparados com os pacientes do grupo controle que não fizeram uso de métodos de controle da dor ortodôntica.

The main objective of the present study was to evaluate the analgesic effectiveness of ibuprofen, actemaninophen and chewing gum on orthodontic pain reduction. The secondary objective was to assess the use of chewing gum as a non-pharmacological alternative for pain control after initial archwire placement. One hundred and six patients were consecutively selected, signed the Free and Post-Informed Term of Consent, and randomly allocated in a ratio of 1:1:1: 1 at four sample groups: a) ibuprofen; b) acetaminophen; c) chewing gum; d) control group. Patients on the ibuprofen and acetaminophen group were instructed to ingest 400 mg and 500 mg respectively of the drugs immediately after the initial archwire placement and every 6 hours for one week if the pain persisted. The subjects on the chewing gum group were instructed to chew a tablet of gum (Trident®-Mondelez, Bauru-SP, Brazil) for five minutes after the initial archwire placement and five minutes every 6 hours for one week if the pain persisted. The control group subjects received no method of pain control. They were required to report the use of any analgesic throughout the trial period. The patients registered their experienced pain while at mandible rest position (spontaneous pain) and at maximum intercuspation (pain at mastication) in 100mm Visual Analogic Scales (VAS), starting at "no pain" and ending at "unbearable pain", at T1-2 hours, T2-24 hours, T3-2 days, T4-3 days, T5-7 days, and T6-21 days after bonding of tubes and brackets 0.022"x0.028", edgewise Roth prescription from 1.6 to 2.6 and nickel-titanium 0.014"achwire placement. VAS data were collected by one previously calibrated evaluator (Sx= 1.38%). Kruskal Wallis test was applied for intragroup analysis and Mann Whitney U post hoc for between groups analysis, with a 95% interval of confidence and 5% of significance level and Bon Ferroni penalizations. Thus, there were no statistically significant differences at pain relief among subjects from ibuprofen, acetaminophen and control groups. But subjects in the chewing gum group experienced statistically significant pain relief when compared to the control group.

Serum sodium changes in marathon participants who use NSAIDs.

INTRODUCTION: The primary mechanism through which the development of exercise-associated hyponatraemia (EAH) occurs is excessive fluid intake. However, many internal and external factors have a role in the maintenance of total body water and non-steroidal anti-inflammatory medications (NSAIDs) have been implicated as a risk factor for the development of EAH. This study aimed to compare serum sodium concentrations ([Na]) in participants taking an NSAID before or during a marathon (NSAID group) and those not taking an NSAID (control group). METHODS: Participants in a large city marathon were recruited during race registration to participate in this study. Blood samples and body mass measurements took place on the morning of the marathon and immediately post marathon. Blood was analysed for [Na]. Data collected via questionnaires included athlete demographics, NSAID use and estimated fluid intake. RESULTS: We obtained a full data set for 28 participants. Of these 28 participants, 16 took an NSAID on the day of the marathon. The average serum [Na] decreased by 2.1 mmol/L in the NSAID group, while it increased by 2.3 mmol/L in the control group NSAID group (p=0.0039). Estimated fluid intake was inversely correlated with both post-marathon serum [Na] and ∆ serum [Na] (r=-0.532, p=0.004 and r=-0.405 p=0.032, respectively). CONCLUSION: Serum [Na] levels in participants who used an NSAID decreased over the course of the marathon while it increased in those who did not use an NSAID. Excessive fluid intake during a marathon was associated with a lower post-marathon serum [Na].

Acute kidney injury associated with endurance events-is it a cause for concern? A systematic review.

