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Electroporation technique for joint pain - Pilot feasibility study on TMD patients.
Tartaglia, GM, Gizdulich, A, Farronato, M, Gupta, RJ, Connelly, ST
Clinical and experimental dental research. 2020;(6):642-649
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Abstract
OBJECTIVE(S): It is well appreciated that traditional analgesic delivery routes used to treat pain associated with temporomandibular disorder (TMD) often have harmful unintended side effects as a consequence of systemic distribution. Further, localized delivery of analgesic medication via intra-articular injections involves a different set of issues limiting their clinical viability. As an option, transdermal analgesic delivery provides for prolonged pain relief and flexibility in dose administration, while limiting systemic exposure and minimizing adverse events. Incorporation of a novel electroporation technique may further increase transdermal drug penetration into synovial tissue/fluid and enhance pain reduction. The present feasibility study compares the effectiveness of an electroporation-enhanced transdermal application of diclofenac sodium to a conventional intra-articular injection of triamcinolone acetonide suspension (corticosteroids) to treat patients with TMD associated pain. METHODS Pre- and post-treatment maximal incisal mouth opening (MIO), pain visual analog scale (VAS) and surface electromyography (EMG) of 22 patients treated with electroporation-enhanced diclofenac and 37 patients treated with corticosteroids injections were collected and analyzed. RESULTS In general, patients treated with electroporation exhibited better results in terms of pain improvement (corrected p-value = .01) compared to the standard treatment, but both methods were similarly effective for improvement of MIO (corrected p-value = .71) and improvement of all EMG indices (corrected p-values ≥ .05). CONCLUSION The enhancing effect of electroporation in transdermal delivery of diclofenac sodium was demonstrated by decreased pain, increase MIO and EMG improvement to normal values. Its analgesic and inflammatory results are comparable with standard treatment offered by corticosteroids.
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Effects of curcumin on mitochondria in neurodegenerative diseases.
Bagheri, H, Ghasemi, F, Barreto, GE, Rafiee, R, Sathyapalan, T, Sahebkar, A
BioFactors (Oxford, England). 2020;(1):5-20
Abstract
Neurodegenerative diseases (NDs) result from progressive deterioration of selectively susceptible neuron populations in different central nervous system (CNS) regions. NDs are classified in accordance with the primary clinical manifestations (e.g., parkinsonism, dementia, or motor neuron disease), the anatomic basis of neurodegeneration (e.g., frontotemporal degenerations, extrapyramidal disorders, or spinocerebellar degenerations), and fundamental molecular abnormalities (e.g., mutations, mitochondrial dysfunction, and its related molecular alterations). NDs include the Alzheimer disease and Parkinson disease, among others. There is a growing evidence that mitochondrial dysfunction and its related mutations in the form of oxidative/nitrosative stress and neurotoxic compounds play major roles in the pathogenesis of various NDs. Curcumin, a polyphenol and nontoxic compound, obtained from turmeric, has been shown to have a therapeutic beneficial effect in various disorders especially on the CNS cells. It has been shown that curcumin has considerable neuro- and mitochondria-protective properties against broad-spectrum neurotoxic compounds and diseases/injury-associating NDs. In this article, we have reviewed the various effects of curcumin on mitochondrial dysfunction in NDs.
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Comparison of intradermal mesotherapy with systemic therapy in the treatment of low back pain: A prospective randomized study.
Akbas, I, Kocak, AO, Kocak, MB, Cakir, Z
The American journal of emergency medicine. 2020;(7):1431-1435
Abstract
INTRODUCTION Musculoskeletal pain such as low back pain (LBP) are routinely encountered in the ED and contribute to ED overcrowding. The aim of our study was to compare the efficiency of mesotherapy with systemic therapy in pain control in patients with lumbar disk herniation. METHODS We conducted this prospective parallel randomized controlled trial with the patients admitted to the emergency department with low back pain related to herniated lumbar disk. Mesotherapy was performed to one group, while intravenous dexketoprofen was administered to the control group. Changes in pain intensity at 15th minute, 30th minute, 60th minute and 24th hours after treatment using Visual Analogue Scale (VAS), need to use analgesic drug within 24 h after treatment, and adverse effect of the treatment methods were compared between groups. RESULTS The decreases in pain intensity were statistically significantly higher in mesotherapy group for all time intervals. The need to use analgesics was statistically significantly three fold higher in the systemic therapy group. There was no statistically significant difference in having any adverse effect between study groups during one-week follow-up period. CONCLUSIONS Changes in medical practices, from the systemic administration of NSAIDs to the minimally invasive techniques such as mesotherapy with potent efficacy and minimal side effects, may enhance the ability of EDs to meet the waiting time targets and improve patient's satisfaction.
