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OBJECTIVES: This study examined the impact of premedication with ibuprofen and ibuprofen-arginine and the influence of preoperative pain and anxiety on inferior alveolar nerve block (IANB) efficacy in cases of symptomatic irreversible pulpitis. MATERIALS AND METHODS: The study involved 150 SIP patients who were randomly assigned to receive ibuprofen (600 mg), ibuprofen-arginine (1,155 mg), or a placebo 30 min before IANB. Preoperative anxiety and pain levels were assessed using the Modified Dental Anxiety Scale and the Heft-Parker visual scale. IANB efficacy was determined by the absence of or mild pain during the procedure. Statistical analysis included chi-square, z-tests, Analysis of Variance, and Student's t tests. RESULTS: The ibuprofen and ibuprofen-arginine groups exhibited significantly higher IANB success rates (62% and 78%, respectively) compared to the placebo group (34%). However, no significant difference was observed between the ibuprofen and ibuprofen-arginine groups. Patients with successful IANB in the ibuprofen and ibuprofen-arginine groups displayed lower median anxiety scores (8) than those with failed blocks (15) and lower mean preoperative pain scores (118.3). CONCLUSION: In cases of symptomatic irreversible pulpitis the preemptive medication with ibuprofen-arginine effectively increased the efficacy of the inferior alveolar nerve block The inferior alveolar nerve block efficacy was influenced by preoperative anxiety levels and the intensity of pain. CLINICAL RELEVANCE: This research underscores the potential benefits of oral premedication with ibuprofen and ibuprofen-arginine in improving anesthesia outcomes in cases of symptomatic irreversible pulpitis.
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Arginina , Ibuprofeno , Nervo Mandibular , Bloqueio Nervoso , Medição da Dor , Pulpite , Humanos , Pulpite/cirurgia , Ibuprofeno/uso terapêutico , Ibuprofeno/administração & dosagem , Método Duplo-Cego , Masculino , Bloqueio Nervoso/métodos , Feminino , Arginina/uso terapêutico , Arginina/administração & dosagem , Adulto , Anestesia Dentária/métodos , Resultado do Tratamento , Pessoa de Meia-Idade , Combinação de MedicamentosRESUMO
Metamizole, as known as dipyrone or novaminsulfone is widely used, especially in Latin America, for its analgesic and antipyretic function. However, several countries have banned it due to the risk of agranulocytosis, skin necrosis, and other serious adverse effects. To assess the safety of metamizole compared to other commonly used non-opioid analgesics (paracetamol, ibuprofen, and acetylsalicylic acid). An overview of systematic reviews. The searches were performed in the PubMed, Cochrane Library, Embase, Scopus and LILACS databases. Systematic reviews of randomized and nonrandomized clinical trials with adult patients with mild to moderate pain that assessed the adverse effects of metamizole were included. A methodological quality assessment was performed through ROBIS. The protocol of this systematic review was submitted to the International Prospective Register of Systematic Reviews (Prospero, CRD42021295272). Of 387 identified studies, four were included, with a total of 20,643 participants, all submitted to a single dose by oral, intramuscular, or intravenous route. No study reported a serious adverse effect. However, 60 of 778 patients (7.7%) who used metamizole; 120/828 (14.5%) who used acetylsalicylic acid; 56/443 (12.6%) who used paracetamol; and 27/213 (12.7%) who used ibuprofen had mild adverse effects. A complementary statistical analysis showed that metamizole, at any dose, has a 38.8% lower chance of adverse effects compared to paracetamol and 46.8% compared to acetylsalicylic acid. The results shows that metamizole is a safe drug with evidence of a lower incidence of adverse effects compared to paracetamol and acetylsalicylic acid.
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This study describes the interaction of human serum albumin (HSA) with the binol derivative (R)-(+)-3,3'-dibromo-1,1'-bi-2-naphthol (R-BrB), which has its optical activity based on the prohibitive energetic barrier for conversion into the enantiomer (S)-(+)-3,3'-dibromo-1,1'-bi-2-naphthol (S-BrB). The objective was to assess the ability of HSA to differentiate axial enantiomers based on their binding efficiency and their impact on the CD spectra. We discovered that both enantiomers were effective ligands, and the CD signal disappeared when equimolar amounts of R-BrB and S-BrB were simultaneously added, indicating no preference for either enantiomer. The complexation resulted in a significant signal increase at 250 nm and a bathochromic effect at 370 nm. Molecular docking simulations were performed, and the lower energy pose of R-BrB was selected for DFT calculations. The theoretical CD spectra of free and complexed R-BrB were obtained and showed alterations corroborating the experimental results. By comparing the difference spectrum (HSA:R-BrB minus HSA) with the spectrum of free RBrB in water or ethyl alcohol, we concluded that the CD signal intensification was due to the increased solubilization of R-BrB upon binding to HSA.
