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The Journal of Dermatological Treatment Dec 2023Seborrheic keratoses (SKs) are benign epidermal neoplasms presenting as waxy, brown to black papules and plaques. Patients often seek removal for cosmetic reasons or...
Seborrheic keratoses (SKs) are benign epidermal neoplasms presenting as waxy, brown to black papules and plaques. Patients often seek removal for cosmetic reasons or irritation. The objective of this systematic review is to assess the efficacy and safety of topical treatments for SKs. Studies involving any topical medication indicated for SK removal were retrieved from Embase, Scopus, PubMed, and Cochrane. The final search was conducted on November 9, 2021, and 26 reports met inclusion criteria. A quality rating scheme was utilized to assess evidence quality. Heterogeneity of treatments and outcome measures precluded meta-analysis. Topical treatments that yielded a good-to-excellent response include hydrogen peroxide, Maxacalcitol 25 µg/g, BID Tazarotene 0.1% cream, 5% potassium dobesilate cream, 1% diclofenac sodium solution, urea-based solution, and 65% and 80% trichloroacetic acid. Local skin reactions were often mild and transient. Topical hydrogen peroxide showed the greatest evidence for clinical clearance of SKs, although there are no studies to our knowledge that directly compared hydrogen peroxide to current first-line treatments (e.g. cryotherapy or shave excision). The results of this review suggest viable and safe treatment of SK with topical therapies; however, there remains demand for topical treatments that reliably equate or exceed the efficacy of current first-line therapies.Key Points Are safe and efficacious topical treatments for seborrheic keratoses available? Topical treatments for seborrheic keratoses yield different responses and may be associated with local skin reactions. Topical hydrogen peroxide shows the greatest evidence for clinical clearance of seborrheic keratoses and may be a viable option for patients requesting noninvasive removal. No studies to our knowledge directly compare hydrogen peroxide to current first-line treatments. There remains demand for topical treatments that reliably equate or exceed the efficacy of current first-line therapies.
Topics: Humans; Administration, Topical; Cryotherapy; Hydrogen Peroxide; Keratosis, Seborrheic; Treatment Outcome
PubMed: 36215682
DOI: 10.1080/09546634.2022.2133532 -
Physiological Reports Sep 2023The aim of our study is to investigate the electrophysiological and anti-inflammatory effects of diclofenac potassium on epileptiform activity, which is the liquid form...
The aim of our study is to investigate the electrophysiological and anti-inflammatory effects of diclofenac potassium on epileptiform activity, which is the liquid form of diclofenac, and frequently used clinically for inflammatory process by inhibiting cyclooxygenase enzyme (COX). Wistar rats aged 2-4 months were divided into Epilepsy, Diazepam, Diclofenac potassium, and Diazepam+diclofenac potassium groups. Diazepam and diclofenac potassium were administered intraperitoneally 30 min after the epileptiform activity was created with penicillin injected intracortically under anesthesia. After the electrophysiological recording was taken in the cortex for 125 min, interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were evaluated by the ELISA in the serums. No change was observed between the groups in serum IL-1β, IL-6, and TNF-α values. It was observed that the co-administration of diclofenac potassium and diazepam at 51-55, 56-60, 61-65, 111-115, and 116-120 min was more effective in reducing spike amplitude than diclofenac potassium alone (p < 0.05). Single-dose diclofenac potassium did not have an anti-inflammatory effect in epileptiform activity but both diazepam and diclofenac potassium reduced the epileptiform activity.
Topics: Rats; Animals; Rats, Wistar; Diclofenac; Interleukin-6; Tumor Necrosis Factor-alpha; Cyclooxygenase 2; Diazepam; Anti-Inflammatory Agents
PubMed: 37688418
DOI: 10.14814/phy2.15800 -
Medicina (Kaunas, Lithuania) May 2024: Stem cell-based regeneration strategies have shown therapeutic efficacy in various fields of regenerative medicine. These include bone healing after bone augmentation,...
