Opuntia monacantha: Validation of the anti-inflammatory and anti-arthritic activity of its polyphenolic rich extract in silico and in vivo via assessment of pro- and anti-inflammatory cytokines.

ETHNOPHARMACOLOGICAL RELEVANCE: Opuntia monacantha belongs to the cactus family Cactaceae and is also known by cochineal prickly pear, Barbary fig or drooping prickly pear. It was traditionally used to treat pain and inflammation. O. monacantha cladodes showed pharmacological effects such as antioxidant potential owing to the presence of certain polysaccharides, flavonoids, and phenols. AIM OF THE STUDY: This research aimed to evaluate the anti-inflammatory as well as the anti-arthritic potential of ethanol extract of Opuntia monacantha (E-OM). MATERIALS AND METHODS: In vivo edema in rat paw was triggered by carrageenan and used to evaluate anti-inflammatory activity, while induction of arthritis by Complete Freund's Adjuvant (CFA) rat model was done to measure anti-arthritic potential. In silico studies of the previously High performance liquid chromatography (HPLC) characterized metabolites of ethanol extract was performed by using Discovery Studio 4.5 (Accelrys Inc., San Diego, CA, USA) within active pocket of glutaminase 1 (GLS1) (PDB code: 3VP1; 2.30 Å). RESULTS: EOM, particularly at 750 mg/kg, caused a reduction in the paw edema significantly and decreased arthritic score by 80.58% compared to the diseased group. It revealed significant results when histopathology of ankle joint was examined at 28th day as it reduced inflammation by 18.06%, bone erosion by 15.50%, and pannus formation by 24.65% with respect to the diseased group. It restored the altered blood parameters by 7.56%, 18.47%, and 3.37% for hemoglobin (Hb), white blood count (WBC), and platelets, respectively. It also reduced rheumatoid factor RF by 13.70% with concomitant amelioration in catalase (CAT) and superoxide dismutase (SOD) levels by 19%, and 34.16%, respectively, in comparison to the diseased group. It notably decreased mRNA expression levels of COX-2, IL-6, TNF-α, IL-1, NF-κß and augmented the levels of IL-4 and IL-10 in real time PCR with respect to the diseased group and piroxicam. HPLC analysis previously performed showed that phenolic acids and flavonoids are present in E-OM. Molecular docking studies displayed pronounced inhibitory potential of these compounds towards glutaminase 1 (GLS1), approaching and even exceeding piroxicam. CONCLUSIONS: Thus, Opuntia monacantha could be a promising agent to manage inflammation and arthritis and could be incorporated into pharmaceuticals.

Quantum Sensing for Real-Time Monitoring of Drug Efficacy in Synovial Fluid from Arthritis Patients.

Diamond-based T1 relaxometry is a new technique that allows nanoscale magnetic resonance measurements. Here we present its first application in patient samples. More specifically, we demonstrate that relaxometry can determine the free radical load in samples from arthritis patients. We found that we can clearly differentiate between osteoarthritis and rheumatoid arthritis patients in both the synovial fluid itself and cells derived from it. Furthermore, we tested how synovial fluid and its cells respond to piroxicam, a common nonsteroidal anti-inflammatory drug (NSAID). It is known that this drug leads to a reduction in reactive oxygen species production in fibroblast-like synoviocytes (FLS). Here, we investigated the formation of free radicals specifically. While FLS from osteoarthritis patients showed a drastic decrease in the free radical load, cells from rheumatoid arthritis retained a similar radical load after treatment. This offers a possible explanation for why piroxicam is more beneficial for patients with osteoarthritis than those with rheumatoid arthritis.

Comparative study of piroxicam and nitroglycerin on prostaglandin-modulated blood and electrolyte indices during di-estrous in female Wistar Rats.