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Dicroísmo Circular , Simulação de Acoplamento Molecular , Naftóis , Albumina Sérica Humana , Dicroísmo Circular/métodos , Naftóis/química , Albumina Sérica Humana/química , Estereoisomerismo , Humanos , Teoria da Densidade Funcional , Simulação por Computador , Ligação ProteicaRESUMO
Pharmaceuticals and Personal Care Compounds (PPCPs) are contaminants present in wastewater and in the receiving surface waters, which have no regulations and can bring on environmental risks. In this study, we evaluated the presence of six PPCPs in the Oro River Sub-basin (Colombia) and the environmental risk associated with them. We have verified that the monitored rivers show the presence of Ibuprofen, Cephalexin and Carbamazepine; the first ones (Ibuprofen and cephalexin) were those that presented higher concentrations since they are widely prescribed in Colombia. Pharmaceutical compound concentrations in the rivers downstream of the wastewater treatment plants from Floridablanca were higher than in other monitoring sites being a significant point source of contamination. This wastewater treatment plant receives hospital discharges from the city, including internationally recognized clinics accepting patients from different parts of the country. The environmental risk assessment showed that ibuprofen and Cephalexin have a higher impact on aquatic organisms.
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Monitoramento Ambiental , Rios , Poluentes Químicos da Água , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade , Rios/química , Medição de Risco , Colômbia , Preparações Farmacêuticas/análise , Ibuprofeno/análise , Ibuprofeno/toxicidadeRESUMO
OBJECTIVES: The selected kyotorphin derivatives were tested to improve their antimicrobial and antibiofilm activity. The antimicrobial screening of the KTP derivatives were ascertained in the representative strains of bacteria, including Streptococcus pneumoniae, Streptococcus pyogenes, Escherichia coli and Pseudomonas aeruginosa. METHODS: Kyotorphin derivatives, KTP-NH2, KTP-NH2-DL, IbKTP, IbKTP-NH2, MetKTP-DL, MetKTP-LD, were designed and synthesized to improve lipophilicity and resistance to enzymatic degradation. Peptides were synthesized by standard solution or solid-phase peptide synthesis and purified using RP-HPLC, which resulted in >95 % purity, and were fully characterized by mass spectrometry and 1H NMR. The minimum inhibitory concentrations (MIC) determined for bacterial strains were between 20 and 419 µM. The direct effect of IbKTP-NH2 on bacterial cells was imaged using scanning electron microscopy. The absence of toxicity, high survival after infection and an increase in the hemocytes count was evaluated by injections of derivatives in Galleria mellonella larvae. Proteomics analyses of G. mellonella hemolymph were performed to investigate the underlying mechanism of antibacterial activity of IbKTP-NH2 at MIC. RESULTS: IbKTP-NH2 induces morphological changes in bacterial cell, many differentially expressed proteins involved in DNA replication, synthesis of cell wall, and virulence were up-regulated after the treatment of G. mellonella with IbKTP-NH2. CONCLUSION: We suggest that this derivative, in addition to its physical activity on the bacterial membranes, can elicit a cellular and humoral immune response, therefore, it could be considered for biomedical applications.
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Anti-Infecciosos , Endorfinas , Mariposas , Animais , Proteômica , Mariposas/microbiologia , Antibacterianos/farmacologia , Larva , PeptídeosRESUMO
Drug release from hyperbranched Janus dendrimer-drug conjugates and their subsequent activity are influenced by the different drugs in each dendron and the linker. To understand these effects, we synthetized new Janus-type dendrimers of first and second generation. One dendron with 2,2-Bis(hydroxymethyl)propionic acid functionalized with ibuprofen and the second dendron was obtained with 3-aminopropanol-amidoamine and prednisone. The dendrimers were obtained by copper(I)-catalyzed Click azide-alkyne cycloaddition for the formation of a triazole as a dendrimeric nucleus of Janus dendrimer conjugates are reported. The influence of ibuprofen, prednisone, and spacer on cancer activity of Janus dendrimers conjugates is reported. The IC50 values of the anticancer activity on cancer cell lines the Janus dendrimer of second generation was higher in comparison to the first generation dendrimer. Similarly, the anticancer activity was higher compared to the dendron conjugates. Also, no cytotoxic effects of dendrons and dendrimers on non-cancerous kidney COS-7 cell line was observed. The interesting anticancer activity of the prepared prednisone-ibuprofen Janus dendrimer conjugates suggest that the dendrimers could be of potential use as new anticancer drug.