: Stem cell-based regeneration strategies have shown therapeutic efficacy in various fields of regenerative medicine. These include bone healing after bone augmentation, often complicated by pain, which is managed by using nonsteroidal anti-inflammatory drugs (NSAIDs). However, information is limited about how NSAIDs affect the therapeutic potential of stem cells. : We investigated the effects of ibuprofen and diclofenac on the characteristics, morphology, and immunophenotype of human mesenchymal stromal cells isolated from the dental pulp () and cultured in vitro, as well as their effects on the expression of angiogenic growth factors ( and ) and selected genes in apoptosis signalling pathways (, , , , and 2). : Ibuprofen and diclofenac significantly reduced the viability of DPSCs, while the expression of mesenchymal stem cell surface markers was unaffected. Both ibuprofen and diclofenac treatment significantly upregulated the expression of , while the expression of remained unchanged. Ibuprofen significantly altered the expression of several apoptosis-related genes, including the upregulation of and , with decreased expression. BAK, CASP3, CASP9, and BCL2 expressions were significantly increased in the diclofenac-treated DPSCs, while no difference was demonstrated in BAX expression. : Our results suggest that concomitant use of the NSAIDs ibuprofen or diclofenac with stem cell therapy may negatively impact cell viability and alter the expression of apoptosis-related genes, affecting the efficacy of stem cell therapy.
Topics: Humans; Dental Pulp; Diclofenac; Apoptosis; Ibuprofen; Cell Survival; Anti-Inflammatory Agents, Non-Steroidal; Stem Cells; Mesenchymal Stem Cells; Cells, Cultured
PubMed: 38792973
DOI: 10.3390/medicina60050787 -
Patient Preference and Adherence 2023Evaluate the efficacy of transdermal patches containing ketoprofen and diclofenac sodium compared to oral diclofenac tablets in reducing post-endodontic pain after...
Comparative Evaluation of Efficacy of Ketoprofen and Diclofenac Transdermal Patches with Oral Diclofenac Tablet on Postoperative Endodontic Pain- A Randomized Clinical Trial.
PURPOSE
Evaluate the efficacy of transdermal patches containing ketoprofen and diclofenac sodium compared to oral diclofenac tablets in reducing post-endodontic pain after single-visit root canal therapy for teeth with symptomatic irreversible pulpitis.
METHODS
A total of 78 eligible participants with symptomatic irreversible pulpitis and preoperative VAS scores of 4 or above were enrolled after obtaining ethical approval (SVIEC/ON/DENT/SRP/22064) and CTRI registration (CTRI/2022/07/044231). Exclusion criteria included pregnancy, lactation, fractured/cracked teeth, developmental anomalies, tooth pathology, or ongoing analgesic/NSAID use. After root canal treatment, participants were randomized into three groups using computer randomization. Groups A and B received transdermal patches with Ketoprofen and diclofenac sodium, respectively, applied to the right forearm for 24 hours, with an additional patch on the left forearm for the next day. Group C received four diclofenac sodium oral tablets, twice daily for two days. VAS scales were used to assess pain at 4, 8, 24, and 48 hours post-treatment. The VAS scores collected were tabulated and statistically analyzed using SPSS version 21 with (P < 0.05). Shapiro Wilk test and the Related Samples Friedman's Two-Way Analysis of Variance by Ranks were used for statistical evaluation.
RESULTS
Statistically significant reductions in mean postoperative pain scores were observed across all groups at all time points compared to preoperative scores. Notably, the Ketoprofen patch group exhibited superior performance compared to the diclofenac transdermal patch and oral diclofenac tablet groups at 48 hours, with statistical significance (p=0.047).
CONCLUSION
The present evidence substantiates the efficacy of transdermal patches containing diclofenac and ketoprofen in managing postoperative pain arising from symptomatic irreversible pulpitis in single-rooted teeth. By avoiding the use of oral NSAIDs, these patches provide effective pain relief while minimizing the risk of adverse effects, presenting a favorable option for patients.
PubMed: 37790865
DOI: 10.2147/PPA.S421371 -
British Journal of Cancer Aug 2023B-raf inhibitors (BRAFi) are effective for BRAF-mutated papillary (PTC) and anaplastic (ATC) thyroid carcinomas, although acquired resistance impairs tumour cells'...