OBJECTIVE: Endogenous prostaglandins are involved in hemostasis, renal excretion of electrolytes, and implicated in dysmenorrhea. Piroxicam and Nitroglycerin are common drugs used in treating dysmenorrhea by inhibiting the cyclooxygenase pathway involved in prostaglandin production. However, studies comparing the effects of these drugs on prostaglandin-modulated hemostasis and renal function are lacking. METHODS: Fifteen female rats (120-160g) were divided into 3 groups (20 per group), namely Control (distilled water, 0.3 mL), Piroxicam treated (3mg/kg) and Nitroglycerin treated (1 mg/kg). Di-estrous phase was confirmed in animals in each group using the Pipette smear method. Treatment was administered for 4 days covering the estrous cycle. Bleeding and clotting time were assessed and blood concentrations of sodium, potassium, urea and platelet counts were evaluated in all phases. Data were analyzed using one-way ANOVA and Newman-Keuls post-hoc test. Statistical significance was considered at p<0.0. RESULTS: The nitroglycerin-treated group showed significant increases in blood potassium during di-estrous while the piroxicam-treated group showed significant increases in blood potassium, urea and clotting time with a significant decrease in sodium levels during di-estrous compared to controls. Results obtained in other phases were not significant compared to controls. CONCLUSIONS: The study showed that Nitroglycerin produces minimum alteration of blood and electrolyte indices compared to piroxicam during di-estrous.

Analgesic Effect of Topical Piroxicam vs Phytotherapy Gel in the Treatment of Acute Soft Tissue Injuries: A Randomized Controlled Noninferiority Study.

OBJECTIVE: The study compared the efficacy and tolerability of piroxicam gel and a new topical combination of medicinal plant products (Soulagel®; Belpharma Tunisia) to treat pain caused by soft tissue injuries. METHODS: Patients (n = 1,525) were assigned to receive piroxicam gel or Soulagel. Efficacy assessments included a change of at least 50% in the pain-on-movement visual numeric scale rating from emergency department discharge (baseline) to day 7 final assessment, as well as the time required to reach pain resolution criteria, the need for rescue analgesia, patients' satisfaction, and the rate of adverse effects. RESULTS: At day 7, 1,216 patients (79.7%) achieved at least 50% reduction in visual numeric scale rating from baseline: 623 patients (82.4%) in the Soulagel group vs 593 patients (77.1%) in the piroxicam group (P = 0.01). Time to decrease pain on movement by 50% was significantly higher with piroxicam gel than with Soulagel (34 ± 1 vs 33 ± 1 days, respectively; P = 0.54). At day 7, 96.4% of patients in the Soulagel group declared being "very satisfied" to "satisfied," vs 68% in the piroxicam group (P < 0.001). There were no major adverse events in either group. CONCLUSIONS: Soulagel is not inferior to piroxicam gel for managing pain related to a soft tissue injuries. Further studies will help ascertain whether this new gel offers an alternative treatment option for this common emergency department condition.

Comparison of Preoperative Analgesics on the Efficacy of Inferior Alveolar Nerve Block with Patients Having Symptomatic Irreversible Pulpitis: A Double-Blinded, Randomized Controlled Trial.

OBJECTIVE: The objective of this study was to evaluate the effectiveness of preoperative analgesics on inferior alveolar nerve blocks (IANB) during root canal treatment in patients with symptomatic irreversible pulpitis of the mandibular molars. METHODS: This study was a randomized, double-blinded, superiority trial with a parallel study design. A total of 120 subjects with symptomatic irreversible pulpitis were randomly assigned to one of four groups: group A (con- trol, Vitamin E, Evion 400 mg), group B (Diclofenac sodium, Voltral SR100 100 mg), group C (Piroxicam, Feldene 20 mg), and group D (Tramadol, Tramal 50 mg). The patients recorded preoperative pain levels, and after admin- istration of local anaesthesia intraoperative pain levels using the Heft-Parker visual analogue scale before and after the oral administration of the analgesics. Statistical analysis was performed using the Kruskal-Wallis test. RESULTS: All the analgesic groups showed a significant effect on the efficacy of the inferior alveolar nerve block in contrast to the control group (p<0.05). However, no significant difference was found between the drug groups on the effectiveness of the inferior alveolar nerve block (p>0.05). No side effects were reported in the present study. CONCLUSION: Preoperative analgesics significantly increase the effectiveness of inferior alveolar nerve block in patients with symptomatic irreversible pulpitis. Therefore, preoperative analgesics should be considered to increase the effectiveness of inferior alveolar nerve block in patients with symptomatic irreversible pulpitis on the mandibular molars. (EEJ-2023-02-033).

Effectiveness of Single Dose Premedication of Piroxicam and Prednisolone on Post Endodontic Pain in One Visit Root Canal Treatment: A Randomized Clinical Trial.