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Antracenos , Antineoplásicos , Dendrímeros , Antineoplásicos/farmacologia , Dendrímeros/farmacologia , Ibuprofeno , Prednisona , Cobre/químicaRESUMO
Perinatal hypoxia-ischemia represents a significant risk to CNS development, leading to high mortality rates, diverse damages, and persistent neurological deficits. Despite advances in neonatal medicine in recent decades, the incidence of HIE remains substantial. Motor deficits can manifest early, while cognitive impairments may be diagnosed later, emphasizing the need for extended follow-up. This review aims to explore potential candidates for therapeutic interventions for hypoxic-ischemic encephalopathy (HIE), with a focus on cognitive deficits. We searched randomized clinical trials (RCT) that tested drug treatments for HIE and evaluated cognitive outcomes. The results included studies on erythropoietin, melatonin, magnesium sulfate, topiramate, and a combination of vitamin C and ibuprofen. Although there are several indications of the efficacy of these drugs among animal models, considering neuroprotective properties, the RCTs failed to provide complete effectiveness in the context of cognitive impairments derived from HIE. More robust RCTs are still needed to advance our knowledge and to establish standardized treatments for HIE.
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In this research work, a series of 16 quinazoline derivatives bearing ibuprofen and an amino acid were designed as inhibitors of epidermal growth factor receptor tyrosine kinase domain (EGFR-TKD) and cyclooxygenase-2 (COX-2) with the intention of presenting dual action in their biological behavior. The designed compounds were synthesized and assessed for cytotoxicity on epithelial cancer cells lines (AGS, A-431, MCF-7, MDA-MB-231) and epithelial non-tumorigenic cell line (HaCaT). From this evaluation, derivative 6 was observed to exhibit higher cytotoxic potency (IC50) than gefitinib (reference drug) on three cancer cell lines (0.034â µM in A-431, 2.67â µM in MCF-7, and 3.64â µM in AGS) without showing activity on the non-tumorigenic cell line (>100â µM). Furthermore, assessment of EGFR-TKD inhibition by 6 showed a discreet difference compared to gefitinib. Additionally, 6 was used to conduct an inâ vivo anti-inflammatory assay using the 12-O-tetradecanoylphorbol-3-acetate (TPA) method, and it was shown to be 5 times more potent than ibuprofen. Molecular dynamics studies of EGFR-TKD revealed interactions between compound 6 and M793. On the other hand, one significant interaction was observed for COX-2, involving S531. The RMSD graph indicated that the ligand remained stable in 50â ns.
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Aminoácidos , Antineoplásicos , Ciclo-Oxigenase 2 , Ensaios de Seleção de Medicamentos Antitumorais , Receptores ErbB , Ibuprofeno , Quinazolinas , Ibuprofeno/farmacologia , Ibuprofeno/química , Ibuprofeno/síntese química , Humanos , Quinazolinas/farmacologia , Quinazolinas/química , Quinazolinas/síntese química , Ciclo-Oxigenase 2/metabolismo , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Relação Estrutura-Atividade , Aminoácidos/química , Aminoácidos/farmacologia , Aminoácidos/síntese química , Estrutura Molecular , Linhagem Celular Tumoral , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/síntese química , Acetato de Tetradecanoilforbol/farmacologia , Proliferação de Células/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/síntese química , Simulação de Acoplamento Molecular , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/síntese química , Sobrevivência Celular/efeitos dos fármacosRESUMO
OBJECTIVE: The application of anti-inflammatories as topical desensitizers before dental bleaching is an approach to reduce bleaching-induced tooth sensitivity (TS). This randomized controlled trial compared the risk and intensity of TS and the color change resulting from in-office dental bleaching after using an experimental desensitizing gel containing ibuprofen and arginine. METHODS: Sixty-two participants with upper canine shades A2 or darker were randomly assigned to either the ibuprofen-arginine desensitizing group or the placebo group. The desensitizing gel was applied for 15 min before in-office bleaching with 35 % hydrogen peroxide gel for 50 min (2 sessions). To assess the absolute risk and intensity of TS, visual (0-10) and numeric rating (0-5) scales were used, and group comparisons were made using the McNemar test, Wilcoxon test, and paired Student t-test (α = 0.05). Color change was evaluated using Vita Classical, Vita Bleachedguide (ΔSGU), and Vita EasyShade (ΔEab, ΔE00, and ΔWID) before and one month after the bleaching procedure. Group comparisons for color change were done using a paired t-test (α = 0.05). RESULTS: The odds ratio for TS was 0.14 [95 % CI 0.02 to 0.6], meaning lower odds of TS for the desensitizing gel. A lower intensity of TS was also observed for the experimental group (p < 0.005) up to 48 h after bleaching. All color evaluation tools demonstrated effective and similar whitening for both groups (p > 0.05). CONCLUSIONS: Using the experimental desensitizing gel containing ibuprofen and arginine effectively reduced the risk and intensity of TS without compromising the bleaching efficacy. CLINICAL RELEVANCE: The topical application of ibuprofen/arginine on the in-office bleaching reduced risk and intensity of bleaching-induced tooth sensitivity.
