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1.
Nutrients ; 16(6)2024 Mar 09.
Article in English | MEDLINE | ID: mdl-38542694

ABSTRACT

A three-arm, randomized, placebo-controlled clinical study was conducted to assess the impact of lyophilized pineapple extract with titrated bromelain (Brome-Inf®) and purified bromelain on pain, swelling, trismus, and quality of life (QoL) following the surgical extraction of the mandibular third molars. Furthermore, this study examined the need for Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) by comparing their effects with a placebo group. This study enrolled 42 individuals requiring the extraction of a single mandibular third molar under local anesthesia. The patients were randomly assigned to receive Brome-Inf®, purified bromelain, or a placebo orally, initiating treatment on the day of surgery and continuing for the next 7 days. The primary outcome measured was the requirement for NSAIDs in the three groups. Pain, swelling, and trismus were secondary outcome variables, evaluated postoperatively at 1, 3, and 7 days. This study also assessed the comparative efficacy of freeze-dried pineapple extract and single-component bromelain. Ultimately, the placebo group showed a statistically higher need for ibuprofen (from days 1 to 7) at the study's conclusion (p < 0.0001). In addition, reductions in pain and swelling were significantly higher in both the bromelain and pineapple groups (p < 0.0001 for almost all patients, at all intervals) than in the placebo group. The active groups also demonstrated a significant difference in QoL compared to the placebo group (p < 0.001). A non-significant reduction in trismus occurred in the treatment groups compared to the placebo group. Therefore, the administration of pineapple extract titrated in bromelain showed significant analgesic and anti-edema effects in addition to improving QoL in the postoperative period for patients who had undergone mandibular third molar surgery. Moreover, both bromelain and Brome-Inf® supplementation reduced the need for ibuprofen to comparable extents, proving that they are good alternatives to NSAIDs in making the postoperative course more comfortable for these patients. A further investigation with larger samples is necessary to assess the pain-relieving and anti-inflammatory impacts of the entire pineapple phytocomplex in surgical procedures aside from mandibular third molar surgery.


Subject(s)
Ananas , Ibuprofen , Humans , Ibuprofen/therapeutic use , Molar, Third/surgery , Quality of Life , Pain, Postoperative/drug therapy , Bromelains/therapeutic use , Trismus/drug therapy , Trismus/etiology , Trismus/prevention & control , Anti-Inflammatory Agents/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Edema/drug therapy , Edema/etiology , Edema/prevention & control , Tooth Extraction/adverse effects
2.
Lancet Rheumatol ; 6(4): e205-e215, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38458208

