ABSTRACT
Ketoprofen (KTF) and ketorolac (KTL) are among the most primarily used non-steroidal anti-inflammatory drugs (NSAIDs) in humans to alleviate moderate pain and to treat inflammation. Their binding affinity with albumin (the main globular protein responsible for the biodistribution of drugs in the bloodstream) was previously determined by spectroscopy without considering some conventional pitfalls. Thus, the present work updates the biophysical characterization of the interactions of HSA:KTF and HSA:KTL by 1H saturation-transfer difference nuclear magnetic resonance (1H STD-NMR), ultraviolet (UV) absorption, circular dichroism (CD), steady-state, and time-resolved fluorescence spectroscopies combined with in silico calculations. The binding of HSA:NSAIDs is spontaneous, endothermic, and entropically driven, leading to a conformational rearrangement of HSA with a slight decrease in the α-helix content (7.1% to 7.6%). The predominance of the static quenching mechanism (ground-state association) was identified. Thus, both Stern-Volmer quenching constant (KSV) and binding constant (Kb) values enabled the determination of the binding affinity. In this sense, the KSV and Kb values were found in the order of 104 M-1 at human body temperature, indicating moderate binding affinity with differences in the range of 0.7- and 3.4-fold between KTF and KTL, which agree with the previously reported experimental pharmacokinetic profile. According to 1H STD-NMR data combined with in silico calculations, the aromatic groups in relation to the aliphatic moiety of the drugs interact preferentially with HSA into subdomain IIIA (site II) and are stabilized by interactions via hydrogen bonding and hydrophobic forces. In general, the data obtained in this study have been revised and updated in comparison to those previously reported by other authors who did not account for inner filter corrections, spectral backgrounds, or the identification of the primary mathematical approach for determining the binding affinity of HSA:KTF and HSA:KTL.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal , Ketoprofen , Ketorolac , Protein Binding , Serum Albumin, Human , Humans , Ketoprofen/chemistry , Ketoprofen/metabolism , Ketoprofen/pharmacokinetics , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/metabolism , Anti-Inflammatory Agents, Non-Steroidal/pharmacokinetics , Ketorolac/chemistry , Ketorolac/metabolism , Ketorolac/pharmacokinetics , Serum Albumin, Human/chemistry , Serum Albumin, Human/metabolism , Circular Dichroism , Thermodynamics , Spectrometry, Fluorescence , Binding SitesABSTRACT
Toxicological stress in aquatic organisms is caused by the discharge of hundreds of toxic pollutants and contaminants among which the current study concentrates on the toxic effect of non-steroidal anti-inflammatory drug ibuprofen (IBF) and the trace element selenium (Se). In this study, IBF and Se toxicity on freshwater mussel Lamellidens marginalis was studied for 14 days, and in silico predictions for their degradation were made using Molecular modelling and Quantum Mechanical approaches. The degrading propensity of cytochrome c oxidase proteins from Trametes verticillatus and Thauera selenatis (Turkey tail fungi and Gram-negative bacteria) is examined into atom level. The results of molecular modelling study indicate that ionic interactions occur in the T. selenatis-HEME bound complex by Se interacting directly with HEME, and in the T. versicolor-HEME bound complex by IBF bound to a nearby region of HEME. Experimental and theoretical findings suggest that, the toxicological effects of Se and IBF pollution can be reduced by bioremediation with special emphasis on T. versicolor, and T. selenatis, which can effectively interact with Se and IBF present in the environment and degrade them. Besides, this is the first time in freshwater mussel L. marginalis that ibuprofen and selenium toxicity have been studied utilizing both experimental and computational methodologies for their bioremediation study.