BACKGROUND
B-raf inhibitors (BRAFi) are effective for BRAF-mutated papillary (PTC) and anaplastic (ATC) thyroid carcinomas, although acquired resistance impairs tumour cells' sensitivity and/or limits drug efficacy. Targeting metabolic vulnerabilities is emerging as powerful approach in cancer.
METHODS
In silico analyses identified metabolic gene signatures and Hif-1α as glycolysis regulator in PTC. BRAF-mutated PTC, ATC and control thyroid cell lines were exposed to HIF1A siRNAs or chemical/drug treatments (CoCl, EGF, HGF, BRAFi, MEKi and diclofenac). Genes/proteins expression, glucose uptake, lactate quantification and viability assays were used to investigate the metabolic vulnerability of BRAF-mutated cells.
RESULTS
A specific metabolic gene signature was identified as a hallmark of BRAF-mutated tumours, which display a glycolytic phenotype, characterised by enhanced glucose uptake, lactate efflux and increased expression of Hif-1α-modulated glycolytic genes. Indeed, Hif-1α stabilisation counteracts the inhibitory effects of BRAFi on these genes and on cell viability. Interestingly, targeting metabolic routes with BRAFi and diclofenac combination we could restrain the glycolytic phenotype and synergistically reduce tumour cells' viability.
CONCLUSION
The identification of a metabolic vulnerability of BRAF-mutated carcinomas and the capacity BRAFi and diclofenac combination to target metabolism open new therapeutic perspectives in maximising drug efficacy and reducing the onset of secondary resistance and drug-related toxicity.
Topics: Humans; Diclofenac; Proto-Oncogene Proteins B-raf; Mutation; Protein Kinase Inhibitors; Thyroid Neoplasms; Glycolysis; Phenotype; Glucose; Cell Line, Tumor
PubMed: 37198319
DOI: 10.1038/s41416-023-02282-2 -
Biomedicines Dec 2023Fibromyalgia (FM) is a chronic pain condition characterized by widespread musculoskeletal pain and other frequent symptoms such as fatigue, sleep disturbance, cognitive... (Review)
Review
Fibromyalgia (FM) is a chronic pain condition characterized by widespread musculoskeletal pain and other frequent symptoms such as fatigue, sleep disturbance, cognitive impairment, and mood disorder. Based on the view that intermittent stress would be the most probable etiology for FM, intermittent cold- and intermittent psychological stress-induced generalized pain (ICGP and IPGP) models in mice have been developed and validated as FM-like pain models in terms of the patho-physiological and pharmacotherapeutic features that are shared with clinical versions. Both models show long-lasting and generalized pain and female-predominant sex differences after gonadectomy. Like many other neuropathic pain models, ICGP and IPGP were abolished in lysophosphatidic acid receptor 1 (LPAR) knock-out mice or by LPAR antagonist treatments, although deciding the clinical importance of this mechanism depends on waiting for the development of a clinically available LPAR antagonist. On the other hand, the nonsteroidal anti-inflammatory drug diclofenac with morphine did not suppress hyperalgesia in these models, and this is consistent with the clinical findings. Pharmacological studies suggest that the lack of morphine analgesia is associated with opioid tolerance upon the stress-induced release of endorphins and subsequent counterbalance through anti-opioid NMDA receptor mechanisms. Regarding pharmacotherapy, hyperalgesia in both models was suppressed by pregabalin and duloxetine, which have been approved for FM treatment in clinic. Notably, repeated treatments with mirtazapine, an α2 adrenergic receptor antagonist-type antidepressant, and donepezil, a drug for treating Alzheimer's disease, showed potent therapeutic actions in these models. However, the pharmacotherapeutic treatment should be carried out 3 months after stress, which is stated in the FM guideline, and many preclinical studies, such as those analyzing molecular and cellular mechanisms, as well as additional evidence using different animal models, are required. Thus, the ICGP and IPGP models have the potential to help discover and characterize new therapeutic medicines that might be used for the radical treatment of FM, although there are several limitations to be overcome.