INTRODUCTION: A growing body of evidence suggests even small rises in serum creatinine (SCr) are of considerable clinical relevance. Given that participants in endurance events are exposed to potential (repeated) renal insults, a systematic review was undertaken to collate current evidence for acute kidney injury (AKI), complicating such events. METHODS: A systematic review of studies and case reports meeting inclusion criteria on Medline and EMBASE (inception to October 2015). Included: studies with markers of renal function before and after endurance or ultraendurance events; case reports of severe AKI. Two reviewers assessed risk of bias using the Newcastle-Ottawa scale. RESULTS: Eleven case report publications (n=27 individuals) of severe AKI, were retrieved, with risk factors including systemic illness or nephrotoxic medications usually identified. From 30 studies of endurance and ultraendurance events, mean rise in SCr was 29 (±12.3) µmol/L after marathon or ultramarathon (17 studies, n=568 participants) events. Where follow-up tests were conducted, SCr returned to baseline within 48 hours. Rises in biomarkers suggest potential parenchymal insult, rather than simply muscle breakdown. However, evidence of long-term deleterious effects is lacking. CONCLUSIONS: Raised levels of SCr are reported immediately after endurance events. It is not clear whether this is either clinically significant, or if repeated participation predisposes to long-term sequelae. The aetiology of severe exercise-associated AKI is usually multifactorial, with risk factors generally identified in the rare cases reported. On-site biochemistry, urine analysis and biomarkers of AKI may help identify collapsed runners who are at significant short-term risk and allow suitable follow-up.

An effective microfluidic based liquid-phase microextraction device (µLPME) for extraction of non-steroidal anti-inflammatory drugs from biological and environmental samples.

In this work, the traditional liquid phase microextraction (LPME) has been miniaturized into a microfluidic device (µLPME) where liquid phase microextraction is combined with an HPLC procedure. This integration enables extraction and determination of acid drugs by µLPME and HPLC, respectively. The analytes selected for the test are five widely used non-steroidal anti-inflammatory drugs (NSAIDs): salicylic acid (SAC), ketoprofen (KTP), naproxen (NAX), diclofenac (DIC) and ibuprofen (IBU). They have successfully been detected in biological (urine and saliva) and environmental (lake and river water) samples with excellent clean up, high extraction efficiency and good enrichment factor under stopped-flow conditions. The µLPME consists of two small channels (acceptor and donor channel) separated by a support liquid membrane and has been implemented to allow a simple membrane replacement an arbitrary number of times. The sample (pH 12) and acceptor phase (pH 1.5) are delivered to the µLPME at 1 µL min-1 flow rate and the extraction is completed after 6 min. Under these conditions, the recoveries obtained in urine samples are over 87% for all compounds. For environmental water analysis, different types of water samples have been analyzed obtaining recoveries over 75% for all compounds. The sample consumption is dramatically decreased (<7 µL) as compared to traditional LPME. This confirms the advantages of the here proposed µLPME when using small volume/high cost samples. Finally, when the acceptor flow is turned off during the extraction time, high enrichment factor significantly increases with the extraction time for all compounds. As an example, the IBU is enriched by a factor of 75 after 25 min extraction consuming only 500 µL of sample.

Patterns of anti-inflammatory drug use and risk of dementia: a matched case-control study.

BACKGROUND AND PURPOSE: There is limited primary-care-based evidence about a potential association between anti-inflammatory therapy and dementia subtypes. The present study addressed this limitation by using electronic health records from a large primary care database. METHOD: A case-control study was implemented using electronic medical records. Cases had a diagnosis of dementia between 1992 and 2014. Up to four controls matched on age, gender, family practice and index date were selected for each case. Use of non-steroidal anti-inflammatory drugs (NSAIDs) and glucocorticoid drugs represented the exposure variables. Primary outcome measures included all-cause dementia and main dementia subtypes, including Alzheimer disease (AD), vascular dementia (VaD) and Lewy body dementia (LBD). Data were analysed using conditional logistic regression. RESULTS: The study identified 31,083 patients with AD, 23,465 with VaD and 1694 with LBD. Ever-used NSAIDs were associated with a modest increase in the risk of all-cause dementia (odds ratio 1.04, 95% confidence interval 1.02-1.05, P < 0.006), whilst no association was apparent for ever-used glucocorticoids (0.98, 0.96-1.01, P = 0.152). There was no evidence for an association between NSAIDs and AD (1.03, 0.99-1.06, P = 0.07) or LBD (1.13, 0.99-1.29, P = 0.08). However, a significant increase in the risk for VaD (1.33, 1.29-1.38, P < 0.001) was observed. Similar patterns emerged for glucocorticoid therapy. CONCLUSION: In a large primary care population, there was no robust evidence for a potential association between anti-inflammatory drugs and risk of AD or LBD. NSAIDs and glucocorticoid drugs were associated with higher risk of VaD.