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Topical Ketoprofen Versus Placebo in Children Presenting With Ankle Sprain to the Emergency Department: A Randomized Controlled Study.
Serinken, M, Eken, C, Tünay, K, Gölcük, Y
Pediatric emergency care. 2020;(8):e447-e450
Abstract
OBJECTIVE Despite the favorable data concerning topical agents use in outpatient clinics, they are not commonly in emergency departments (EDs). The present study aimed to compare the effect of 2.5% topical ketoprofen (gel form) to placebo in children presenting with ankle sprain to the ED. STUDY DESIGN Children between 7 and 18 years old presenting with ankle sprain composed the study population. Study patients were randomized into 2 study arms: 2.5% ketoprofen gel and placebo administered in a 5-cm area locally. Pain improvements at 15 and 30 minutes were measured by visual analog scale. RESULTS Median pain reductions at 15 minutes for ketoprofen and placebo groups were 27.5 (16-39) and 5 (4-10), respectively. Median changes in pain intensity at 30 minutes for ketoprofen and placebo gel groups were 48 (43-52) and 9 (6-16), respectively. When compared 2 arms for the pain improvement at 15 and 30 minutes, the differences between 2 study drugs were 20 (13-28) and 35 (29-41), respectively. There were 7 (12.7%) rescue drug needs in the placebo group and 1 (1.7%) in the ketoprofen group (difference, 10.9%; 95% confidence interval, -6% to 7%; P = 0.83). There were no adverse effects in either group. CONCLUSIONS Ketoprofen gel is superior to placebo in ceasing pain in children presenting with ankle sprain to the ED with a high safety profile.
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Influence of Microbiota on NSAID Enteropathy: A Systematic Review of Current Knowledge and the Role of Probiotics.
Rekatsina, M, Paladini, A, Cifone, MG, Lombardi, F, Pergolizzi, JV, Varrassi, G
Advances in therapy. 2020;(5):1933-1945
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Abstract
Microbiota are increasingly studied, providing more precise information on their important role in physiologic processes. They also influence some pathologic processes, such as NSAID-induced enteropathy. This side effect is much more diffuse than it has been described in the past. It derives mainly from the local action of the medicines and is caused by the local binding of gram-negative bacterial lipopolysaccharides and infiltration of neutrophils into the intestinal mucosa. The initial interest in the interaction between these damages and microbiota is very old, but new and interesting data are available. This review aims to focus on recent studies on NSAID-induced enteropathy, an often-underestimated medical condition, and on the influence of microbiota on this condition. Apart from the broadly investigated use of antibiotics and other mucosal protective solutions, this systematic review focuses mostly on the use of probiotics, which directly influence intestinal microflora. Other important factors influencing NSAID-induced enteropathy, such as sex, advanced age, infection and use of proton pump inhibitors, are also discussed.
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Photobiomodulation as oedema adjuvant in post-orthognathic surgery patients: A randomized clinical trial.
Domínguez Camacho, A, Velásquez, SA, Benjumea Marulanda, NJ, Moreno, M
International orthodontics. 2020;(1):69-78
Abstract
OBJECTIVE Photobiomodulation therapy (PBMT) has been used in multiple applications in general medicine as powerful anti-inflammatory, analgesic and reducing oedema in different parts of the body. The aim of this study is to compare the effect on post-surgical oedema after mandibular orthognathic surgery, between two different laser power densities and oral medication with non-steroidal anti-inflammatory. MATERIALS AND METHODS In a randomized clinical trial, on 60 patients who were subject to mandibular orthognathic surgery were divided into three groups. All groups received sodium naproxen 250mg every 8hours for 6days. Two groups were irradiated with two different laser application protocols and the other was a control group. In G1 group the irradiation parameters three times per week for two weeks were: 940nm, in continuous mode, 2.5W, 120s, 85.71J/cm2, 0.89W/cm2, over the right and left side with a distance from the skin surface of 1mm with the whitening handpiece (spot size of 2.8cm2). In G2, the irradiation parameters three times a week for two weeks were: 940nm, in continuous mode, 4.1W, 120s, 68.33J/cm2, 0.58W/cm2 over the right and left side with a distance from the skin surface of 15mm, with the deep tissue handpiece (spot size of 7.1cm2). In all the groups, millimetric facial measurements were taken from tragus to lateral commissure, and from lateral commissure to gonion in both sides. RESULTS All differences between T1 and T6 were significant for the three groups, (paired T, P<0.05). The differences between the groups were generally not significant (P>0.05) except for commissure - right and left gonion when compared G1 vs CG (P<0.05) and G2 vs CG (P<0.05). Initial changes (T1-T2) between groups were significantly different except for the measurement from commissure to right tragus G1 vs CG (P=0.411) and from commissure to left tragus G2 vs CG (P=0.94). The faster resolution of the oedema occurred in G2 group. PTBM with an energy density of 68.33J/cm2 was the most effective adjuvant to oral medication with non-steroidal anti-inflammatory, to decrease post-surgical oedema after mandibular orthognathic surgery.
