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Hip International : the Journal of... Mar 2022Heterotopic ossification (HO) is defined as the formation of lamellar bone in extraskeletal soft tissues. HO can be a severe complication after hip arthroplasty but can...
BACKGROUND
Heterotopic ossification (HO) is defined as the formation of lamellar bone in extraskeletal soft tissues. HO can be a severe complication after hip arthroplasty but can possibly be prevented by postoperative treatment with non-steroidal anti-inflammatory drugs (NSAIDs) or radiotherapy. Diclofenac is 1 of the most used drugs in HO prophylaxis because it is effective and long established. However, there is still no uniform therapy regimen in terms of duration, dose and side effect profile regarding the application of diclofenac in HO prevention. We have, therefore, conducted the first systematic review investigating diclofenac for HO prophylaxis after hip arthroplasty. The aim of this study is to assess the efficacy, dose and duration of diclofenac therapy in preventing HO after total hip arthroplasty (THA).
METHODS
According to the PRISMA Guidelines we performed a systematic literature search in EMBASE via Ovid, in MEDLINE via PubMed and in the Cochrane Library addressing all studies in English and German regarding the prophylaxis of HO with diclofenac after THA. We identified 731 potential studies and included 6 randomised controlled trials with 957 patients.
RESULTS
The studies were heterogeneous with regard to duration of therapy, dose, comparative group and follow-up period. The therapy duration ranged from 9 to 42 days, the applied diclofenac doses ranged from 75 mg to 150 mg daily. Patients treated with diclofenac showed a significant reduction in the total incidence of HO regarding to the Brooker Classification compared to placebo and no clinically relevant ossifications occured (Brooker III and IV).
CONCLUSIONS
Diclofenac is efficacious in the prevention of HO and can be used routinely after THA. The existing data indicates that a minimum dose of 75 mg diclofenac per day started on the first postoperative day for a minimum of 9 days is needed to prevent HO with an acceptable incidence of side effects, such as gastrointestinal symptoms.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthroplasty, Replacement, Hip; Diclofenac; Humans; Incidence; Ossification, Heterotopic
PubMed: 33272062
DOI: 10.1177/1120700020978194 -
Polish Journal of Veterinary Sciences Mar 2023The aim of this study was to investigate the cardiotoxic effect of the combination of tilmicosin and diclofenac sodium in sheep. Thirty-two sheep were used and were...
The aim of this study was to investigate the cardiotoxic effect of the combination of tilmicosin and diclofenac sodium in sheep. Thirty-two sheep were used and were randomly divided into four equal groups as tilmicosin (T), diclofenac sodium (D), tilmicosin+diclofenac sodium (TD) and control (C) group. Group T received a single dose of tilmicosin, Group D was administered diclofenac sodium once a day for 3 days, and group TD was administered diclofenac and tilmicosin at the same doses as group T and D. Group C received NaCl in a similar way. The blood samples were taken before dosing and at 4th, 8th, 24th and 72nd hour post-dosing for measurement of cardiac markers such as H-FABP, cTn-I, CK-MB. H-FABP level of group TD was found to be significantly (p⟨0.05) higher than of group C at the 8th, 24th and 72nd hour and group D and T at the 72nd hour. cTn-I and CK-MB levels of group TD were found significantly (p⟨0.05) higher compared with other groups. In conclusion, the combined use of tilmicosin and diclofenac in sheep causes an increase in cardiac biomarkers and it can be stated that this combination of drugs may cause cardiac damage.
Topics: Animals; Sheep; Diclofenac; Fatty Acid Binding Protein 3; Heart; Biomarkers
PubMed: 36961261
DOI: 10.24425/pjvs.2023.145001 -
European Heart Journal. Cardiovascular... Jul 2023To examine the dose dependency of diclofenac's cardiovascular risks.
AIMS
To examine the dose dependency of diclofenac's cardiovascular risks.