Impact of discontinuing non-steroidal antiinflammatory drugs on long-term recurrence in colonic diverticular bleeding.

AIM: To determine the effect of discontinuing non-steroidal antiinflammatory drugs (NSAIDs) on recurrence in long-term follow-up patients with colonic diverticular bleeding (CDB). METHODS: A cohort of 132 patients hospitalized for CDB examined by colonoscopy was prospectively enrolled. Comorbidities, lifestyle, and medications (NSAIDs, low-dose aspirin, antiplatelet agents, anticoagulants, acetaminophen, and corticosteroids) were assessed. After discharge, patients were requested to visit the hospital on scheduled days during the follow-up period. The Kaplan-Meier method was used to estimate recurrence. RESULTS: Median follow-up was 15 mo. The probability of recurrence at 1, 6, 12, and 24 mo was 3.1%, 19%, 27%, and 38%, respectively. Of the 41 NSAID users on admission, 26 (63%) discontinued NSAID use at discharge. Many of the patients who could discontinue NSAIDs were intermittent users, and could be switched to alternative therapies, such as acetaminophen or an antiinflammatory analgesic plaster. The probability of recurrence at 12 mo was 9.4% in discontinuing NSAID users compared with 77% in continuing users (P<0.01, log-rank test). The hazard ratio for recurrence in the discontinuing NSAIDs users was 0.06 after adjusting for age>70 years, right-sided diverticula, history of hypertension, and hemodialysis. No patients developed cerebrocardiovascular events during follow-up. CONCLUSION: There is a substantial recurrence rate after discharge among patients hospitalized for diverticular bleeding. Discontinuation of NSAIDs is an effective preventive measure against recurrence. This study provides new information on risk reduction strategies for diverticular bleeding.

Molecular interactions between some non-steroidal anti-inflammatory drugs (NSAID's) and bovine (BSA) or human (HSA) serum albumin estimated by means of isothermal titration calorimetry (ITC) and frontal analysis capillary electrophoresis (FA/CE).

The interactions between some non-steroidal anti-inflammatory drugs, NSAIDs, (naproxen, ibuprofen and flurbiprofen) and bovine (BSA) or human (HSA) serum albumin have been examined by means of two complementary techniques, isothermal titration calorimetry (ITC) and frontal analysis/capillary electrophoresis (FA/CE). It can be concluded that ITC is able to measure with high precision the strongest drug-albumin interactions but the higher order interactions can be better determined by means of FA/CE. Then, the combination of both techniques leads to a complete evaluation of the binding profiles between the selected NSAIDs and both kind of albumin proteins. When BSA is the binding protein, the NSAIDs show a strong primary interaction (binding constants: 1.5 × 10(7), 8 × 10(5) and 2 × 10(6) M(-1) for naproxen, ibuprofen and flurbiprofen, respectively), and also lower affinity interactions of the same order for the three anti-inflammatories (about 1.7 × 10(4) M(-1)). By contrast, when HSA is the binding protein two consecutive interactions can be observed by ITC for naproxen (9 × 10(5) and 7 × 10(4) M(-1)) and flurbiprofen (5 × 10(6) and 6 × 10(4) M(-1)) whereas only one is shown for ibuprofen (9 × 10(5) M(-1)). Measurements by FA/CE show a single interaction for each drug being the ones of naproxen and flurbiprofen the same that those evaluated by ITC as the second interaction events. Then, the ability of both techniques as suitable complementary tools to establish the whole interaction NSAIDs-albumin profile is experimentally demonstrated and allows foreseeing suitable strategies to establish the complete drug-protein binding profile. In addition, for the interactions analyzed by means of ITC, the thermodynamic signature is established and the relative contributions of the enthalpic and entropic terms discussed.

Toxicity assessments of nonsteroidal anti-inflammatory drugs in isolated mitochondria, rat hepatocytes, and zebrafish show good concordance across chemical classes.