OBJECTIVE: The objective of this study was to compare the effectiveness of premedication drugs including single dose Piroxicam and Prednisolone in regard to post endodontic pain at different time intervals (24, 48, 72 and 96 hours) after single visit root canal treatment. METHODS: This randomized clinical trial (registration no. NCT04124822) was performed in operative dentistry department of a private clinical institute. One hundred twenty patients identified with symptomatic irreversible pulpitis were included in the study. The pain intensity levels were marked through the use of visual analog scale (VAS) before the commencement of treatment. The participants were randomly allocated in three groups, Group I (n=40) received no medication (control), Group II (n=40) received Piroxicam (20 mg) and Group III (n=40) received Prednisolone (20 mg). The drugs were administered thirty minutes before the endodontic procedure was initiated. Root canal treatmentwas carried out followed by placement of provisional restoration in a single appointment. The patients were instructed to continue marking their pain intensity levels after 24, 48, 72 and 96 hours using VAS. All patients were called for follow up after 4 days for clinical evaluation and the placement of permanent restoration. The effectiveness of each drug over different time interval was studied employing ANOVA test. The significance level was set at P≤0.05. RESULTS: The results of the present study revealed that a higher percentage of patients in all 3 groups, reported no post-operative pain at all evaluated time durations (24, 48, 72, and 96 hours). However, the long term effectiveness (96 hours) of both drugs to reduce post-endodontic pain was observed to be statistically insignificant. There was no significant difference in demographic data in terms of age (P=0.14), gender (P=0.12), whilst tooth type (P≤0.05) showed statistically significant value. CONCLUSION: Pre-medication with either single dose piroxicam or prednisolone was able to prevent post-endodontic pain in patients with symptomatic irreversible pulpitis.

[Possibilities of individual choice of NSAIDs on the example of the oxicam class, taking into account clinical and pharmacological characteristics]. / Vozmozhnosti individual'nogo podkhoda k vyboru nesteroidnogo protivovospalitel'nogo preparata dlya komorbidnogo patsienta s uchetom kliniko-farmakologicheskikh kharakteristik preparata na primere klassa oksikamov.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are traditionally used to relieve pain syndromes. The class of NSAIDs includes oxicams (meloxicam, tenoxicam, lornoxicam) - drugs with pronounced analgesic and anti-inflammatory effects. Oxicams have common properties of the class, but at the same time, due to structural differences from all other NSAIDs, they differ in a number of clinical and pharmacological characteristics, knowledge of which will help to individualize the choice of the drug.

Intra-Articular Piroxicam And Triamcinolone In A Ratmodel Of Osteoarthritis; Elevation And Comparison Of Chondroprotective Efficacy.

BACKGROUND: Osteoarthritis is the most common chronic degenerative joint disease. Definite treatment of osteoarthritis is still undiscovered. This study was designed to evaluate and compare the chondroprotective efficacy of piroxicam and triamcinolone in rat model of osteoarthritis. Methods: This laboratory based experimental study was conducted in Pharmacology Department, Army Medical College, Rawalpindi, from April-June 2019. Osteoarthritis was induced by medial meniscectomy and anterior cruciate ligament resection in knee joints of twenty-four rats. They were divided in three groups with eight rats in each. Group I, II and III were control, piroxicam and triamcinolone groups that were treated by intra articular saline, piroxicam and triamcinolone once weekly for four weeks respectively and then gait pattern was scored. Animals were euthanized thereafter and samples were taken for histopathological analysis. RESULTS: Comparison of gait score of control, piroxicam and triamcinolone groups exhibited a p-value of <0.01. Intergroup comparison of gait of group I and II, group I and III and group II and IV depicted pvalue of <0.001,0.013 and 0.013 respectively. Likewise histopathological comparison of control, piroxicam and triamcinolone groups showed p-value of <0.01. While Intergroup histopathological comparison of group I and II, group I and III and group II and IV showed p-value of <0.001, <0.001 and 0.008 respectively. Conclusion: Comparison of control group with treatment group proved chondroprotective efficacy of piroxicam and triamcinolone. On comparison of treatment groups, it was concluded that piroxicam has better chondroprotective efficacy as compared to triamcinolone.