ABSTRACT

BACKGROUND: Multimodal postoperative analgesia following total hip arthroplasty is recommended, but the optimal combination of drugs remains uncertain. The aim of the RECIPE trial was to investigate the relative benefit and harm of the different combinations of paracetamol, ibuprofen, and the analgesic adjuvant dexamethasone for treatment of postoperative pain following total hip arthroplasty. METHODS: The RECIPE trial was a randomised, blinded, placebo-controlled trial conducted at nine Danish hospitals. Adults scheduled for total hip arthroplasty were randomly assigned (1:1:1:1) using a computer-generated list with stratification by site to receive combinations of oral paracetamol 1000 mg every 6 h, oral ibuprofen 400 mg every 6 h, or a single-dose of intravenous dexamethasone 24 mg in the following groups: paracetamol plus ibuprofen, ibuprofen plus dexamethasone, paracetamol plus dexamethasone, and paracetamol plus ibuprofen plus dexamethasone. The primary outcome was 24 h intravenous morphine consumption, analysed in a modified intention-to-treat population, defined as all randomly assigned participants who underwent total hip arthroplasty. The predefined minimal important difference was 8 mg. Safety outcomes included serious and non-serious adverse events within 90 days and 24 h. The trial was registered with ClinicalTrials.gov, NCT04123873. FINDINGS: Between March 5, 2020, and Nov 15, 2022, we randomly assigned 1060 participants, of whom 1043 (589 [56%] women and 454 [44%] men) were included in the modified intention-to-treat population. 261 were assigned to paracetamol plus ibuprofen, 262 to ibuprofen plus dexamethasone, 262 to paracetamol plus dexamethasone, and 258 to paracetamol plus ibuprofen plus dexamethasone. Median 24 h morphine consumption was 24 mg (IQR 12-38) in the paracetamol plus ibuprofen group, 20 mg (12-32) in the paracetamol plus dexamethasone group, 16 mg (10-30) in the ibuprofen plus dexamethasone group, and 15 mg (8-26) in the paracetamol plus ibuprofen plus dexamethasone group. The paracetamol plus ibuprofen plus dexamethasone group had a significantly reduced 24 h morphine consumption compared with paracetamol plus ibuprofen (Hodges-Lehmann median difference -6 mg [99% CI -10 to -3]; p<0·0001) and paracetamol plus dexamethasone (-4 mg [-8 to -1]; p=0·0013), however, none of the comparisons showed differences reaching the minimal important threshold of 8 mg. 91 (35%) of 258 participants in the paracetamol plus ibuprofen plus dexamethasone group had one or more adverse events, compared with 99 (38%) of 262 in the ibuprofen plus dexamethasone group, 103 (39%) of 262 in the paracetamol plus dexamethasone group, and 165 (63%) of 261 in the paracetamol plus ibuprofen group. INTERPRETATION: In adults undergoing total hip arthroplasty, a combination of paracetamol, ibuprofen, and dexamethasone had the lowest morphine consumption within 24 h following surgery and the most favourable adverse event profile, with a lower incidence of serious and non-serious adverse events (primarily driven by differences in nausea, vomiting, and dizziness) compared with paracetamol plus ibuprofen. FUNDING: The Novo Nordisk Foundation and Næstved-Slagelse-Ringsted Hospitals' Research Fund.


Subject(s)
Analgesics, Non-Narcotic , Arthroplasty, Replacement, Hip , Male , Adult , Humans , Female , Analgesics, Non-Narcotic/therapeutic use , Acetaminophen/therapeutic use , Ibuprofen/adverse effects , Arthroplasty, Replacement, Hip/adverse effects , Drug Therapy, Combination , Morphine/adverse effects , Dexamethasone/adverse effects
3.
J Bodyw Mov Ther ; 37: 156-163, 2024 01.
Article in English | MEDLINE | ID: mdl-38432799

ABSTRACT

BACKGROUND: The management of acute postoperative pain after rotator cuff surgery can be challenging. To our knowledge, there are no data available in the literature correlating satisfactory pain control with improvement in terms of function. The purposes of the present study were to evaluate: 1) pain pattern after arthroscopic rotator cuff repair in patients operated with two different techniques (transosseous vs transosseous equivalent); 2) safety/efficacy of three different pharmacological pain control strategies; 3) possible relationship between a correct shoulder pain management protocol in the early post-operative period and patients' functional improvement. METHODS: 114 patients underwent rotator cuff tear repair, either with a Transosseus or a Transosseus equivalent technique. 62 (54%) were male and 52 (46%) were female. The average age was 59 ± 9 years. They were randomly assigned into three different pain management protocols: Paracetamol as needed (max 3 tablets/day) for 1 week (Protocol A), Paracetamol + Codein 1 tablet three times per day for 7 days (Protocol B), or Paracetamol + Ibuprofen 1 tablet two times per day for 7 days (Protocol C). Immediate passive mobilization of the operated shoulder was allowed. VAS and Passive Flexion values were recorded at 7 (T1), 15 (T2) and 30 (T3) days post-surgery. DASH values were recorded at 90 days post-surgery. All patients were asked to register any kind of signs/symptoms that may appear during drug assumption according to each pain management protocols. RESULTS: All the pain management protocols administered were well tolerated by all the study population, and no adverse signs/symptoms were highlighted during drug assumption. Pain pattern: in both surgical techniques, patients within Protocol A were associated with worst results in terms of mean VAS at each time point examined when compared to Protocol B and C (p < 0,05). In patients within Protocol A, no statistically significant differences were found at each point time examined comparing the two surgical techniques, with the exception of T2, where the TO was associated with an higher VAS value than TOE (p < 0.05). No differences were highlighted in Protocol B and C when comparing the values between two surgical techniques. ROM: in both surgical techniques, patients within Protocol A were associated with worst results in terms of mean PROM at each time point examined when compared to Protocol B and C (p < 0,05). In the TO group, patients within Protocol B had better PROM values at T1 (p < 0,05) and T2 (p < 0,05) compared to Protocol C, but no differences were highlighted at T3. In the TOE group, no statistically significant differences were found between patients within Protocol B and C at each time point examined. DASH: In the TO group, no statistically significant differences were found regarding the DASH values comparing Protocol B vs Protocol C, but they were highlighted comparing the values between Protocol A and Protocol B (p < 0,05), and between Protocol A and Protocol C (p < 0,05). Similar results were recorded in the TOE group. CONCLUSION: Post-operative pain is influenced by the surgical technique used being transosseous more painful in the first 15 days after surgery. Oral anti-inflammatory drugs are a feasible strategy to appropriately control post-operative pain. An association between Paracetamol and either Codein or Ibuprofen can lead to better outcomes in terms of VAS reduction and early recovery of passive ROM.