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Efficacy and safety of combination of curcuminoid complex and diclofenac versus diclofenac in knee osteoarthritis: A randomized trial.
Shep, D, Khanwelkar, C, Gade, P, Karad, S
Medicine. 2020;(16):e19723
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Abstract
BACKGROUND To compare the efficacy and safety of combination of curcuminoid complex and diclofenac vs diclofenac alone in the treatment of knee osteoarthritis (OA). METHODS In this randomized trial, 140 patients of knee OA received either curcuminoid complex 500 mg (BCM-95) with diclofenac 50 mg 2 times daily or diclofenac 50 mg alone 2 times daily for 28 days. Patients were assessed at baseline, day 14 and day 28. Primary efficacy measures were Knee injury and OA outcome score (KOOS) subscale at day 14 and day 28. Anti-ulcer effect and patient-physician's global assessment of therapy at day 28 were included as secondary endpoints. Safety after treatment was evaluated by recording adverse events and laboratory investigations. RESULTS Both treatment groups showed improvement in primary endpoints at each evaluation visit. Patients receiving curcuminoid complex plus diclofenac showed significantly superior improvement in KOOS subscales, viz. pain and quality of life at each study visit (P < .001) when compared to diclofenac. Less number of patients required rescue analgesics in curcuminoid complex plus diclofenac group (3%) compared to diclofenac group (17%). The number of patients who required histamine 2 (H2) blockers was significantly less in curcuminoid complex plus diclofenac group compared to diclofenac group (6% vs 28%, respectively; P < .001). Adverse effects were significantly less in curcuminoid complex plus diclofenac group (13% vs 38% in diclofenac group; P < .001). Patient's and physician's global assessment of therapy favored curcuminoid complex plus diclofenac than diclofenac. CONCLUSION Combination of curcuminoid complex and diclofenac showed a greater improvement in pain and functional capacity with better tolerability and could be a better alternative treatment option in symptomatic management of knee OA. TRIAL REGISTRATION ISRCTN, ISRCTN10074826.
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Gelatin nanoparticles for NSAID systemic administration: Quality by design and artificial neural networks implementation.
Koletti, AE, Tsarouchi, E, Kapourani, A, Kontogiannopoulos, KN, Assimopoulou, AN, Barmpalexis, P
International journal of pharmaceutics. 2020;:119118
Abstract
The present study evaluates the preparation of systemic administrated NSAID gelatin nanoparticles with the aid of quality by design and artificial neural networks (ANNs). Specifically, two different preparation techniques (i.e. nanoprecipitation and two-step desolvation) were implemented for the formulation of diclofenac sodium (DLC) gelatin nanoparticles (GNs). Preliminary screening experiments showed that in the case of nanoprecipitation the best compromise (in terms of achieving both small particle size and high encapsulation efficiency) was the use of poloxamer 407 (as stabilizer) and acetone (as non-solvent), while in the case of two-step desolvation significant effect had the use of acetone, gelatin type and bloom number (type B with bloom 150 was selected for further evaluation). Implementation of a central composite experimental design (CCD), showed that in the case of nanoprecipitation the optimum formulation can be achieved at high poloxamer, high gelatin and moderate to high glutaraldehyde (GTA used for crosslinking) concentrations, while in the case of two-step desolvation high gelatin and GTA concentrations are needed. Artificial neural networks (ANN) implementation showed significantly improved prediction ability compared to MLR, while verification experiments showed good agreement between the ANN predicted and the experimentally obtained results. SEM analysis of the optimum suggested formulations showed nanoparticles with smooth surface, while powder X-ray diffraction (XRD) analysis showed the formation of amorphously dispersed systems, and Fourier transform infrared spectroscopy (FTIR) revealed the presence of molecular interactions irrespectively of the preparation method followed. A slightly faster release profile was observed in the case of nanoprecipitation based GNs, while all formulations followed biphasic release profile.