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Sensibilidade da Dentina , Clareadores Dentários , Clareamento Dental , Humanos , Sensibilidade da Dentina/induzido quimicamente , Sensibilidade da Dentina/prevenção & controle , Clareadores Dentários/efeitos adversos , Ibuprofeno/uso terapêutico , Clareamento Dental/efeitos adversos , Clareamento Dental/métodos , Peróxido de Hidrogênio/efeitos adversos , Compostos de Sódio , Arginina/uso terapêutico , Resultado do TratamentoRESUMO
Among the biological targets extensively investigated to improve inflammation and chronic inflammatory conditions, cyclooxygenase enzymes (COXs) occupy a prominent position. The inhibition of these enzymes, essential for mitigating inflammatory processes, is chiefly achieved through Non-Steroidal Anti-Inflammatory Drugs (NSAIDs). In this work, we introduce a novel method-based on computational molecular docking-that could aid in the structure-based design of new compounds or the description of the anti-inflammatory activity of already-tested compounds. For this, we used eight crystal complexes (four COX-1 and COX-2 each), and each pair had a specific NSAID: Celecoxib, Meloxicam, Ibuprofen, and Indomethacin. This selection was based on the ligand selectivity towards COX-1 or COX-2 and their binding mode. An interaction profile of each NSAID was compiled to detect the residues that are key for their binding mode, highlighting the interaction made by the Me group. Furthermore, we rigorously validated our models based on structural accuracy (RMSD < 1) and (R2 > 70) using eight NSAIDs and thirteen compounds with IC50 values for each enzyme. Therefore, this model can be used for the binding mode prediction of small and structurally rigid compounds that work as COX inhibitors or the prediction of new compounds that are designed by means of a structure-based approach.
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Introducción: El uso de fármacos con potencial cardiotóxico para tratar enfermedades no cardiovasculares coexistentes resulta un agravante evitable. Objetivo: Evaluar la prescripción de 5 fármacos cardiotóxicos en pacientes con enfermedades cardiovasculares. Métodos: Se realizó un estudio descriptivo transversal (enmarcado en los estudios de utilización de medicamentos) de marzo a diciembre de 2020 en el Policlínico Santa Cruz (Artemisa, Cuba), en una población de 234 sujetos con enfermedades cardiovasculares que habían sido tratados con domperidona, azitromicina, ciprofloxacina, ibuprofeno y diclofenaco. Las variables estudiadas fueron: sexo, edad, consumo de fármacos cardiotóxicos, motivo de indicación, enfermedades cardiovasculares, forma farmacéutica, dosis diaria, intervalo de las dosis y duración del tratamiento. Se realizó un análisis estadístico descriptivo. Resultados: Los fármacos más prescritos fueron la azitromicina (n= 63), el ibuprofeno (n= 59) y la ciprofloxacina (n= 57). Sus principales motivos de indicación fueron, respectivamente, la neumonía adquirida en la comunidad (38,1 por ciento), las infecciones de piel y tejidos blandos (28,8 por ciento), y las infecciones del tracto urinario (43,8 por ciento). La principal enfermedad cardiovascular fue la hipertensión arterial. Para los 5 fármacos seleccionados se reportó su esquema terapéutico (forma farmacéutica, dosis diaria, intervalo de dosis y duración del tratamiento). Conclusiones: Aunque en todos los casos el motivo de indicación es el adecuado, los fármacos pueden sustituirse por otros de menor riesgo cardiovascular. En su mayoría, los esquemas terapéuticos son correctos, salvo en los casos de la domperidona (duración prolongada) y el diclofenaco (altas dosis)(AU)