Lapatinib as first-line treatment for muscle-invasive urothelial carcinoma in dogs.

Epidermal growth factor receptors 1 and 2 (EGFR and HER2) are frequently overexpressed in various malignancies. Lapatinib is a dual tyrosine kinase inhibitor that inhibits both EGFR and HER2. Although a phase III trial failed to show the survival benefits of lapatinib treatment after first-line chemotherapy in patients with EGFR/HER2-positive metastatic urothelial carcinoma, the efficacy of lapatinib for untreated urothelial carcinoma is not well defined. Here, we describe the therapeutic efficacy of lapatinib as a first-line treatment in a canine model of muscle-invasive urothelial carcinoma. In this non-randomized clinical trial, we compared 44 dogs with naturally occurring urothelial carcinoma who received lapatinib and piroxicam, with 42 age-, sex-, and tumor stage-matched dogs that received piroxicam alone. Compared to the dogs treated with piroxicam alone, those administered the lapatinib/piroxicam treatment had a greater reduction in the size of the primary tumor and improved survival. Exploratory analyses showed that HER2 overexpression was associated with response and survival in dogs treated with lapatinib. Our study suggests that lapatinib showed encouraging durable response rates, survival, and tolerability, supporting its therapeutic use for untreated advanced urothelial carcinoma in dogs. The use of lapatinib as a first-line treatment may be investigated further in human patients with urothelial carcinoma.

Piroxicam Loading onto Mesoporous Silicas by Supercritical CO2 Impregnation.

Piroxicam (PRX) is a commonly prescribed nonsteroidal anti-inflammatory drug. Its efficacy, however, is partially limited by its low water solubility. In recent years, different studies have tackled this problem and have suggested delivering PRX through solid dispersions. All these strategies, however, involve the use of potentially harmful solvents for the loading procedure. Since piroxicam is soluble in supercritical CO2 (scCO2), the present study aims, for the first time, to adsorb PRX onto mesoporous silica using scCO2, which is known to be a safer and greener technique compared to the organic solvent-based ones. For comparison, PRX is also loaded by adsorption from solution and incipient wetness impregnation using ethanol as solvent. Two different commercial mesoporous silicas are used (SBA-15 and Grace Syloid® XDP), which differ in porosity order and surface silanol population. Physico-chemical analyses show that the most promising results are obtained through scCO2, which yields the amorphization of PRX, whereas some crystallization occurs in the case of adsorption from solution and IWI. The highest loading of PRX by scCO2 is obtained in SBA-15 (15 wt.%), where molecule distribution appears homogeneous, with very limited pore blocking.

Piroxicam reduces acute and chronic pain response in type 1 diabetic rats.

OBJECTIVES: Pain associated with various underlying pathologies is a major cause of morbidity and diminished life quality in diabetic patients. Effective control of pain requires the use of analgesics with the best efficacy and with minimal side effects. Therefore, our aim in this study was to investigate the effects of non-steroidal anti-inflammatory drugs (NSAIDs) on pain in diabetic rats. METHODS: In this study, we investigated the analgesic effects of drugs belonging to three different classes of NSAIDs in a rat model of diabetes. Four diabetic groups received normal saline, diclofenac, piroxicam and ketorolac, respectively, and four non-diabetic groups received normal saline, diclofenac, piroxicam and ketorolac. Type 1 diabetes was induced in rats by a single injection of streptozotocin (60 mg/kg bw). Formalin (50 µL of 2.5%) nociception assay was used to examine the effect of treatment with diclofenac, piroxicam and ketorolac on acute and chronic pain in healthy and diabetic rats. RESULTS: Piroxicam showed significant analgesic effects both in the acute phase of pain (5-10 min after injection of formalin into the left hind paw), and in the chronic phase (20-60 min after formalin injection) in healthy as well as diabetic rats. Diclofenac and ketorolac also reduced pain scores in healthy rats. However, these two drugs failed to diminish pain in diabetic rats. CONCLUSION: Our data point for better efficacy of piroxicam in controlling pain in diabetes.

A combined protocol with piroxicam, chemotherapy, and whole pelvic irradiation with simultaneous boost volumetric modulated arc radiotherapy for muscle-invasive canine urinary transitional cell carcinoma: First clinical experience.