Subject(s)
Rotator Cuff Injuries , Shoulder , Humans , Female , Male , Middle Aged , Aged , Pain Management , Rotator Cuff Injuries/surgery , Acetaminophen , Ibuprofen , Shoulder Pain/therapy , Pain, Postoperative/drug therapy , Tablets
4.
J Food Sci ; 89(3): 1739-1754, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38349052

ABSTRACT

The aim of this study was to evaluate the effect of Citrus sinensis essential oil (EO) on the proximate composition of yogurt over a 28-day shelf life and to investigate the therapeutic and prophylactic effects of functional yogurt on ibuprofen-induced gastric ulcers in a rat model. It was observed that the yogurt group containing C. sinensis EO had higher acidity, total solids, and ash values. Histologic evaluation of the stomachs of rats with gastric ulcers revealed that rats fed with functional yogurt had fewer lesions compared to the control group. The treatment group had fewer lesions than the positive control (p > 0.05). Lesions in the glandular mucosa of the prophylactic group were significantly lower than those in the positive control group (p < 0.05). Yogurt with C. sinensis EO may be beneficial in reducing the severity of ulcers and improving overall health.


Subject(s)
Citrus sinensis , Oils, Volatile , Stomach Ulcer , Humans , Rats , Animals , Aged , Stomach Ulcer/chemically induced , Stomach Ulcer/drug therapy , Stomach Ulcer/prevention & control , Ibuprofen/adverse effects , Yogurt , Oils, Volatile/pharmacology , Gastric Mucosa
5.
Zhongguo Zhen Jiu ; 44(2): 134-138, 2024 Feb 12.
Article in English, Chinese | MEDLINE | ID: mdl-38373756