Subject(s)
Ibuprofen , Selenium , Water Pollutants, Chemical , Animals , Ibuprofen/toxicity , Ibuprofen/metabolism , Ibuprofen/chemistry , Water Pollutants, Chemical/toxicity , Water Pollutants, Chemical/chemistry , Water Pollutants, Chemical/metabolism , Selenium/toxicity , Selenium/chemistry , Selenium/metabolism , Biodegradation, Environmental , Anti-Inflammatory Agents, Non-Steroidal/toxicity , Anti-Inflammatory Agents, Non-Steroidal/metabolism , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Quantum Theory , Unionidae/metabolism , Bivalvia/drug effects , Bivalvia/metabolism , Models, Molecular , Fresh Water/chemistryABSTRACT
BACKGROUND: The equine gastrointestinal (GI) microbiome has been described in the context of various diseases. The observed changes, however, have not been linked to host function and therefore it remains unclear how specific changes in the microbiome alter cellular and molecular pathways within the GI tract. Further, non-invasive techniques to examine the host gene expression profile of the GI mucosa have been described in horses but not evaluated in response to interventions. Therefore, the objectives of our study were to (1) profile gene expression and metabolomic changes in an equine model of non-steroidal anti-inflammatory drug (NSAID)-induced intestinal inflammation and (2) apply computational data integration methods to examine host-microbiota interactions. METHODS: Twenty horses were randomly assigned to 1 of 2 groups (n = 10): control (placebo paste) or NSAID (phenylbutazone 4.4 mg/kg orally once daily for 9 days). Fecal samples were collected on days 0 and 10 and analyzed with respect to microbiota (16S rDNA gene sequencing), metabolomic (untargeted metabolites), and host exfoliated cell transcriptomic (exfoliome) changes. Data were analyzed and integrated using a variety of computational techniques, and underlying regulatory mechanisms were inferred from features that were commonly identified by all computational approaches. RESULTS: Phenylbutazone induced alterations in the microbiota, metabolome, and host transcriptome. Data integration identified correlation of specific bacterial genera with expression of several genes and metabolites that were linked to oxidative stress. Concomitant microbiota and metabolite changes resulted in the initiation of endoplasmic reticulum stress and unfolded protein response within the intestinal mucosa. CONCLUSIONS: Results of integrative analysis identified an important role for oxidative stress, and subsequent cell signaling responses, in a large animal model of GI inflammation. The computational approaches for combining non-invasive platforms for unbiased assessment of host GI responses (e.g., exfoliomics) with metabolomic and microbiota changes have broad application for the field of gastroenterology. Video Abstract.
Subject(s)
Microbiota , Animals , Horses/genetics , Intestinal Mucosa/metabolism , Metabolome , Feces/microbiology , Anti-Inflammatory Agents, Non-Steroidal/metabolism , Inflammation/metabolism , Phenylbutazone/metabolism , RNA, Ribosomal, 16S/genetics , RNA, Ribosomal, 16S/metabolismABSTRACT
Ibuprofen (IBU) and naproxen (NPX), as widely prescribed non-steroidal anti-inflammatory drugs (NSAIDs), are largely produced and consumed globally, leading to frequent and ubiquitous detection in various aqueous environments. Previously, the microbial transformation of them has been given a little attention, especially with the isolated fungus. A yeast-like Apiotrichum sp. IB-1 has been isolated and identified, which could simultaneously transform IBU (5 mg/L) and NPX (2.5 mg/L) with maximum efficiencies of 95.77% and 88.31%, respectively. For mono-substrate, the transformation efficiency of IB-1 was comparable to that of co-removal conditions, higher than most of isolates so far. IBU was oxidized mainly through hydroxylation (m/z of 221, 253) and NPX was detoxified mainly via demethylation (m/z of 215) as shown by UPLC-MS/MS results. Based on transcriptome analysis, the addition of IBU stimulated the basic metabolism like TCA cycle. The transporters and respiration related genes were also up-regulated accompanied with higher expression of several dehydrogenase, carboxylesterase, dioxygenase and oxidoreductase encoding genes, which may be involved in the transformation of IBU. The main functional genes responsible for IBU and NPX transformation for IB-1 should be similar in view of previous studies, which needs further confirmation. This fungus would be useful for potential bioremediation of NSAIDs pollution and accelerate the discovery of functional oxidative genes and enzymes different from those of bacteria.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal , Biotransformation , Ibuprofen , Naproxen , Ibuprofen/metabolism , Naproxen/metabolism , Anti-Inflammatory Agents, Non-Steroidal/metabolism , Biodegradation, EnvironmentalABSTRACT
Aspirin is a commonly used nonsteroidal anti-inflammatory drug, associated with many adverse effects. The adverse effects of aspirin such as tinnitus, Reye's syndrome and gastrointestinal bleeding are caused due to conversion of aspirin into its active metabolite salicylic acid after oral intake. Glutathione is a naturally occurring antioxidant produced by the liver and nerve cells in the central nervous system. It helps to metabolize toxins, break down free radicles, and support immune function. This study aims to investigate and explore the possibility of inhibiting aspirin to salicylic acid conversion in presence of glutathione at a molecular level using spectroscopic techniques such as UV-Visible absorption, time-Resolved and time-dependent fluorescence and theoretical DFT/ TD-DFT calculations. The results of steady state fluorescence spectroscopy and time-dependent fluorescence indicated that the aspirin to salicylic acid conversion is considerably inhibited in presence of glutathione. Further, the results presented here might have significant clinical implications for individuals with variations in glutathione level.