PubMed: 38255163
DOI: 10.3390/biomedicines12010056 -
Photodiagnosis and Photodynamic Therapy Sep 2023Photodynamic therapy (PDT) is approved for treatment of actinic keratoses (AKs) and field-cancerisation. Pretreatment with pharmacological compounds holds potential to... (Review)
Review
BACKGROUND
Photodynamic therapy (PDT) is approved for treatment of actinic keratoses (AKs) and field-cancerisation. Pretreatment with pharmacological compounds holds potential to improve PDT efficacy, through direct interaction with PpIX formation or through an independent response, both of which may improve PDT treatment.
OBJECTIVE
To present the currently available clinical evidence of pharmacological pretreatments prior to PDT and to associate potential clinical benefits with the pharmacological mechanisms of action of the individual compounds.
METHODS
A comprehensive search on the Embase, MEDLINE, and Web of Science databases was performed.
RESULTS
In total, 16 studies investigated 6 pretreatment compounds: 5-fluorouracil (5-FU), diclofenac, retinoids, salicylic acid, urea, and vitamin D. Two of these, 5-FU and vitamin D, robustly increased the efficacy of PDT across multiple studies, illustrated by mean increases in clearance rates of 21.88% and 12.4%, respectively. Regarding their mechanisms, 5-FU and vitamin D both increased PpIX accumulation, while 5-FU also induced a separate anticarcinogenic response. Pretreatment with diclofenac for four weeks improved the clearance rate in one study (24.9%), administration of retinoids had a significant effect in one of two studies (16.25%), while salicylic acid and urea did not lead to improved PDT efficacy. Diclofenac and retinoids demonstrated independent cytotoxic responses, whereas salicylic acid and urea acted as penetration enhancers to increase PpIX formation.
CONCLUSION
5-FU and vitamin D are well-tested, promising candidates for pharmacological pretreatment prior to PDT. Both compounds affect the haem biosynthesis, providing a target for potential pretreatment candidates.
KEY WORDS
Photodynamic Therapy, Actinic Keratosis,Pre-tretment,Review,enhancement.
Topics: Humans; Keratosis, Actinic; Photosensitizing Agents; Aminolevulinic Acid; Photochemotherapy; Diclofenac; Salicylic Acid; Fluorouracil; Retinoids; Vitamin D; Urea; Treatment Outcome
PubMed: 37429460
DOI: 10.1016/j.pdpdt.2023.103703 -
CA: a Cancer Journal For Clinicians 2024Pain is one of the most burdensome symptoms in people with cancer, and opioid analgesics are considered the mainstay of cancer pain management. For this review, the... (Review)
Review
Pain is one of the most burdensome symptoms in people with cancer, and opioid analgesics are considered the mainstay of cancer pain management. For this review, the authors evaluated the efficacy and toxicities of opioid analgesics compared with placebo, other opioids, nonopioid analgesics, and nonpharmacologic treatments for background cancer pain (continuous and relatively constant pain present at rest), and breakthrough cancer pain (transient exacerbation of pain despite stable and adequately controlled background pain). They found a paucity of placebo-controlled trials for background cancer pain, although tapentadol or codeine may be more efficacious than placebo (moderate-certainty to low-certainty evidence). Nonsteroidal anti-inflammatory drugs including aspirin, piroxicam, diclofenac, ketorolac, and the antidepressant medicine imipramine, may be at least as efficacious as opioids for moderate-to-severe background cancer pain. For breakthrough cancer pain, oral transmucosal, buccal, sublingual, or intranasal fentanyl preparations were identified as more efficacious than placebo but were more commonly associated with toxicities, including constipation and nausea. Despite being recommended worldwide for the treatment of cancer pain, morphine was generally not superior to other opioids, nor did it have a more favorable toxicity profile. The interpretation of study results, however, was complicated by the heterogeneity in the study populations evaluated. Given the limited quality and quantity of research, there is a need to reappraise the clinical utility of opioids in people with cancer pain, particularly those who are not at the end of life, and to further explore the effects of opioids on immune system function and quality of life in these individuals.