ABSTRACT

OBJECTIVES: To compare the clinical effect between inverted T-shaped herb-separated moxibustion combined with western medication and simple western medication on chronic pelvic pain(CPP)in sequelae of pelvic inflammatory diseases. METHODS: A total of 60 patients with CPP in sequelae of pelvic inflammatory diseases were randomly divided into an observation group and a control group, 30 cases in each group. The control group was given ibuprofen tablets 10 days before menstruation, 0.2 g each time, once a day for 10 days. After menstruation, the medication was stopped, and the treatment was given for 3 menstrual cycles.On the basis of the treatment in the control group, the observation group was treated with inverted T-shaped herb-separated moxibustion at the connection between Zhongwan(CV 12)and Zhongji(CV 3), and the connection between Zigong(EX-CA 1)on both sides.The treatment was performed once a week, with an interval of 6 days. The moxibustion was stopped during the menstrual period, the treatment was given for 3 menstrual cycles.Before and after treatment, the visual analogue scale(VAS)score of lower abdominal and lumbosacral pain, local symptom (uterine tenderness, adnexal tenderness and uterosacral ligament tenderness) score and quality of life assessment (QOL) score of the two groups were observed. RESULTS: After treatment, the lower abdominal and lumbosacral pain VAS scores, the local symptom scores of uterine tenderness, adnexal tenderness, uterosacral ligament tenderness and total scores in the two groups were lower than those before treatment(P<0.01).The lower abdominal and lumbosacral pain VAS score in the observation group was lower than that in the control group(P<0.01),and the changes of local symptom scores of uterine tenderness, adnexal tenderness and uterosacral ligament tenderness and total score in the observation group were greater than those in the control group(P<0.01). After treatment, the QOL scores of the two groups were higher than those before treatment(P<0.01), and the score in the observation group was higher than that in the control group(P<0.01). CONCLUSIONS: Inverted T-shaped herb-separated moxibustion combined with western medication can effectively reduce the pain in patients with CPP in sequelae of pelvic inflammatory diseases, relieve the local symptoms, improve the quality of life, and the curative effect is better than western medication alone.


Subject(s)
Moxibustion , Pelvic Inflammatory Disease , Female , Humans , Quality of Life , Pelvic Inflammatory Disease/complications , Pelvic Inflammatory Disease/therapy , Ibuprofen , Pelvic Pain/etiology , Pelvic Pain/therapy , Acupuncture Points , Treatment Outcome
6.
Langmuir ; 40(10): 5098-5105, 2024 03 12.
Article in English | MEDLINE | ID: mdl-38412279

ABSTRACT

As a serious public health issue, malaria threatens the health of millions of people. Artemisinin, a gift from traditional Chinese medicine, has been used in the treatment of malaria and has shown good therapeutic efficiency. However, due to its low solubility, poor bioavailability, and short half-life time, some smart delivery strategies are still required. Herein, a multifunctional DES prepared from ibuprofen and menthol was prepared. This DES was shown to efficiently promote the solubility of artemisinin up to 400-fold. Then, it was further applied as the oil phase to construct an O/W microemulsion with the help of Tween-80 + Span-20 mixed surfactants. The prepared microemulsion displayed high efficiency in improving the permeability of artemisinin, which can be ascribed to the presence of the permeation enhancer menthol in DES and the microstructure of the O/W microemulsion. Moreover, the simultaneous permeation of artemisinin and ibuprofen further indicated the potential benefits of the presented formulation in the treatment of malaria. To sum up, the microemulsion based on multifunctional DES presented herein provided an effective method for transdermal delivery of artemisinin.


Subject(s)
Artemisinins , Malaria , Humans , Ibuprofen/chemistry , Deep Eutectic Solvents , Solvents , Drug Delivery Systems/methods , Menthol , Emulsions/chemistry , Administration, Cutaneous , Surface-Active Agents/chemistry , Malaria/drug therapy
7.
Medicine (Baltimore) ; 103(4): e36997, 2024 Jan 26.
Article in English | MEDLINE | ID: mdl-38277537