Subject(s)
Aspirin , Density Functional Theory , Glutathione , Salicylic Acid , Spectrometry, Fluorescence , Aspirin/pharmacology , Aspirin/chemistry , Aspirin/metabolism , Glutathione/metabolism , Glutathione/chemistry , Salicylic Acid/metabolism , Salicylic Acid/chemistry , Salicylic Acid/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/metabolism , Fluorescence , Molecular StructureABSTRACT
Nonsteroidal anti-inflammatory drugs are the most widely used drugs for Parkinson's disease (PD), of which ibuprofen shows positive effects in suppressing symptoms; however, the associated risk needs to be addressed in different pathological stages. Initially, we developed an initial and advanced stage of the Parkinson disease mouse model by intraperitoneal injection of MPTP (20 mg/kg; 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine) for 10 and 20 days, respectively. Subsequently, ibuprofen treatment was administered for 2 months, and a pole test, rotarod test, histology, immunohistochemistry, and western blotting were performed to determine neuronal motor function. Histological analysis for 10 days after mice were injected with MPTP showed the onset of neurodegeneration and cell aggregation, indicating the initial stages of Parkinson's disease. Advanced Parkinson's disease was marked by Lewy body formation after another 10 days of MPTP injection. Neurodegeneration reverted after ibuprofen therapy in initial Parkinson's disease but not in advanced Parkinson's disease. The pole and rotarod tests confirmed that motor activity in the initial Parkinson disease with ibuprofen treatment recovered (p<0.01). However, no improvement was observed in the ibuprofen-treated mice with advanced disease mice. Interestingly, ibuprofen treatment resulted in a significant improvement (p<0.01) in NURR1 (Nuclear receptor-related 1) expression in mice with early PD, but no substantial improvement was observed in its expression in mice with advanced PD. Our findings indicate that NURR1 exerts anti-inflammatory and neuroprotective effects. Overall, NURR1 contributed to the effects of ibuprofen on PD at different pathological stages.
Subject(s)
Neuroprotective Agents , Parkinson Disease , Animals , Mice , Parkinson Disease/metabolism , Ibuprofen/pharmacology , Ibuprofen/therapeutic use , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/metabolism , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , Mice, Inbred C57BL , Disease Models, Animal , 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/metabolism , 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/pharmacology , 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/therapeutic use , Dopaminergic Neurons/metabolism , Dopaminergic Neurons/pathologyABSTRACT
The aim of this study was to assess the long-term effect of exposure to environmentally relevant doses of non-steroidal anti-inflammatory drugs (NSAIDs; ibuprofen, and diclofenac) and 17ß-ethinylestradiol (EE2) on the mouse uterus. NSAID-EE2 mixtures were administered in the drinking water from gestational day 8 until 8 weeks post-birth (i.e., during embryo development, lactation, puberty, and sexual maturity). The incidence of adenomyosis lesions (presence of endometrial glands in the inner myometrium) increased up to 60% in the uterus of 8-week-old exposed females (F1) and to 85% in F2 females (exposed father). Histological analysis revealed aberrant proliferation and apoptosis, vacuolization of epithelial cells, and increased incidence of abnormal glands in the luminal and glandular epithelium in F1 and F2 uteri. Moreover, myofibroblast proportion (alpha-smooth muscle actin (α-SMA) expression analysis) and collagen expression (Picrosirius red stain; a fibrosis hallmark) were increased in F1 and F2 endometrium. Connexin-43 was aberrantly distributed in the endometrial stroma and glands of F1 and F2 uteri. Conversely, uterine 17ß-estradiol and progesterone levels were not affected in F1 and F2 females. These findings demonstrated that in mice, chronic exposure to NSAID and EE2 mixtures at environmental doses intergenerationally affects uterine physiology, particularly the endometrium. It may serve as a model to study the pathophysiology of human adenomyosis.