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Incidence of cystoid macular edema following routine cataract surgery using NSAIDs alone or with corticosteroids.
Walter, KA, Lee, RY, Chen, K, Komanski, C
Arquivos brasileiros de oftalmologia. 2020;(1):55-61
Abstract
PURPOSE To evaluate the rate of cystoid macular edema development among cataract surgery patients on four different therapeutic regimens. METHODS The present study is a retrospective analysis of 5,380 eyes following uncomplicated phacoemulsification at Wake Forest University. The study period went from July 2007 to December 2012. Patients received one of four regimens, as follows: postoperative generic ketorolac 0.4% and prednisolone 1%, postoperative name-brand ketorolac 0.45% and prednisolone 1%, postoperative bromfenac 0.09% and prednisolone 1%, preoperative and postoperative bromfenac 0.09% alone. A statistical analysis was performed to assess the differences in rate of cystoid macular edema development among the four different therapeutic regimens. The diagnosis of cystoid macular edema required worsening of vision and evidence of increased macular thickness on optical coherence tomography. RESULTS The overall rate of cystoid macular edema was 0.82%. Treatment by postoperative generic ketorolac 0.45% and prednisolone 1% demonstrated the highest rate of cystoid macular edema development (2.20% of the cases). Postoperative name-brand ketorolac 0.45% and prednisolone 1% exhibited intermediate rates of cystoid macular edema development (0.90% of the cases). Postoperative administration of bromfenac 0.09% and prednisolone 1% exhibited intermediate rates of cystoid macular edema development (0.44% of the cases). Preoperative and postoperative bromfenac 0.09% alone resulted in the lowest rate of cystoid macular edema development (0.09% of the cases). The rate of cystoid macular edema was significantly lower when bromfenac was used alone vs. either regimen where ketorolac and prednisolone were used (OR 0.043, 95% CI 0.002 to 0.312; p<0.001). CONCLUSIONS Post-cataract surgery cystoid macular edema developed less frequently following topical non-steroidal anti-inflammatory drugs regimen compared to the other therapies evaluated. Bromfenac, without corticosteroids, achieved lower rates of cystoid macular edema vs. various combinations of non-ste-roidal anti-inflammatory drugs with corticosteroids.
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[The chemoreactomic analysis of the central mechanisms of action of non-steroidal anti-inflammatory drugs].
Gromova, OA, Torshin, IY, Putilina, MV, Stakhovskaia, LV, Rudakov, KV
Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova. 2020;(1):70-77
Abstract
AIM: To perform a chemoreactome modeling of the pharmacological central effects of 4 non-steroidal anti-inflammatory drugs (NSAIDs): dexketoprofen, ketoprofen, aceclofenac, lornoxicam. MATERIAL AND METHODS An analysis of the pharmacological spectrum of the central action of dexketoprofen, ketoprofen, aceclofenac and lornoxicam was based on the chemoinformatic approach, which compared drug-likeness properties with public and commercial software. RESULTS The effectiveness of NSAIDs is related to the inhibition of cannabinoid receptors CB-1, the vanilloid receptor TRPV1, NMDA and AMPA receptors and of the GABA reuptake transporter, with dexketoprofen being the most effective inhibitor. The safety of the central effects of NSAID is due to weak interactions of the NSAIDs studied with opioid, adrenergic, serotonin and dopamine receptors. Chemoreactome modeling made it possible to compare the particulars of the effects of the studied NSAIDs on experimental pain and cramps. CONCLUSION Inhibition of CB-1, TRPV1, NMDA, AMPA, GABA transporter by the NSAID molecules corresponds to a decrease in the intensity of nociceptive signals. A weak intervention of the studied NSAIDs in opioid, adrenergic, serotonin and dopaminergic neurotransmission corresponds to a decrease in the central side-effects of NSAIDs and to a lessened antagonism of these NSAIDs towards exogenous and endogenous opioids.