METHODS AND RESULTS
Using Danish health registries and the target trial emulation design, we conducted a series of 300 nationwide cohort studies during 1996-2020, each mimicking the strict design criteria of a clinical trial. Adults eligible for inclusion had no recent non-steroidal anti-inflammatory drug prescriptions, contraindications (gastrointestinal diseases, thrombocytopenia, or heart failure), or conditions with low adherence (dementia or psychiatric disease). Diclofenac initiators were compared to healthcare-seeking non-initiators and head-to-head using an approximated high dose of ≥150 mg/day vs. low dose of <150 mg/day. Cox regression was used to compute the incidence rate ratio (IRR) of major adverse cardiovascular events (MACE) within 30 days following initiation. We adjusted for age, sex, calendar period, comorbidity, comedication, and socioeconomic position. Compared with non-initiators (n = 3 789 617), diclofenac initiators (n = 1 894 834) had an approximately 50% increased rate of MACE (IRR 1.53, 95% confidence interval [CI]: 1.43-1.63), reflecting IRRs of 1.54 (95% CI: 1.40-1.69) for myocardial infarction, 1.29 (1.14-1.45) for ischaemic stroke, and 1.92 (1.71-2.16) for cardiac death. The risk increase was observed for most conditions with chronic pain, in particular headache (IRR 5.10, 95% CI: 1.46-17.85). The risk increase was similar for initiators of high- (IRR 1.55, 95% CI: 1.40-1.71) and low-dose diclofenac (IRR 1.52, 1.41-1.63), which was confirmed in a head-to-head analysis (IRR 1.01, 95% CI: 0.90-1.12).
CONCLUSIONS
Initiators of high- and low-dose diclofenac had comparably increased cardiovascular risks. This finding provides evidence against the assumption that low-dose diclofenac is risk-neutral.
Topics: Adult; Humans; Diclofenac; Brain Ischemia; Stroke; Anti-Inflammatory Agents, Non-Steroidal; Cardiovascular System
PubMed: 36921986
DOI: 10.1093/ehjcvp/pvad018 -
Clinical Oral Investigations Mar 2022This study was aimed to compare the effects of 4 biweekly hyaluronan (HA) injection with glucosamine and diclofenac oral administration on TMJ OA patients.
OBJECTIVES
This study was aimed to compare the effects of 4 biweekly hyaluronan (HA) injection with glucosamine and diclofenac oral administration on TMJ OA patients.
MATERIALS AND METHODS
This retrospective cohort study included TMJ OA patients who had the treatment of 4 biweekly HA injection (group HA) or oral glucosamine hydrochloride for 3 months and diclofenac sodium for 2 weeks (group G/D), and had complete data at first-visit, 3 months, 6 months, and 12 months. Clinical signs and symptoms were scored by anamnestic dysfunction index (Ai) and clinical dysfunction index (Di), and condylar bone changes were evaluated by CBCT scoring system.
RESULTS
We included 22 patients in group HA and 20 patients in group G/D. After HA injection, Ai was decreased from 4.3 to 1.6(CI [- 4.0, - 1.4]) at 3-month follow-up, which was smaller than that in group G/D significantly. Di in group HA was declined significantly from 8.1 at first-visit to 3.6 at 3-month follow-up, while Di in group G/D scarcely changed until at 6- and 12-month follow-up. Neither HA injection nor oral glucosamine/diclofenac showed positive effect on the bone of TMJs during follow-ups with statistical significance.
CONCLUSIONS
HA injection alleviated signs and symptoms of TMJ OA rapidly and presented superior clinical effects over oral glucosamine with diclofenac. However, both treatments did not limit the bone destruction of TMJs significantly.
CLINICAL RELEVANCE
This cohort study provides knowledge on the symptom relief and bone changes of TMJ OA patients when treated with HA injection or glucosamine and diclofenac oral administration.
Topics: Cohort Studies; Diclofenac; Glucosamine; Humans; Hyaluronic Acid; Osteoarthritis; Retrospective Studies; Temporomandibular Joint; Temporomandibular Joint Disorders
PubMed: 34705118
DOI: 10.1007/s00784-021-04241-8 -
Molecules (Basel, Switzerland) Feb 2022Cochlear implants, like other active implants, rely on precise and effective electrical stimulation of the target tissue but become encapsulated by different amounts of...
Cochlear implants, like other active implants, rely on precise and effective electrical stimulation of the target tissue but become encapsulated by different amounts of fibrous tissue. The current study aimed at the development of a dual drug release from a PLLA coating and from the bulk material to address short-term and long-lasting release of anti-inflammatory drugs. Inner-ear cytocompatibility of drugs was studied in vitro. A PLLA coating (containing diclofenac) of medical-grade silicone (containing 5% dexamethasone) was developed and release profiles were determined. The influence of different coating thicknesses (2.5, 5 and 10 µm) and loadings (10% and 20% diclofenac) on impedances of electrical contacts were measured with and without pulsatile electrical stimulation. Diclofenac can be applied to the inner ear at concentrations of or below 4 × 10 mol/L. Release of dexamethasone from the silicone is diminished by surface coating but not blocked. Addition of 20% diclofenac enhances the dexamethasone release again. All PLLA coatings serve as insulator. This can be overcome by using removable masking on the contacts during the coating process. Dual drug release with different kinetics can be realized by adding drug-loaded coatings to drug-loaded silicone arrays without compromising electrical stimulation.