Subject(s)
Adenomyosis , Female , Mice , Animals , Humans , Adenomyosis/pathology , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/metabolism , Uterus/metabolism , Endometrium/metabolism , Myometrium/metabolismABSTRACT
BACKGROUND: Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are one of the most commonly used groups of medicinal compounds in the world. The wide access to NSAIDs and the various ways of storing them due to their easy accessibility often entail the problem with the stability and durability resulting from the exposure of drugs to external factors. The aim of the research was to evaluate in vitro the mechanism of competition between ibuprofen (IBU) and its degradation products, i.e., 4'-isobutylacetophenone (IBAP) and (2RS)-2-(4- formylphenyl)propionic acid (FPPA) during transport in a complex with fatted (HSA) and defatted (dHSA) human serum albumin. METHODS: The research was carried out using spectroscopic techniques, such as spectrophotometry, infrared spectroscopy and nuclear magnetic resonance spectroscopy. RESULTS: The comprehensive application of spectroscopic techniques allowed, among others, for the determination of the binding constant, the number of classes of binding sites and the cooperativeness constant of the analyzed systems IBU-(d)HSA, IBU-(d)HSA-FPPA, IBU-(d)HSA-IBAP; the determination of the effect of ibuprofen and its degradation products on the secondary structure of albumin; identification and assessment of interactions between ligand and albumin; assessment of the impact of the presence of fatty acids in the structure of albumin and the measurement temperature on the binding of IBU, IBAP and FPPA to (d)HSA. CONCLUSION: The conducted research allowed us to conclude that the presence of ibuprofen degradation products and the increase in their concentration significantly affect the formation of the IBU-albumin complex and thus, the value of the association constant of the drug, changing the concentration of its free fraction in the blood plasma. It was also found that the presence of an ibuprofen degradation product in a complex with albumin affects its secondary structure.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal , Ibuprofen , Protein Binding , Serum Albumin, Human , Ibuprofen/chemistry , Ibuprofen/metabolism , Ibuprofen/pharmacology , Humans , Serum Albumin, Human/chemistry , Serum Albumin, Human/metabolism , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/metabolism , Binding Sites , Acetophenones/chemistry , Acetophenones/metabolismABSTRACT
This study aimed to investigate the changes in clinical parameters of dry eye disease and meibomian gland dysfunction in both the operated and untreated fellow eyes of patients who underwent unilateral cataract surgery with the short-term administration of anti-inflammatory eye drops in the surgical eye. The medical charts of 57 consecutive patients who underwent unilateral cataract surgery and received 1% prednisolone acetate and non-steroidal anti-inflammatory drug (NSAID, 0.1% bromfenac sodium) eye drops were reviewed. The preoperative ocular surface disease index questionnaire score (38.9 ± 20.5) decreased significantly to 15.2 ± 16.4 at post-surgical 1 week and further to 12.8 ± 11.4 after 1 month. Although meibum quality grade increased and corneal sensitivity decreased at 1 week in operated eyes, corneal erosion scores and Sjogren's International Collaborative Clinical Alliance ocular staining scores even improved over a month in the untreated fellow eyes. The tear matrix metalloproteinase (MMP)-9 grade decreased in both operated eyes and untreated fellow eyes after 1 month from surgery. In conclusion, the short-term topical anti-inflammatory treatment using steroid and NSAID eye drops in the operated eye after cataract surgery decreased subjective ocular surface discomfort and improved ocular surface staining scores and tear MMP-9 expression in the untreated fellow eyes.
Subject(s)
Cataract Extraction , Cataract , Dry Eye Syndromes , Humans , Ophthalmic Solutions/therapeutic use , Meibomian Glands/metabolism , Cataract Extraction/adverse effects , Tears/metabolism , Dry Eye Syndromes/drug therapy , Dry Eye Syndromes/etiology , Dry Eye Syndromes/metabolism , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/metabolism , Cataract/metabolismABSTRACT
OBJECTIVES: A profound comprehension of the molecular mechanisms underpinning the enantioselective transdermal permeation of chiral drugs is critical in the design and assessment of transdermal preparations. The primary objective of this study is to investigate the distinct skin permeation behaviors exhibited by enantiomers of non-steroidal anti-inflammatory drugs (NSAIDs) and elucidate the intricate molecular mechanism at play. METHODS: In vitro and in vivo transdermal permeation studies of chiral NSAIDs were performed using transdermal patch and solution system. Chiral interaction between NSAIDs enantiomers and synthesized chiral ceramide present in the skin was characterized to clarify the different transdermal behaviors. RESULTS: The S-enantiomers of NSAIDs exhibited higher permeability through the skin than R-enantiomer in vitro (1.5-fold) and in vivo (2.0-fold), which was attributed to a stronger interaction between S-enantiomer and ceramide caused by more favorable spatial conformations. S-enantiomer required lower activation energy (24.4 kJ/mol) and Gibbs energy (43.3 kJ/mol), which was favorable in forming the H-bond with ceramide in the skin, resulting in more permeation. CONCLUSION: This research furnished an innovative comprehension of the molecular underpinnings governing the enantioselective permeation of drug enantiomers through the skin, fostering the minimization of undesired enantiomer ingestion (distomers) and amplifying therapeutic efficiency.