Introduction: The use of drugs with cardiotoxic potential to treat coexisting noncardiovascular diseases results in avoidable aggravation. Objective: To assess the prescription of 5 cardiotoxic drugs in patients with cardiovascular disease. Methods: A cross-sectional descriptive study (framed in the studies of drug utilization) was carried out from March to December 2020 in the Policlínico Santa Cruz (Artemisa, Cuba), in a population of 234 subjects with cardiovascular diseases who had been treated with domperidone, azithromycin, ciprofloxacin, ibuprofen and diclofenac. The variables studied were: sex, age, consumption of cardiotoxic drugs, reason for indication, cardiovascular disease, pharmaceutical form, daily dose, dose interval, and duration of treatment. Descriptive statistical analysis was performed. Results: The most prescribed drugs were azithromycin (n= 63), ibuprofen (n= 59) and ciprofloxacin (n= 57). Their main reasons for indication were, respectively, community-acquired pneumonia (38.1 percent), skin and soft tissue infections (28.8 percent), and urinary tract infections (43.8 percent). The main cardiovascular disease was arterial hypertension. For the 5 selected drugs, their therapeutic scheme (pharmaceutical form, daily dose, dose interval and duration of treatment) was reported. Conclusions: Although in all cases the reason for indication was adequate, the drugs can be substituted by others of lower cardiovascular risk. For the most part, the therapeutic regimens are correct, except in the cases of domperidone (prolonged duration) and diclofenac (high doses)(AU)
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Humanos , Prescrições de Medicamentos , Doenças Cardiovasculares/tratamento farmacológico , Cardiotoxinas/toxicidade , Farmacovigilância , Ciprofloxacina/uso terapêutico , Diclofenaco/uso terapêutico , Ibuprofeno/uso terapêutico , Epidemiologia Descritiva , Estudos Transversais , Azitromicina/uso terapêutico , Domperidona/uso terapêuticoRESUMO
Los niños con lesiones selares y/o supraselares pueden presentar diabetes insípida central con posterior secreción inadecuada de hormona antidiurética. Nosotros observamos, en algunos casos, aumento de la incidencia de poliuria, natriuresis e hiponatremia, tríada diagnóstica del síndrome cerebral perdedor de sal. Aquí comunicamos la evolución de 7 pacientes con antecedentes de daño agudo del sistema nervioso central y diabetes insípida central seguida por síndrome cerebral perdedor de sal. Como tratamiento aportamos secuencialmente fluidos salinos parenterales, cloruro de sodio oral, desmopresina, mineralocorticoides e incluso tiazidas. Ante la persistencia de poliuria con hiponatremia, agregamos ibuprofeno. Como resultado de este esquema terapéutico secuencial, este grupo redujo significativamente los valores de diuresis diaria de 10 ml/kg/h a 2 ml/kg/h en un tiempo promedio de 5 días, normalizando también las natremias (de 161 mEq/L a 143 mEq/L) en un tiempo promedio de 9 días. En ningún caso observamos efectos adversos asociados al tratamiento.
Children with sellar and/or suprasellar lesions may develop central diabetes insipidus with subsequent inappropriate antidiuretic hormone secretion. An increased incidence of polyuria, natriuresis, and hyponatremia has been reported in some cases, which make up the diagnostic triad of cerebral salt wasting syndrome. Here we report the clinical course of 7 patients with a history of acute central nervous system injury and central diabetes insipidus followed by cerebral salt wasting syndrome. Treatment included the sequential use of parenteral saline solution, oral sodium chloride, desmopressin, mineralocorticoids, and even thiazides. Due to persistent polyuria and hyponatremia, ibuprofen was added. As a result of this sequential therapeutic regimen, daily urine output reduced significantly from 10 mL/ kg/h to 2 mL/kg/h over an average period of 5 days, together with a normalization of natremia (from 161 mEq/L to 143 mEq/L) over an average period of 9 days. No treatment-related adverse effects were observed in any case.