ABSTRACT

RATIONALE: Previous studies have shown that acetaminophen has the potential to induce hepatotoxicity in patients, rendering it a prominent drug implicated in the development of acute hepatic failure. However, there is currently no available literature reporting the impact of ibuprofen-sustained release capsules on liver failure. PATIENT CONCERNS: A 65-year-old man was presented with a 4-day history of tea-colored urine with oil avoidance, jaundiced skin, and anorexia, and impaired liver function. One ibuprofen-sustained release capsule was taken on the day before the onset of the disease due to "headache." DIAGNOSES: A diagnosis of this patient was made of liver failure due to taking ibuprofen-sustained release capsules. INTERVENTIONS: Initially, the patient discontinued the use of hepatotoxic drugs in order to prevent further exposure. Subsequently, the patient underwent a standard therapeutic regimen, which encompassed the administration of hepatoprotective agents, nutritional support drugs, correction of acid-base imbalances, and electrolyte abnormalities, as well as other relevant treatments. OUTCOMES: After 9 days of hepatoprotective and nutritional supplement therapy, the patient saw notable improvement in symptoms, reporting an absence of discomfort, subsided skin jaundice, clear urine, and liver function tests returning to a near normal range. The patient was granted permission to be discharged from the hospital while being prescribed drugs. After 2 weeks of follow-up, the patient reported an absence of discomfort and exhibited normal results in the liver function test. CONCLUSIONS: Liver failure caused by ibuprofen-sustained release capsules has not been reported. It is worth noting that conventional treatments such as suspending offending agents, and administration of hepatoprotective agents and nutritional support drugs have proven to be successful. LESSON: There is currently no known peer-reviewed literature indicating that the administration of ibuprofen-sustained release capsules leads to liver failure. When patients taking ibuprofen-sustained release capsules encounter symptoms such as anorexia, skin jaundice, lack of appetite, and nausea, it is recommended that they undertake a cardiac and liver function tests. In the event that ibuprofen-sustained release capsules induce liver injury, it is imperative to administer timely and immediate medical intervention.


Subject(s)
Jaundice , Liver Failure , Male , Humans , Aged , Ibuprofen/adverse effects , Delayed-Action Preparations/adverse effects , Anorexia , Capsules , Liver Failure/chemically induced
8.
Arch Oral Biol ; 160: 105893, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38271891

ABSTRACT

OBJECTIVE: This study evaluated the effects of intramuscular ozone therapy on nociception, inflammation, and tissue damage caused by the injection of carrageenan in the masseter muscle of rats. DESIGN: Rat masseter muscles were injected with saline or carrageenan. Seventy-seven adult male rats were divided into six groups: Sal, saline; Car, carrageenan; Ibup + Sal, ibuprofen and saline; Ibup + Car, ibuprofen and carrageenan; O3 + Sal, ozone and saline; and O3 + Car, ozone and carrageenan. The mixture of 5% ozone and 95% oxygen (20 µg/mL) was administered three times in the course of a week. Nociceptive responses in the masseter muscles were measured using a head withdrawal threshold, determined by an electronic von Frey anesthesiometer. The animals were euthanized one or eight days after the carrageenan injection, and the masseters were submitted to histological and histomorphometric analyses. RESULTS: Mechanical allodynia and inflammation levels were reduced in the Ibup + Car group compared to the other groups. Myonecrosis was similar among carrageenan-treated groups. Picrosirius red stained sections showed more collagen fibers and more regenerating myofibers in the O3 + Car group compared to the other groups. Eight days after carrageenan injection, the O3 + Car group showed neutrophils close to the regenerating myofibers. CONCLUSIONS: Intramuscular ozone therapy did not alleviate mechanical allodynia, and it did not protect the masseter muscle against the deleterious effects produced by carrageenan, probably due to the mode of administration of this therapeutic agent.


Subject(s)
Hyperalgesia , Masseter Muscle , Rats , Male , Animals , Masseter Muscle/physiology , Hyperalgesia/chemically induced , Hyperalgesia/drug therapy , Carrageenan/pharmacology , Rats, Sprague-Dawley , Nociception , Ibuprofen/pharmacology , Inflammation/pathology , Pain
9.
Fitoterapia ; 172: 105747, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37977305