Subject(s)
Skin Absorption , Skin , Stereoisomerism , Skin/metabolism , Administration, Cutaneous , Anti-Inflammatory Agents, Non-Steroidal/metabolism , CeramidesABSTRACT
Abstract Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used medications associated with nephrotoxicity, especially when used chronically. Factors such as advanced age and comorbidities, which in themselves already lead to a decrease in glomerular filtration rate, increase the risk of NSAID-related nephrotoxicity. The main mechanism of NSAID action is cyclooxygenase (COX) enzyme inhibition, interfering on arachidonic acid conversion into E2 prostaglandins E2, prostacyclins and thromboxanes. Within the kidneys, prostaglandins act as vasodilators, increasing renal perfusion. This vasodilatation is a counter regulation of mechanisms, such as the renin-angiotensin-aldosterone system works and that of the sympathetic nervous system, culminating with compensation to ensure adequate flow to the organ. NSAIDs inhibit this mechanism and can lead to acute kidney injury (AKI). High doses of NSAIDs have been implicated as causes of AKI, especially in the elderly. The main form of AKI by NSAIDs is hemodynamically mediated. The second form of NSAID-induced AKI is acute interstitial nephritis, which may manifest as nephrotic proteinuria. Long-term NSAID use can lead to chronic kidney disease (CKD). In patients without renal diseases, young and without comorbidities, NSAIDs are not greatly harmful. However, because of its dose-dependent effect, caution should be exercised in chronic use, since it increases the risk of developing nephrotoxicity.
Resumo Os anti-inflamatórios não esteroidais (AINEs) são medicamentos comumente utilizados, associados à nefrotoxicidade, sobretudo quando utilizados cronicamente. Fatores como idade avançada e comorbidades, que por si só já levam à diminuição da taxa de filtração glomerular, aumentam o risco de nefrotoxicidade dos AINEs. O principal mecanismo de ação dos AINEs é a inibição da enzima ciclooxigenase (COX), interferindo na conversão do ácido araquidônico em prostaglandinas E2, prostaciclinas e tromboxanos. Nos rins, as prostaglandinas atuam como vasodilatadoras, aumentando a perfusão renal. Essa vasodilatação atua como uma contrarregulação de mecanismos, como a atuação do sistema renina-angiotensina-aldosterona e do sistema nervoso simpático, culminando com uma compensação para assegurar o fluxo adequado ao órgão. O uso de AINEs inibe esse mecanismo, podendo causar lesão renal aguda (LRA). Altas doses de AINEs têm sido implicadas como causas de LRA, especialmente em idosos. A principal forma de LRA por AINEs é a hemodinamicamente mediada. A segunda forma de apresentação da LRA induzida por AINES é a nefrite intersticial aguda, que pode se manifestar com proteinúria nefrótica. O uso de AINEs em longo prazo pode ocasionar doença renal crônica (DRC). Nos pacientes sem doenças renais, jovens e sem comorbidades, os AINEs não apresentam grandes malefícios. Entretanto, por seu efeito dose-dependente, deve-se ter grande cautela no uso crônico, por aumentar risco de desenvolver nefrotoxicidade.