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Humanos , Pré-Escolar , Criança , Adolescente , Diabetes Insípido Neurogênico , Hiponatremia/etiologia , Hiponatremia/tratamento farmacológico , Poliúria/complicações , Poliúria/etiologia , Pesquisa , Ibuprofeno/uso terapêuticoRESUMO
The aim of this work was to investigate novel formulations containing diruthenium(II-III)-ibuprofen (RuIbp) metallodrug encapsulated into the chitosan (CT) biopolymer. Microparticles (RuIbp/CT MPs, â¼ 1 µm) were prepared by spray-drying, and RuIbp/CT-crosslinked nanoparticles (NPs) by ionic gelation (RuIbp/CT-TPP, TPP = tripolyphosphate (1), RuIbp/CT-TPP-PEG, PEG = poly(ethyleneglycol (2)) or pre-gel/polyelectrolyte complex method (RuIbp/CT-ALG, ALG = alginate (3)). Ru analysis was conducted by energy dispersive x-ray fluorescence or inductively coupled plasma atomic emission spectroscopy, and physicochemical characterisation by powder x-ray diffraction, electronic absorption and FTIR spectroscopies, electrospray ionisation mass spectrometry, thermal analysis, scanning electron, transition electron and atomic force microscopies, and dynamic light scattering. The RuIbp-loaded nanosystems exhibited encapsulation efficiency â¼ 20-37%, drug loadingâ¼ 10-20% (w/w), hydrodynamic diameter (nm): 103.2 ± 7.9 (1), 91.7 ± 12.6 (2), 270.2 ± 58.4 (3), zeta potential (mV): +(47.7 ± 2.8) (1), +(49.2 ± 3.6) (2), -(28.2 ± 2.0) (3). Nanoformulation (1) showed the highest cytotoxicity with increased efficacy in relation to the RuIbp free metallodrug against U87MG human glioma cells.
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Patent ductus arteriosus (PDA) is frequent in preterm newborns, and its incidence is inversely associated with the degree of prematurity. The first choice of pharmacological treatment is ibuprofen. Several genes, including EPAS1, have been proposed as probable markers associated with a genetic predisposition for the development of PDA in preterm infants. EPAS 1 NG_016000.1:g.84131C>G or rs7557402 has been reported to be probably benign and associated with familial erythrocytosis by the Illumina Clinical Services Laboratory. Other variants of EPAS1 have been previously reported to be benign for familial erythrocytosis because they decrease gene function and are positive for familial erythrocytosis because the overexpression of EPAS1 is a key factor in uncontrolled erythrocyte proliferation. However, this could be inconvenient for ductal closure, since for this process to occur, cell proliferation, migration, and differentiation should take place, and a decrease in EPAS1 gene activity would negatively affect these processes. Single-nucleotide polymorphisms (SNPs) in EPAS1 and TFAP2B genes were searched with high-resolution melting and Sanger sequencing in blood samples of preterm infants with hemodynamically significant PDA treated with ibuprofen at the National Institute of Perinatology. The variant rs7557402, present in the EPAS1 gene eighth intron, was associated with a decreased response to treatment (p = 0.007, OR = 3.53). The SNP rs7557402 was associated with an increased risk of pharmacological treatment failure. A probable mechanism involved could be the decreased activity of the product of the EPAS1 gene.
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Ibuprofen (IBP) is an anti-inflammatory drug found in aquatic environments, potentially toxic for the biota. We exposed the test fish C. decemmaculatus to two environmentally relevant concentrations (50 and 100 µg IBP/L) for 4 and 12 d and evaluated the effect on some biomarkers. Micronucleus test, nuclear abnormality test and comet assay indicated cyto-genotoxicity at both concentrations and exposure periods. Oxidative stress and biochemical biomarkers were not affected, excepting muscle AChE activity for 4 d. Muscle metabolic biomarkers showed significant decrease in ETS, lipid and protein content, while carbohydrate content was not affected. The CEA index increased at the lower IBP concentration for 4 and 12 d, possibly due to changes in body energy reserves. A full-factorial GLM performed to assess the effects of IBP and exposure times showed that the metabolic and genotoxicity biomarkers were the most sensitive to IBP toxicity, mainly at 50 µg IBP/L for 4 d.