To reduce costly late-stage compound attrition, there has been an increased focus on assessing compounds in in vitro assays that predict attributes of human safety liabilities, before preclinical in vivo studies are done. Relevant questions when choosing a panel of assays for predicting toxicity are (a) whether there is general concordance in the data among the assays, and (b) whether, in a retrospective analysis, the rank order of toxicity of compounds in the assays correlates with the known safety profile of the drugs in humans. The aim of our study was to answer these questions using nonsteroidal anti-inflammatory drugs (NSAIDs) as a test set since NSAIDs are generally associated with gastrointestinal injury, hepatotoxicity, and/or cardiovascular risk, with mitochondrial impairment and endoplasmic reticulum stress being possible contributing factors. Eleven NSAIDs, flufenamic acid, tolfenamic acid, mefenamic acid, diclofenac, meloxicam, sudoxicam, piroxicam, diflunisal, acetylsalicylic acid, nimesulide, and sulindac (and its two metabolites, sulindac sulfide and sulindac sulfone), were tested for their effects on (a) the respiration of rat liver mitochondria, (b) a panel of mechanistic endpoints in rat hepatocytes, and (c) the viability and organ morphology of zebrafish. We show good concordance for distinguishing among/between NSAID chemical classes in the observations among the three approaches. Furthermore, the assays were complementary and able to correctly identify "toxic" and "non-toxic" drugs in accordance with their human safety profile, with emphasis on hepatic and gastrointestinal safety. We recommend implementing our multi-assay approach in the drug discovery process to reduce compound attrition.

Efeito do uso profilático do anti-inflamatório não-esteroide ibuprofeno sobre o desempenho em uma sessão de treino de força / Effects of prophylactic anti-inflammatory non-steroidal ibuprofen on performance in a session of strength training

INTRODUÇÃO: Medicamentos anti-inflamatórios não esteroides, como o ibuprofeno, têm sido utilizados por atletas de várias modalidades com o intuito de aumentar desempenho esportivo. OBJETIVO: Verificar o efeito do uso profilático de ibuprofeno sobre desempenho em uma sessão de treino de força. MÉTODOS: Um ensaio clínico, cruzado, randomizado, duplo-cego e placebo-controlado foi desenvolvido com 12 praticantes regulares de treino de força do sexo masculino, os quais realizaram uma sessão de treino após a ingestão de ibuprofeno (1,2 g) e uma outra após a ingestão de placebo. Seis séries dos exercícios supino e agachamento foram realizadas em cada sessão de treino com uma carga constante correspondente a 65% da 1RM de cada exercício. O desempenho no treinamento foi mensurado através do número de repetições que os voluntários conseguiram realizar em cada série de exercício a cada sessão de treino de força. RESULTADOS: Não foram verificadas diferenças significativas de desempenho no treino de força com a administração prévia de placebo ou ibuprofeno (p > 0,05). CONCLUSÃO: A ingestão de ibuprofeno nos parâmetros de administração adotados pelo presente estudo não promove qualquer tipo de alteração na tolerância ao exercício em uma sessão isolada de treino de força, o que contraria a indicação dessa substância para fins ergogênicos no treino de força.

INTRODUCTION: Non-steroidal anti-inflammatory drugs, such as ibuprofen, have been used by athletes of several sports modalities in order to increase athletic performance. OBJECTIVE: To verify the effect of the prophylactic use of ibuprofen on performance in a strength training session. METHODS: A crossover, randomized, double-blind and placebo-controlled clinical assay was developed with twelve male regular practitioners of strength training who performed one strength training session after ibuprofen (1.2 g) ingestion and another session after placebo ingestion. Six series of bench press and squat exercises were performed in each training session with constant load corresponding to 65% of the 1RM in each exercise. The training performance was measured through the number of repetitions that volunteers have accomplished in each exercise series of each strength training session. RESULTS: No significant performance differences were verified in strength training with previous administration of placebo or ibuprofen (p < 0.05). CONCLUSION: Ibuprofen administration at the same parameters adopted by the present study does not promote any change on tolerance to exercise in a single strength training session, a fact which is contrary to the administration of this substance for ergogenic purposes in strength training.