Subject(s)
Humans , Infant, Newborn , Aged , Aged, 80 and over , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Cyclooxygenase Inhibitors/adverse effects , Renal Insufficiency, Chronic/chemically induced , Acute Kidney Injury/chemically induced , Nephritis, Interstitial/chemically induced , Prostaglandins E/metabolism , Proteinuria/chemically induced , Anti-Inflammatory Agents, Non-Steroidal/metabolism , Risk Factors , Cyclooxygenase Inhibitors/metabolism , Renal Insufficiency, Chronic/physiopathology , Acute Kidney Injury/physiopathology , Nephritis, Interstitial/physiopathologyABSTRACT
To fight against metabolic disorders such as insulin resistance, new alimentary behaviors are developed. For instance, hyperproteined, gluten-free, or collagen-enriched diets could be preconized in order to reduce the consequences of obesity. In this aim, this study evaluates the potential effects of warm sea fish collagen peptides (Naticol(R)) on representative metabolic and inflammatory parameters. For that, male C57Bl6/J mice fed with either a chow- (CD) or high-fat diet (HFD) were submitted or not to specific collagen peptides in drinking water (4 g/kg bw/d) for 20 weeks. Weight, body composition, glucose tolerance, and insulin sensitivity were followed up. Effects of fish collagen peptides on various blood parameters reflecting the metabolism status were also measured (free fatty acids, triglycerides, cholesterol, hormones) together with adipocyte inflammation. Results showed that HFD-fed mice supplemented by fish collagen peptides exhibited a significant lower increase in body weight as soon as the twelfth week of treatment whereas no effect of the peptide was observed in CD fed mice. In line with this result, a weaker increase in fat mass in HFD-fed mice supplemented with Naticol(R) at both 9 and 18 weeks of treatment was also observed. In spite of this resistance to obesity promoted by fish collagen peptides treatment, no difference in glucose tolerance was found between groups whereas mice treated with Naticol(R) exhibited a lower basal glycemia. Also, even if no effect of the treatment on adipocyte lipolysis was found, a decrease of inflammatory cytokines was retrieved in collagen-supplemented group arguing for a potential better insulin sensitivity. Altogether, these results need to be completed but are the first describing a benefic role of warm sea fish collagen peptides in a context of metabolic disease paving the route for a potential utilization in human obesity-associated disorders
Subject(s)
Animals , Male , Mice , Anti-Obesity Agents/therapeutic use , Collagen/therapeutic use , Dietary Supplements , Insulin Resistance , Fish Proteins/therapeutic use , Obesity/therapy , Peptide Fragments/therapeutic use , Adipose Tissue/immunology , Adipose Tissue/metabolism , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Anti-Inflammatory Agents, Non-Steroidal/metabolism , Anti-Obesity Agents/adverse effects , Anti-Obesity Agents/metabolism , Collagen/adverse effects , Collagen/metabolism , CytokinesABSTRACT
A large number of researches have led to a substantial growth of knowledge about exercise and oxidative stress. Initial investigations reported that physical exercise generates free radical-mediated damages to cells; however, in recent years, studies have shown that regular exercise can upregulate endogenous antioxidants and reduce oxidative damage. Yet, strenuous exercise perturbs the antioxidant system by increasing the reactive oxygen species (ROS) content. These alterations in the cellular environment seem to occur in an exercise type-dependent manner. The source of ROS generation during exercise is debatable, but now it is well established that both contracting and relaxing skeletal muscles generate reactive oxygen species and reactive nitrogen species. In particular, exercises of higher intensity and longer duration can cause oxidative damage to lipids, proteins, and nucleotides in myocytes. In this review, we summarize the ROS effects and interplay of antioxidants in skeletal muscle during physical exercise. Additionally, we discuss how ROS-mediated signaling influences physical exercise in antioxidant system
Subject(s)
Humans , Animals , Antioxidants/therapeutic use , Exercise , Healthy Lifestyle , Muscle, Skeletal/metabolism , Oxidative Stress , Reactive Oxygen Species/antagonists & inhibitors , Reperfusion Injury/prevention & control , Anti-Inflammatory Agents, Non-Steroidal/metabolism , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Antioxidants/metabolism , Cell Survival , Diet, Healthy , Mitochondria, Muscle , Muscle Fatigue , Muscle, Skeletal/physiopathologyABSTRACT
El osteoma osteoide es una tumoración ósea benigna frecuente cuya manifestación principal es el dolor nocturno que cede habitualmente con antinflamatorios no esteroideos (AINES). Presentamos el caso de una paciente, mujer de 23 años, con un osteoma osteoide en acetábulo izquierdo. Discutimos el manejo clínico y terapéutico de la paciente así como revisamos la bibliografía actual del tema