Topics: Humans; Analgesics, Opioid; Cancer Pain; Anti-Inflammatory Agents, Non-Steroidal; Nociceptive Pain; Neoplasms; Pain Management
PubMed: 38108561
DOI: 10.3322/caac.21823 -
Veterinary World Sep 2023Ruiz and Pav. (also known as "Pájaro bobo") is known for its medicinal properties, including antiulcer, antiasthmatic, leishmanicidal, antipyretic, antispasmodic,...
BACKGROUND AND AIM
Ruiz and Pav. (also known as "Pájaro bobo") is known for its medicinal properties, including antiulcer, antiasthmatic, leishmanicidal, antipyretic, antispasmodic, diuretic, anti-inflammatory, analgesic, and hepatoprotective effects. Therefore, we aimed to evaluate its hepatoprotective and nephroprotective effects using a rat model of diclofenac-induced toxicity.
MATERIALS AND METHODS
We administered three different doses of the methanolic extract of (100, 200, and 400 mg/kg/day orally) and compared them with the commercial medicine silymarin (100 mg/kg orally). The rats received the extracts for 5 days, and on days 3 and 4, 1 h after receiving the extracts, diclofenac was administered intraperitoneally at a dose of 50 mg/kg. The animals were euthanized 48 h after the last diclofenac injection, and blood samples were obtained to measure biochemical parameters related to liver and kidney function, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, cholesterol, triglycerides, creatinine, and urea. Kidney and liver tissues were preserved in 10% formaldehyde and sent for histopathological analysis.
RESULTS
The results show that has hepatoprotective and nephroprotective effects. These effects are verified by the lower blood levels of ALT, AST, urea, and creatinine compared to the diclofenac group, which exhibited elevated biochemical parameters. In addition, histopathological analysis showed that the groups that received did not display necrosis or infiltration, which were observed in the diclofenac group.
CONCLUSION
The methanolic extract of has hepatoprotective and nephroprotective effects, with the highest protective activity observed at a dose of 400 mg/kg/day.
PubMed: 37859960
DOI: 10.14202/vetworld.2023.1933-1939 -
Environmental Science and Pollution... Jul 2023Bioremediation of pharmaceuticals has gained large research efforts, but there is still a need to improve the performance of bioremediation systems by selecting...
Bioremediation of pharmaceuticals has gained large research efforts, but there is still a need to improve the performance of bioremediation systems by selecting effective organisms. In this study, we characterized the capability to remove clarithromycin (CLA) and diclofenac (DCF) by the bacterium Streptomyces rochei, and the fungi Phanerochaete chrysosporium and Trametes versicolor. The macrolide antibiotic CLA and the non-steroid anti-inflammatory DCF were selected because these are two of the most frequently detected drugs in water bodies. Growth and content of the PhCs and a DCF metabolite (MET) by the energy crop Arundo donax L. were also evaluated under hydroponic conditions. The removal rate (RR) by S. rochei increased from 24 to 40% at 10 and 100 µg CLA L, respectively, averaged over incubation times. At 144 h, the RR by P. chrysosporium was 84%, while by T. versicolor was 70 and 45% at 10 and 100 CLA µg L. The RR by S. rochei did not exceed 30% at 1 mg DCF L and reached 60% at 10 mg DCF L, whereas approached 95% and 63% by P. chrysosporium and T. versicolor, respectively, at both doses. Root biomass and length of A. donax were strongly affected at 100 µg CLA L. CLA concentration in roots and shoots increased with the increase of the dose and translocation factor (TF) was about 1. DCF severely affected both shoot fresh weight and root length at the highest dose and concentration in roots and shoots increased with the increase of the dose. DCF concentrations were 16-19 times higher in roots than in shoots, and TF was about 0.1. MET was detected only in roots and its proportion over the parent compound decreased with the increase of the DCF dose. This study highlights the potential contribution of A. donax and the tested microbial inoculants for improving the effectiveness of bioremediation systems for CLA and DCF removal.
Topics: Diclofenac; Wastewater; Clarithromycin; Biodegradation, Environmental; Trametes; Poaceae
PubMed: 37249765
DOI: 10.1007/s11356-023-27660-4