ABSTRACT

Heishunpian is obtained through complex processing of Aconiti lateralis radix praeparata. However, the impact of each processing step on chemical compositions and pharmacological activities is still unclear. The mechanism of the processing needs to be further studied. The samples were all prepared using the "step knockout" strategy for UPLC-QTOF-MS analysis, and analgesic and anti-inflammatory efficacy evaluation. Each sample was analyzed by UPLC-QTOF-MS to determine the component differences. The hot plate test and acetic acid writhing test were used to evaluate the analgesic effect. Anti-inflammatory efficacy was evaluated by xylene-induced ear edema test. The correlation between components and efficacies was studied to screen the effective components for further investigating the processing of Heishunpian. Mass spectrum analysis results showed that 49 components were identified, and it appeared that brine immersion and rinsing had a great influence on the components. In the hot plate test, ibuprofen and Heishunpian had the most significant effect, while ibuprofen and the sample without rinsing showed the best efficacy for the acetic acid writhing test. The sample without dyeing had the best effect on ear edema. The correlation analysis indicated that mesaconine, aconine, 3-deoxyaconine, delbruine, and asperglaucide were potentially considered effective analgesic components. It is not recommended to remove brine immersion and rinsing. Boiling and steaming are necessary processes that improve efficacy. Dyeing, which does not have a significant impact on components and efficacy, may be an unnecessary process. This research has been of great significance in identifying anti-inflammatory and analgesic components and optimizing processing for Heishunpian.


Subject(s)
Aconitum , Drugs, Chinese Herbal , Salts , Ibuprofen , Molecular Structure , Drugs, Chinese Herbal/chemistry , Analgesics/pharmacology , Anti-Inflammatory Agents/pharmacology , Aconitum/chemistry , Edema/chemically induced , Edema/drug therapy , Acetates
10.
PLoS One ; 18(12): e0295115, 2023.
Article in English | MEDLINE | ID: mdl-38060549

ABSTRACT

INTRODUCTION: Neck pain poses enormous individual and societal costs worldwide. Spinal manipulative therapy and Non-Steroidal Anti-Inflammatory Drug treatment are frequently used despite a lack of compelling efficacy data. This protocol describes a multicentre 4-arm, clinical placebo randomized controlled trial (RCT), investigating the efficacy of chiropractic spinal manipulative therapy (CSMT) versus sham CSMT, ibuprofen, and placebo medicine for acute neck pain. This superiority study will employ parallel groups, featuring a 1:1:1:1 allocation ratio. MATERIAL AND METHODS: We will randomize 320 participants equally into four groups: CSMT, sham CSMT, ibuprofen, or placebo medicine. CSMT groups are single-blinded, while the medicine groups are double-blinded. Data will be collected at baseline (Day 0), during treatment and post-treatment. The primary endpoint will assess the difference in mean pain intensity from Day 0 to Day 14 on a numeric rating scale 0-10; the CSMT group is compared to sham CSMT, ibuprofen, and placebo medicine groups, respectively. Secondary endpoints will assess mean pain intensity and mean duration at different time points, and adverse events, blinding success, and treatment satisfaction, including comparison between ibuprofen and placebo medicine. Power calculation is based on a mean neck pain rating of 5 at Day 0, with standard deviation of 1 in all groups. Mean pain reduction at Day 14 is expected to be 60% in the CSMT group, 40% in sham CSMT and ibuprofen groups, and 20% in the placebo medicine group. A linear mixed model will compare the mean values for groups with corresponding 95% confidence intervals. P values below 0.017 will be considered statistically significant. All analyses will be conducted blinded from group allocation. DISCUSSION: This RCT aims towards the highest research standards possible for manual-therapy RCTs owing to its two placebo arms. If CSMT and/or ibuprofen proves to be effective, it will provide evidence-based support for CSMT and/or ibuprofen for acute neck pain. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05374057. EU Clinical Trials Register: EudraCT number: 2021-005483-21.


Subject(s)
Acute Pain , Chiropractic , Manipulation, Spinal , Humans , Ibuprofen/therapeutic use , Neck Pain/therapy , Prospective Studies , Randomized Controlled Trials as Topic , Multicenter Studies as Topic
11.
BMC Complement Med Ther ; 23(1): 464, 2023 Dec 16.
Article in English | MEDLINE | ID: mdl-38104070