Osteoid Osteoma is a benign, common and bone-forming tumor whose main symptom is night pain that usually stop with nonsteroidal antiinflammatory drugs (NSAIDs). We present the case of a patient, 23 years old woman, with an Osteoid Osteoma in left acetabulum. The management and treatment are discussed and the current bibliography reviewed
Subject(s)
Humans , Female , Adult , Osteoma, Osteoid/drug therapy , Osteoma, Osteoid , Anti-Inflammatory Agents, Non-Steroidal/metabolism , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/pharmacokinetics , Acetabulum , Acetabulum/injuries , Acetabulum , Hip/pathology , HipABSTRACT
The mandible condylar process cartilage (CP) of Wistar rats is a secondary cartilage and acts as a mandibular growth site. This phenomenon depends on adequate proteins intake and hormone actions, including insulin. Objectives The present study evaluated the morphological aspects and the expression of the insulin receptor (IR) in the cartilage of the condylar process (CP) of rats subjected to protein undernourishment. Material and Methods The nourished group received a 20% casein diet, while the undernourished group (U) received a 5% casein diet. The re-nourished groups, R and RR, were used to assess the effects of re-nutrition during puberty and adulthood, respectively. CPs were processed and stained with picro-sirius red, safranin-O and azocarmine. Scanning electron microscopy and immunohistochemistry were also performed. Results The area of the CP cartilage and the number of cells in the chondroblastic layer decreased in the U group, as did the thickness of the CP layer in the joint and hypertrophic layer. Renourishment during the pubertal stage, but not during the adult phase, restored these parameters. The cell number was restored when re-nutrition occurred in the pubertal stage, but not in the adult phase. The extracellular matrix also decreased in the U group, but was restored by re-nutrition during the pubertal stage and further increased in the adult phase. IR expression was observed in all CPs, being higher in the chondroblastic and hypertrophic cartilage layers. The lowest expression was found in the U and RR groups. Conclusions Protein malnutrition altered the cellularity, the area, and the fibrous cartilage complex, as well as the expression of the IRs. .
Subject(s)
Animals , Mice , Anti-Inflammatory Agents, Non-Steroidal/metabolism , Cyclooxygenase 1/metabolism , /metabolism , Cyclooxygenase Inhibitors/metabolism , Piroxicam/analogs & derivatives , Thiazines/metabolism , Thiazoles/metabolism , Amino Acid Substitution , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Arginine/chemistry , Arginine/genetics , Arginine/metabolism , Binding Sites , Catalytic Domain , Cyclooxygenase 1/chemistry , Cyclooxygenase 1/genetics , /chemistry , /genetics , Cyclooxygenase Inhibitors/chemistry , Hydrogen Bonding , Leucine/chemistry , Leucine/genetics , Leucine/metabolism , Mutation , Piroxicam/chemistry , Piroxicam/metabolism , Protein Structure, Secondary , Serine/chemistry , Serine/genetics , Serine/metabolism , Thiazines/chemistry , Thiazoles/chemistry , Tyrosine/chemistry , Tyrosine/genetics , Tyrosine/metabolism , WaterABSTRACT
No disponible
Subject(s)
Humans , Female , Adolescent , Dysmenorrhea/complications , Dysmenorrhea/diagnosis , Dysmenorrhea/therapy , Diagnosis, Differential , Anti-Inflammatory Agents, Non-Steroidal/metabolism , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Parasympatholytics/therapeutic use , Analgesics/therapeutic use , Estrogens/therapeutic use , Dysmenorrhea/classification , Dysmenorrhea/epidemiology , Dysmenorrhea/etiology , Dysmenorrhea/pathologyABSTRACT
No disponible
Subject(s)
Humans , Male , Female , Pulmonary Disease, Chronic Obstructive/epidemiology , Pulmonary Disease, Chronic Obstructive/prevention & control , Palliative Care/methods , Palliative Care/organization & administration , Palliative Care/standards , Palliative Care/trends , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Palliative Care , Anti-Inflammatory Agents, Non-Steroidal/metabolism , Anti-Inflammatory Agents, Non-Steroidal/pharmacokineticsABSTRACT
El dolor agudo es una respuesta fisiológica de corta duración ante un estímulo adverso, asociada a cirugía, traumatismos o enfermedad aguda. Debe realizarse siempre una correcta valoración, recogiendo la medida de la intensidad por escalas sencillas, rápidas y prácticas. La mejor estrategia de intervención es la que consiga mayor bienestar con mínimos efectos adversos. La propuesta debe tener en cuenta el perfil de riesgo y la comorbilidad. En dolor leve, la primera opción es paracetamol. Cuando el dolor es moderado, los AINE solos o asociados a opioides menores son eficaces, y, si deben evitarse, la asociación de paracetamol con opioides menores es una alternativa válida. La utilización combinada de analgésicos con distinto mecanismo de acción consigue mejor eficacia analgésica con menos toxicidad. No deberían asociarse dos AINE, por la mayor frecuencia de aparición de efectos adversos. Cuando el dolor es intenso, la mayor eficacia analgésica se consigue con opioides potentes. El escalonamiento analgésico prolonga el sufrimiento del paciente (AU)