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Ciprinodontiformes , Ibuprofeno , Animais , Ibuprofeno/toxicidade , Biota , Ensaio Cometa , Dano ao DNARESUMO
Children with sellar and/or suprasellar lesions may develop central diabetes insipidus with subsequent inappropriate antidiuretic hormone secretion. An increased incidence of polyuria, natriuresis, and hyponatremia has been reported in some cases, which make up the diagnostic triad of cerebral salt wasting syndrome. Here we report the clinical course of 7 patients with a history of acute central nervous system injury and central diabetes insipidus followed by cerebral salt wasting syndrome. Treatment included the sequential use of parenteral saline solution, oral sodium chloride, desmopressin, mineralocorticoids, and even thiazides. Due to persistent polyuria and hyponatremia, ibuprofen was added. As a result of this sequential therapeutic regimen, daily urine output reduced significantly from 10 mL/kg/h to 2 mL/kg/h over an average period of 5 days, together with a normalization of natremia (from 161 mEq/L to 143 mEq/L) over an average period of 9 days. No treatment-related adverse effects were observed in any case.
Los niños con lesiones selares y/o supraselares pueden presentar diabetes insípida central con posterior secreción inadecuada de hormona antidiurética. Nosotros observamos, en algunos casos, aumento de la incidencia de poliuria, natriuresis e hiponatremia, tríada diagnóstica del síndrome cerebral perdedor de sal. Aquí comunicamos la evolución de 7 pacientes con antecedentes de daño agudo del sistema nervioso central y diabetes insípida central seguida por síndrome cerebral perdedor de sal. Como tratamiento aportamos secuencialmente fluidos salinos parenterales, cloruro de sodio oral, desmopresina, mineralocorticoides e incluso tiazidas. Ante la persistencia de poliuria con hiponatremia, agregamos ibuprofeno. Como resultado de este esquema terapéutico secuencial, este grupo redujo significativamente los valores de diuresis diaria de 10 ml/kg/h a 2 ml/kg/h en un tiempo promedio de 5 días, normalizando también las natremias (de 161 mEq/L a 143 mEq/L) en un tiempo promedio de 9 días. En ningún caso observamos efectos adversos asociados al tratamiento.
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Diabetes Insípido Neurogênico , Hiponatremia , Humanos , Criança , Hiponatremia/tratamento farmacológico , Hiponatremia/etiologia , Poliúria/etiologia , Poliúria/complicações , Ibuprofeno/uso terapêutico , PesquisaRESUMO
Homocysteine (Hcy) is a risk factor for neurodegenerative diseases, such as Alzheimer's Disease, and is related to cellular and tissue damage. In the present study, we verified the effect of Hcy on neurochemical parameters (redox homeostasis, neuronal excitability, glucose, and lactate levels) and the Serine/Threonine kinase B (Akt), Glucose synthase kinase-3ß (GSK3ß) and Glucose transporter 1 (GLUT1) signaling pathway in hippocampal slices, as well as the neuroprotective effects of ibuprofen and rivastigmine alone or in combination in such effects. Male Wistar rats (90 days old) were euthanized and the brains were dissected. The hippocampus slices were pre-treated for 30 min [saline medium or Hcy (30 µM)], then the other treatments were added to the medium for another 30 min [ibuprofen, rivastigmine, or ibuprofen + rivastigmine]. The dichlorofluorescein formed, nitrite and Na+, K+-ATPase activity was increased by Hcy at 30 µM. Ibuprofen reduced dichlorofluorescein formation and attenuated the effect of Hcy. The reduced glutathione content was reduced by Hcy. Treatments with ibuprofen and Hcy + ibuprofen increased reduced glutathione. Hcy at 30 µM caused a decrease in hippocampal glucose uptake and GLUT1 expression, and an increase in Glial Fibrillary Acidic Protein-protein expression. Phosphorylated GSK3ß and Akt levels were reduced by Hcy (30 µM) and co-treatment with Hcy + rivastigmine + ibuprofen reversed these effects. Hcy toxicity on glucose metabolism can promote neurological damage. The combination of treatment with rivastigmine + ibuprofen attenuated such effects, probably by regulating the Akt/GSK3ß/GLUT1 signaling pathway. Reversal of Hcy cellular damage by these compounds may be a potential neuroprotective strategy for brain damage.