The aims of this pilot study were to evaluate the feasibility and efficacy of high-dose hypofractionated volumetric modulated arc radiotherapy (VMAT) applied to whole pelvic region radiotherapy (WPRT) with multilevel simultaneous integrated boost (MLSIB) combined with piroxicam and chemotherapy for the treatment of canine transitional cell carcinoma (TCC) of the lower urinary tract with muscle invasion TCC. Twelve dogs were enrolled, according to stage, in two groups: group 1, TCC confined to the urinary tract; group 2, TCC with metastasis. The planning target volume dose was tailored from 36 to 42 Gy in 6 fractions. All dogs were prescribed piroxicam and radiosensitizing carboplatin, and six received chemotherapy after radiotherapy. Serial follow-ups with computed tomography and magnetic resonance imaging were performed. Disease control and toxicity effects were evaluated according to the Response Evaluation Criteria in Solid Tumors and Veterinary Radiation Therapy Oncology Group criteria. The treatment was well tolerated, and no high-grade side effects were reported. The median overall survival times for groups 1 and 2 were 1,230 and 150 days, respectively. A considerable percentage of patients in group1 (50%) were still alive at the time of writing this paper, and a longer follow-up could enable a more accurate survival analysis. This preliminary analysis shows that VMAT applied to the WPRT with MLSIB is an effective and safe option for dogs with lower urinary TCC, although the presence of metastases worsens the prognosis.

Comparison of ibuprofen and piroxicam gel in the treatment of trauma pain: A randomized double-blind trial of geriatric population.

OBJECTIVE: This study aimed to compare the analgesic efficacy of topical ibuprofen and topical piroxicam for acute musculoskeletal injuries. METHODS: In this prospective, randomized, controlled, double-blinded study, geriatric patients were assigned to groups to receive either topical ibuprofen (n = 70) or topical piroxicam (n = 69). The first dose of gel was applied in the emergency department and the remaining doses were self-administered at home by the patients thrice daily for 72 h. For each patient, the initial baseline visual analog scale (VAS) score (V 0) was compared with the VAS scores at the 60 min (V1), 120 min (V2), 24 h (V3) and 72 h (V4) time points. The decreases in VAS scores, clinical effectiveness of the treatments, and incidence of adverse events were evaluated. RESULTS: In the topical ibuprofen group, the VAS scores were significantly lower at each measurement time point compared to baseline (p < .001). The results were as follows: V0 -V: 1.08, 95% CI: 0.56-1.61; V0 -V2: 1.09, 95% CI: 0.49-1.69; V0 -V3: 1.44, 95% CI: 0.81-2.07; V0 -V4: 1.59, 95% CI: 0.91-2.26. The mean percentage decrease in the VAS scores in the topical ibuprofen group was significantly higher than that in the topical piroxicam group (p < .001). The clinical effect of treatment was found to be significantly higher for the ibuprofen gel group (p < .001). There was no substantial difference in treatment-related adverse events between the groups (p > .05). CONCLUSION: Ibuprofen gel, which is a safe treatment option for geriatric patients, is more clinically effective than piroxicam gel. Response to Reviewers.

Impact of Non-Steroidal Anti-Inflammatory Drugs on Recurrence and Survival after Melanoma Surgery: A Cohort Study.

The aim of the study was to investigate if there was an association between intraoperative NSAID use and recurrence or survival. A cohort of patients who underwent sentinel lymph node biopsy for the treatment of cutaneous melanoma was retrospectively recruited. After applying inclusion and exclusion criteria, 516 were included (NSAIDs = 307). The 10-year melanoma-specific survival was 63.2%. Log-rank test showed no statistically significant differences in time to treatment failure, melanoma-specific survival, disease-free survival, and overall survival between the study groups. The current study did not support the use of intraoperative NSAIDs in preventing death or recurrence in patients with melanoma.

Comparison of intradermal mesotherapy with systemic therapy in the treatment of low back pain: A prospective randomized study.

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.

A comparative study on anti-inflammatory drug combinations in domestic pigeons with experimentally induced acute arthritis.