Topics: Animals; Anti-Inflammatory Agents; Coated Materials, Biocompatible; Cochlear Implants; Dexamethasone; Diclofenac; Drug Delivery Systems; Drug Liberation; Rats; Rats, Sprague-Dawley
PubMed: 35209205
DOI: 10.3390/molecules27041417 -
The Science of the Total Environment Feb 2022Diclofenac is a pharmaceutical active compound frequently detected in wastewater and water bodies, and often reported to be persistent and difficult to biodegrade. While...
Diclofenac is a pharmaceutical active compound frequently detected in wastewater and water bodies, and often reported to be persistent and difficult to biodegrade. While many previous studies have focussed on assessing diclofenac biodegradation in nitrification and denitrification processes, this study focusses on diclofenac biodegradation in the enhanced biological phosphorus removal (EBPR) process, where the efficiency of this process for diclofenac biodegradation as well as the metabolites generated are not well understood. An enrichment of Accumulibacter polyphosphate accumulating organisms (PAOs) was operated in an SBR for over 300 d, and acclimatized to 20 μg/L of diclofenac, which is in a similar range to that observed in domestic wastewater influents. The diclofenac biotransformation was monitored in four periods of stable operation and linked to the microbial community and metabolic behaviour in each period. Nitrification was observed in two of the four periods despite the addition of a nitrification inhibitor, and these periods were positively correlated with increased diclofenac biodegradation. Interestingly, in two periods with excellent phosphorus removal (>99%) and no nitrification, different levels of diclofenac biotransformation were observed. Period 2, enriched in Accumulibacter Type II achieved more significant diclofenac biotransformation (3.4 μg/gX), while period 4, enriched in Accumulibacter Type I achieved lower diclofenac biotransformation (0.4 μg/gX). In total, 23 transformation products were identified, with lower toxicity than the parent compound, enabling the elucidation of multiple metabolic pathways for diclofenac biotransformation. This study showed that PAOs can contribute to diclofenac biotransformation, yielding less toxic transformation products, and can complement the biodegradation carried out by other organisms in activated sludge, particularly nitrifiers.
Topics: Bioreactors; Biotransformation; Diclofenac; Phosphorus; Sewage
PubMed: 34715209
DOI: 10.1016/j.scitotenv.2021.151232 -
The Pan African Medical Journal 2022Artemisia is one of the important alternative treatments for many diseases, as well as the prevention of the effect of oxidizing substances that cause damage to the...
INTRODUCTION
Artemisia is one of the important alternative treatments for many diseases, as well as the prevention of the effect of oxidizing substances that cause damage to the various organs of the body, including the liver and kidneys. The kidney and the liver are considered the body's most critical organs, and their functions in storage, metabolism, detoxification and elimination of medications, and their metabolic products make them target structures for "drug-induced" harm. The goal of this investigation was to see if Artemisia extract might protect hepatic and renal tissues from diclofenac-induced damage.
METHODS
a total of 40 adult Wistar rats were separated equally into four groups randomly. The rats of the control group got only distilled water orally without medicine or therapy, while those in the second group administrated 100mg/kg/day of Artemisia orally for one month. The third group received 10mg/kg/day of Diclofenac (DF) orally. The fourth group received 10mg/kg/day of DF and 100mg/kg day of Artemisia orally. After one month, kidney parameters (albumin, creatinine, and urea) and liver parameters (aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP)) were measured.
RESULTS
the results revealed increasing in the kidney (albumin, creatinine, and urea) parameters and liver parameters (AST, ALT, and ALP) in the group treated with diclofenac compared to the control group while they decreased significantly (p≤0.05) in diclofenac + Artemisia group comparing to diclofenac group.
CONCLUSION
we conclude from these results that Artemisia may have a role in reducing the toxic effect of diclofenac on kidney and liver by decreasing the liver enzymes and kidney criteria in the blood. The aim of the present study is to evaluate the role of Artemisia to reduce the toxic effect of diclofenac on liver and kidney.
Topics: Rats; Male; Animals; Diclofenac; Rats, Wistar; Artemisia; Creatinine; Plant Extracts; Liver; Kidney; Alkaline Phosphatase; Urea; Albumins
PubMed: 36942132
DOI: 10.11604/pamj.2022.43.192.36160 -
Andrologia Oct 2020The adverse effect of diclofenac administration on the male reproductive organ in both humans and rats has been reported. Selenium, a trace element vital in nutrition,...