Assuntos
Fármacos Neuroprotetores , Ratos , Animais , Masculino , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Rivastigmina/farmacologia , Ibuprofeno/farmacologia , Transportador de Glucose Tipo 1/metabolismo , Ratos Wistar , Glicogênio Sintase Quinase 3 beta/metabolismo , Transdução de Sinais , Hipocampo/metabolismo , Glutationa/metabolismo , Glucose/metabolismo , HomocisteínaRESUMO
Abstract The objective of this study was to conduct a systematic review and meta-analysis of relevant randomized control trials (RCTs) to determine the role of ibuprofen, as well as the optimum dose and duration of therapy, in preventing the incidence of heterotopic ossification (HO) after primary total hip arthroplasty (THA). A literature search was performed using the PubMed/MEDLINE and Cochrane Library databases for RCTs that compared the use of ibuprofen versus placebo as prophylaxis for HO in patients after THA. The main outcomes for this study were overall occurrence of HO, occurrence according to the Brooker classification, and gastrointestinal complications. A total of 27 potential articles were identified from the database. Eventually, four trials with 1,153 patients were included in the final analysis. When compared with placebo, the use of ibuprofen is associated with a reduction in the incidence of HO at the 3- and 12-month follow-up appointments, as well as the incidence of Brooker II and III HO (p < 0.05). However, there was no significant difference between the ibuprofen and placebo groups in terms of treatment discontinuation due to gastrointestinal complications or the incidence of Brooker I and IV HO (p > 0.05). The existing data indicates that ibuprofen is safe and efficacious in reducing the total incidence of HO along with Brooker II and III HO at follow-up. However, due to the small number of studies, the conclusions are limited; therefore, more high-quality clinical trials are required to develop guidelines for optimal dose and duration of therapy.
Resumo O objetivo deste estudo foi realizar uma revisão sistemática e metanálise de estudos clínicos randomizados (ECRs) relevantes para determinar o papel do ibuprofeno, sua dose ideal, e a duração do tratamento na prevenção de ossificação heterotópica (OH) após a artroplastia total primária do quadril (ATQ). Uma pesquisa bibliográfica foi feita nos bancos de dados PubMed/MEDLINE e Cochrane Library para a obtenção de ECRs quecomparassem ouso de ibuprofeno edeplacebo como profilaxiaparaOHem pacientes submetidos à ATQ. Os principais desfechos deste estudo foram ocorrência geral de OH, classificação de Brooker da OH, e complicações gastrintestinais. No total, 27 artigos foram identificados nos bancos de dados e 4 estudos, com 1.153 pacientes, foram incluídos na análise final. Em comparação ao placebo, o uso de ibuprofeno reduziu a incidência de OH aos 3 e 12 meses de acompanhamento e a incidência de OH Brooker II e III (p < 0,05). No entanto, não houve diferença significativa entre os grupos que receberam ibuprofeno e placebo em termos de interrupção do tratamento devido a complicações gastrintestinais ou da incidência de OH Brooker I e IV (p > 0,05). Os dados existentes indicam que o ibuprofeno é seguro e eficaz na redução da incidência total de OH e de OH Brooker II e III durante o acompanhamento. No entanto, as conclusões são limitadas devido ao pequeno número de estudos; logo, mais estudos clínicos de alta qualidade são necessários para o desenvolvimento de diretrizes em relação à dose e duração ideal da terapia.
Assuntos
Humanos , Ibuprofeno , Ossificação Heterotópica , Artroplastia de QuadrilRESUMO
Non-steroidal anti-inflammatory drugs (NSAIDs) act as antipyretics, analgesics and anti-inflammatories. Among them, diclofenac and ibuprofen are the most consumed drugs worldwide. During the COVID-19 pandemic, some NSAIDs, such as dipyrone and paracetamol, have been used to alleviate the symptoms of the disease, causing an increase in the concentrations of these drugs in water. However, due to the low concentration of these compounds in drinking water and groundwater, few studies have been carried out on the subject, especially in Brazil. Thus, this study aimed to evaluate the contamination of the surface water, groundwater, and water treated with diclofenac, dipyrone, ibuprofen, and paracetamol at 3 cities (Orocó, Santa Maria da Boa Vista and Petrolândia) in the Brazilian semiarid region, in addition to analyzing the removal of these drugs by conventional water treatment (coagulation, flocculation, sedimentation, filtration and disinfection) in stations to each city. All drugs analyzed were detected in surface and treated waters. In groundwater, only dipyrone was not found. Dipyrone was seen in surface water with a maximum concentration of 1858.02 µg.L-1, followed by ibuprofen (785.28 µg.L-1), diclofenac (759.06 µg.L-1) and paracetamol (533.64 µg.L-1). The high concentrations derive from the increased consumption of these substances during the COVID-19 pandemic. During the conventional water treatment, the maximum removal of diclofenac, dipyrone, ibuprofen and paracetamol was 22.42%; 3.00%; 32.74%; and 1.58%, respectively, which confirms the inefficiency of this treatment in removing drugs. The variation in removal rate of the analyzed drugs is due to the difference in the hydrophobicity of the compounds.