The study compares the effect of one-time administration of nonsteroidal and/or steroidal anti-inflammatory combinations by topical or intramuscular (IM) routes to pigeons with monosodium urate (MSU)-induced arthritis. Forty-five adult domestic pigeons were assigned into nine equal groups: NC, negative control; PC, positive control with arthritis; sham, sham control; T1, meloxicam + hydrocortisone; T2, dexamethasone + piroxicam; T3, meloxicam + dexamethasone; T4, hydrocortisone + piroxicam; T5, dexamethasone + hydrocortisone; T6, meloxicam + piroxicam. Arthritis was also induced in T1 to T6 birds. Meloxicam and dexamethasone were administered by IM injection and the other drugs topically right after the induction of arthritis. Different drug combinations significantly decreased one-leg standing time. Induction of arthritis significantly increased TNF-α and IL-6 levels in synovial fluid and serum corticosterone and epinephrine in the PC group. Administration of drugs to birds of Groups T1 and T5 did not significantly change corticosterone concentration, while all different drug combinations decreased epinephrine level. Drug combinations that demonstrated better analgesic effect more strongly reduced serum epinephrine concentration. Meloxicam + hydrocortisone was the most effective combination in reducing inflammatory cytokines. In conclusion, one-time combination therapy with anti-inflammatory agents was effective in the acute management of inflammatory pain due to MSU-induced arthritis in pigeons, even by the topical route.

Oral non-steroidal anti-inflammatory drug therapy for lung disease in cystic fibrosis.

BACKGROUND: Progressive lung damage causes most deaths in cystic fibrosis. Non-steroidal anti-inflammatory drugs (such as ibuprofen) may prevent progressive pulmonary deterioration and morbidity in cystic fibrosis. This is an update of a previously published review. OBJECTIVES: To assess the effectiveness of treatment with oral non-steroidal anti-inflammatory drugs in cystic fibrosis. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, hand searches of relevant journals and abstract books of conference proceedings. We contacted manufacturers of non-steroidal anti-inflammatory drugs and searched online trials registries.Latest search of the Group's Trials Register: 21 November 2018. SELECTION CRITERIA: Randomized controlled trials comparing oral non-steroidal anti-inflammatory drugs, at any dose for at least two months, to placebo in people with cystic fibrosis. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trials for inclusion the review and their potential risk of bias. Two authors independently rated the quality of the evidence for each outcome using the GRADE guidelines. MAIN RESULTS: The searches identified 17 trials; four are included (287 participants aged five to 39 years; maximum follow-up of four years) and one is currently awaiting classification pending publication of the full trial report and two are ongoing. Three trials compared ibuprofen to placebo (two from the same center with some of the same participants); one trial assessed piroxicam versus placebo.The three ibuprofen trials were deemed to have good or adequate methodological quality, but used various outcomes and summary measures. Reviewers considered measures of lung function, nutritional status, radiological assessment of pulmonary involvement, intravenous antibiotic usage, hospital admissions, survival and adverse effects. Combined data from the two largest ibuprofen trials showed a lower annual rate of decline for lung function, % predicted forced expiratory volume in one second (FEV1), mean difference (MD) 1.32 (95% confidence interval (CI) 0.21 to 2.42) (moderate-quality evidence); forced vital capacity (FVC), MD 1.27 (95% CI 0.26 to 2.28) (moderate-quality evidence); forced expiratory flow (FEF25%-75%), MD 1.80 (95% CI 0.15 to 3.45). The post hoc analysis of data from two trials split by age showed a slower rate of annual decline of FEV1 % predicted and FVC in the ibuprofen group in younger children, MD 1.41% (95% CI 0.03 to 2.80) (moderate-quality evidence) and MD 1.32% (95% CI 0.04 to 2.60) (moderate-quality evidence) respectively. Data from four trials demonstrated the proportion of participants with at least one hospitalization may be slightly lower in the ibuprofen group compared to placebo, Peto odds ratio 0.61 (95% CI 0.37 to 1.01) (moderate-quality evidence). In one trial, long-term use of high-dose ibuprofen was associated with reduced intravenous antibiotic usage, improved nutritional and radiological pulmonary status. No major adverse effects were reported, but the power of the trials to identify clinically important differences in the incidence of adverse effects was low.We did not have any concerns with regards to risk of bias for the trial comparing piroxicam to placebo. However, the trial did not report many data in a form that we could analyze in this review. No data were available for the review's primary outcome of lung function; available data for hospital admissions showed no difference between the groups. No analyzable data were available for any other review outcome. AUTHORS' CONCLUSIONS: High-dose ibuprofen can slow the progression of lung disease in people with cystic fibrosis, especially in children, which suggests that strategies to modulate lung inflammation can be beneficial for people with cystic fibrosis.