The adverse effect of diclofenac administration on the male reproductive organ in both humans and rats has been reported. Selenium, a trace element vital in nutrition, plays a significant part in cellular redox homeostasis, including male reproduction. However, the impact of selenium on male reproductive toxicity associated with diclofenac administration is lacking in the literature. The current investigation assessed the modulatory effects of selenium on diclofenac-mediated reproductive toxicity in rats. Rats were treated for fourteen consecutive days, either with diclofenac (10 mg/kg) or co-treated with selenium (0.125 and 0.25 mg/kg) body weight. Sperm parameters, enzymes of testicular function, luteinizing, follicle-stimulating hormone and testosterone were assessed in addition to oxidative stress indices and histopathological changes. Selenium significantly alleviated diclofenac-induced decreases in sperm count and motility, testicular function enzymes and levels of luteinizing hormone and testosterone in serum. Moreover, selenium co-administration at 0.125 and 0.25 mg/kg inhibited the diclofenac-induced decrease of antioxidant enzyme activities and increased oxidative stress parameters-lipid peroxidation, reactive nitrogen and oxygen species-in epididymis and testes of rats. Selenium (0.25 mg/kg) alone ameliorated diclofenac-mediated histological injuries in exposed rats. Collectively, selenium enhanced testicular and epididymal function in diclofenac-treated rats by suppressing nitrosative and oxidative stress in rats.
Topics: Animals; Antioxidants; Diclofenac; Epididymis; Lipid Peroxidation; Male; Oxidative Stress; Rats; Rats, Wistar; Selenium; Spermatozoa; Testis; Testosterone
PubMed: 32510627
DOI: 10.1111/and.13669 -
Journal of Drug Targeting Sep 2022Effective and safe therapies to counteract persistent inflammation are necessary. We developed erythrocyte-derived liposomes (EDLs) with intrinsic anti-inflammatory...
Effective and safe therapies to counteract persistent inflammation are necessary. We developed erythrocyte-derived liposomes (EDLs) with intrinsic anti-inflammatory activity. The EDLs were prepared using lipids extracted from erythrocyte membranes, which are rich in omega-3 fatty acids with several health benefits. Diclofenac, a widely used anti-inflammatory drug, was incorporated into EDLs in relevant therapeutic concentrations. The EDLs were also functionalised with folic acid to allow their active targeting of M1 macrophages, which are key players in inflammatory processes. In the presence of lipopolysaccharide (LPS)-stimulated macrophages, empty EDLs and EDLs incorporating diclofenac were able to reduce the levels of important pro-inflammatory cytokines, namely interleukin-6 (IL-6; ≈85% and 77%, respectively) and tumour necrosis factor-alpha (TNF-α; ≈64% and 72%, respectively). Strikingly, cytocompatible concentrations of EDLs presented similar effects to dexamethasone, a potent anti-inflammatory drug, in reducing IL-6 and TNF-α concentrations, demonstrating the EDLs potential to be used as bioactive carriers in the treatment of inflammatory diseases.
Topics: Anti-Inflammatory Agents; Cytokines; Diclofenac; Erythrocytes; Humans; Inflammation; Interleukin-6; Liposomes; Tumor Necrosis Factor-alpha
PubMed: 35414285
DOI: 10.1080/1061186X.2022.2066107 -
Environmental Pollution (Barking, Essex... Jul 2022Studies in recent years have shown that significant amounts of diclofenac (DCF) and its metabolites are present in marine coastal waters. Their continuous flow into the...
Studies in recent years have shown that significant amounts of diclofenac (DCF) and its metabolites are present in marine coastal waters. Their continuous flow into the environment may be associated with numerous negative effects on both fauna and flora. Although more and more is known about the effects of pharmaceuticals on marine ecosystems, there are still many issues that have not received enough attention, but are essential for risk assessment, such as long term stability. Furthermore, interaction of pharmaceuticals with sediments, which are inhabited by rich microbial, meiofaunal and macrobenthic communities need investigation. Therefore, we undertook an analysis of the stability of DCF and its metabolite, 4-hydroxy diclofenac, in seawater and sediment collected from the brackish environment of Puck Bay. Our 29-day experiment was designed to gain a better understanding of the fate of these compounds under experimental conditions same as near the seafloor. Diclofenac concentration decreased by 31.5% and 20.4% in the tanks with sediment and autoclaved sediment, respectively during 29-day long experiment. In contrast, the concentration of 4-OH diclofenac decreased by 76.5% and 90.2% in sediment and autoclaved sediment, respectively. The concentration decrease of both compounds in the sediment tanks resulted from their sorption in the sediment and biodegradation. Obtained results show that marine sediments favour DCF and 4-OH DCF removal from the water column.
Topics: Diclofenac; Ecosystem; Geologic Sediments; Pharmaceutical Preparations; Seawater; Water Pollutants, Chemical
PubMed: 35381302
DOI: 10.1016/j.envpol.2022.119243