Acute pain is a physiological short-term response to an adverse stimulus associated with surgery, trauma or acute disease. A correct evaluation should be made, using simple, quick and useful pain intensity scales. The best interventional strategy should be to achieve a greater well-being with the least adverse effects. This should take into account the patient risk profile and the comorbidities. Acetaminophen (paracetamol) is the first option in acute pain treatment. NSAIDs, as monotherapy or associated with weak opioids, are effective for moderate pain. However when they must be avoided, the combination of acetaminophen with weak opioids is a good alternative. A combination of drugs with different mechanisms of action offers a greater analgesic effect with less toxicity. NSAIDs should not be combined due to the higher incidence of adverse events. Strong opioids have a greater analgesic effect for intense pain (AU)
Subject(s)
Humans , Male , Female , Pain/therapy , Analgesics/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Primary Health Care/methods , Primary Health Care/trends , Analgesics, Opioid/therapeutic use , Acetaminophen/therapeutic use , Dipyrone/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/analysis , Anti-Inflammatory Agents, Non-Steroidal/metabolism , /trends , ComorbidityABSTRACT
É indiscutível o papel da dieta e dos alimentos na manutenção da saúde e na redução do risco de DCNT. Estudos epidemiológicos mostram que o aumento do consumo de alimentos de origem vegetal influencia positivamente a saúde, enquanto estudos in vitro e in vivo em modelo animal elucidam os mecanismos pelos quais compostos bioativos não nutrientes, presentes nos alimentos, atuam na manutenção da saúde e na redução do risco de doenças. A modulação da expressão de genes que codificam proteínas envolvidas em vias de sinalização celular ativadas em DCNT é um dos mecanismos de ação dos compostos bioativos, sugerindo que estes possam ser essenciais à manutenção da saúde. A biodisponibilidade dos compostos bioativos de alimentos, as suas rotas metabólicas e o modo de ação de seus metabólitos são importantes fatores no seu efeito nas DCNT. Todos esses aspectos são temas de investigações recentes, cujos resultados contribuem para a compreensão da ocorrência e desenvolvimento das DCNT e da sua relação com a dieta. Essa revisão visou discutir alguns dos mecanismos envolvidos na resposta inflamatória induzida pela obesidade, apresentar os compostos bioativos de alimentos que modulam essa resposta inflamatória e sua relação com o metabolismo desses compostos.
It is largely accepted the important role of food and feeding habits on health maintenance and development of non transmissible chronic diseases (NTCD). Epidemiologic evidences show that increasing vegetable consumption positively impacts health. On the other hand, in vivo and in vitro studies in animals show that non-nutrient bioactive food substances partly explain the role of food on the maintenance of health and on the risk reduction of these diseases. The modulation of gene expression of proteins that are involved in the cellular signaling pathways of NTCD is an important mechanism of the bioactive food substances, indicating their importance in disease prevention. Bioavailability, metabolic routes and the action of the resultant metabolites of bioactive food compounds are important aspects that may affect NTCD. All these aspects have actively been investigated in the last years and resulted in a greater understanding of the beginning, progression and prevention of NTCD. This review aimed at discussing the involved mechanisms of the inflammatory response induced by obesity and the role of bioactive food compounds in modulating such response.
Subject(s)
Animals , Humans , Diet , Food Analysis , Inflammation/etiology , Nutritional Physiological Phenomena/physiology , Obesity/complications , Phenols/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/metabolism , Antioxidants/administration & dosage , Biological Availability , Curcumin/administration & dosage , Curcumin/metabolism , Inflammation Mediators/physiology , Inflammation/metabolism , Obesity/metabolismABSTRACT
Heterotopic ossification or ectopic bone formation represents a widely known complication after surgery involving joint spaces. Posttraumatic heterotopic ossification can be found at any site. The most common postsurgical site is the hip following total hip arthroplasty. This review explores the treatment options to prevent ectopic bone formation after major surgery of hip, especially, the role of radiotherapy (AU)