Inhibidores de ciclooxigenasa para impedir la vitreorretinopatía proliferativa: ¿aptos para uso clínico? / Cyclooxygenases inhibitors for preventing the proliferative vitreoretinopathy: Ready for clinical use?

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A combination therapy of nanoethosomal piroxicam formulation along with iontophoresis as an anti-inflammatory transdermal delivery system for wound healing.

Inflammation accounts as one of the major phases in wound healing, while prolonged and chronic inflammation may lead to adverse pathological conditions. Therefore, transdermal delivery of nonsteroidal anti-inflammatory (NSAIDs) such as encapsulated piroxicam into a nanocarrier seems to be promising. For the first time, a nanoethosomal piroxicam of <200 nm was prepared and combined with iontophoresis. Results showed that there was a critical point at the concentration of 5 mg lecithin with the smallest particle size. Besides, lecithin concentration had direct and inverse linear relationships with turbidity and pH of nanocarriers, respectively. Moreover, as there was no linear relationship between the lecithin concentration and particle size, the effect of lecithin concentration was dominant on turbidity compared with particle size. It seems that a pH higher than 5.5 disturbed the linear relationship of pH and entrapment efficacy percentage (EE%) while at the pH range of 4 to 5.5, the relationship was linear and EE% gradually decreased with increasing pH. These data showed that an optimised nanocarrier with special physicochemical properties is dominant to the just particle size. Besides, ex vivo permeation studies in rat skin showed that there was no significant difference between the permeation of free drug and ethosomal ones. However, iontophoresis significantly enhanced ethosomal piroxicam permeation compared with the free drug. Overall, these data emphasise the superiority of iontophoresis for the transdermal delivery of nanoethosomal medications while nanoethosomal delivery without iontophoresis did not show significant transdermal potential. To sum up, transdermal nanoethosomal piroxicam along with iontophoresis seems to be promising in wound healing.

Enhanced transdermal delivery of lornoxicam by nanostructured lipid carrier gels modified with polyarginine peptide for treatment of carrageenan-induced rat paw edema.

Background: Nanostructured lipid carriers (NLCs) are emerging as attractive drug carriers in transdermal drug delivery. The surface modification of NLCs with cell-penetrating peptides (CPPs) can enhance the skin permeation of drugs. Purpose: The objective of the current study was to evaluate the ability of the cell-penetrating peptide (CPP) polyarginine to translocate NLCs loaded with lornoxicam (LN) into the skin layers and to evaluate its anti-inflammatory effect. Methods: The NLCs were prepared using an emulsion evaporation and low temperature solidification technique using glyceryl monostearates, triglycerides, DOGS-NTA-Ni lipids and surfactants, and then six histidine-tagged polyarginine containing 11 arginine (R11) peptides was modified on the surface of NLCs. Results: The developed NLCs formulated with LN and R11 (LN-NLC-R11) were incorporated into 2% HPMC gels. NLCs were prepared with a particle size of (121.81±3.61)-(145.72±4.78) nm, and the zeta potential decreased from (-30.30±2.07) to (-14.66±0.74) mV after the modification of R11 peptides. The encapsulation efficiency and drug loading were (74.61±1.13) % and (7.92±0.33) %, respectively, regardless of the surface modification. Cellular uptake assays using HaCaT cells suggested that the NLC modified with R11 (0.02%, w/w) significantly enhanced the cell internalization of nanoparticles relative to unmodified NLCs (P<0.05 or P<0.01). An in vitro skin permeation study showed better permeation-enhancing ability of R11 (0.02%, w/w) than that of other content (0.01% or 0.04%). In carrageenan-induced rat paw edema models, LN-NLC-R11 gels inhibited rat paw edema and the production of inflammatory cytokines compared with LN-NLC gels and LN gels (P<0.01). Conclusion: In our investigation, it was strongly demonstrated that the surface modification of NLC with R11 enhanced the translocation of LN across the skin, thereby alleviating inflammation.