ABSTRACT

BACKGROUND: The plant kingdom has long been considered a valuable source for therapeutic agents, however, some plant species still untapped and need to be phytochemically and biologically explored. Although several Atriplex species have been investigated in depth, A. leucoclada, a halophytic plant native to Saudi Arabian desert, remains to be explored for its phytochemical content and biological potentials. Herein, the current study investigated the metabolic content and the anti-inflammatory potential of A. leucoclada. METHODS: Powdered aerial parts of the plant were defatted with n-hexane then the defatted powder was extracted with 80% methanol. n-Hexane extract (ATH) was analyzed using GC-MS, while the defatted extract (ATD) was subjected to different chromatographic methods to isolate the major phytoconstituents. The structures of the purified compounds were elucidated using different spectroscopic methods including advanced NMR techniques. Anti-inflammatory activity of both extracts against COX-1 and COX-2 enzymes were examined in vitro. Molecular docking of the identified compounds into the active sites of COX-1 and COX-2 enzymes was conducted using pdb entries 6Y3C and 5IKV, respectively. RESULTS: Phytochemical investigation of ATD extract led to purification and identification of nine compounds. Interestingly, all the compounds, except for 20-hydroxy ecdysone (1), are reported for the first time from A. leucoclada, also luteolin (6) and pallidol (8) are isolated for the first time from genus Atriplex. Inhibitory activity of ATD and ATH extracts against COX-1 and COX-2 enzymes revealed concentration dependent activity of both fractions with IC50 41.22, 14.40 µg/ml for ATD and 16.74 and 5.96 µg/ml for ATH against COX-1 and COX-2, respectively. Both extracts displayed selectivity indices of 2.86 and 2.80, respectively as compared to 2.56 for Ibuprofen indicating a promising selectivity towards COX-2. Molecular docking study supported in vitro testing results, where purified metabolites showed binding affinity scores ranged from -9 to -6.4 and -8.5 to -6.6 kcal/mol for COX-1 and 2, respectively, in addition the binding energies of GC-MS detected compounds ranged from -8.9 to -5.5 and -8.3 to -5.1 kcal/mol for COX-1 and 2, respectively as compared to Ibuprofen (-6.9 and -7.5 kcal/mol, respectively), indicating high binding affinities of most of the compounds. Analysis of the binding orientations revealed variable binding patterns depending on the nature of the compounds. Our study suggested A. leucoclada as a generous source for anti-inflammatory agents.


Subject(s)
Atriplex , Atriplex/metabolism , Plant Extracts/chemistry , Molecular Docking Simulation , Cyclooxygenase 2/metabolism , Ibuprofen , Saudi Arabia , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Phytochemicals/pharmacology , Phytochemicals/chemistry
12.
Dent Med Probl ; 60(4): 619-625, 2023.
Article in English | MEDLINE | ID: mdl-37905456

ABSTRACT

BACKGROUND: Pain is the most prevalent complication after dentoalveolar surgery. Failure in effective pain control could potentially lead to systemic sequels, such as tachycardia, hypertension, improper nutrition, and central sensitization. Pregabalin is a gamma-aminobutyric acid (GABA) analog with inhibitory and analgesic effects on the central nervous system (CNS). Prescribing gabapentinoids as complementary analgesics reduces the consumption of opioid and non-opioid analgesics, and consequently their side effects. OBJECTIVES: The main purpose of the present study was to compare the analgesic effects of pregabalin (single-dose 75 mg) vs. ibuprofen (single-dose 400 mg) on patients' pain levels after impacted third mandibular molar surgery. MATERIAL AND METHODS: In this randomized, double-blind, split-mouth clinical trial, 24 patients aged 19-34 years volunteered for 2 consecutive (1 month apart) third mandibular molar surgeries (the contralateral teeth). The patients were randomly placed into 2 groups: group G1 (n = 12) was prescribed pregabalin (single-dose 75 mg) after the 1st surgery and ibuprofen (single-dose 400 mg) after the 2nd surgery; and group G2 (n = 12) was prescribed the exact opposite of the G1 arrangement. During the first 24 h post-surgery, the patients recorded the number of complementary analgesics they took (single-dose 400 mg ibuprofen) and their level of pain on a visual analog scale (VAS) every 2 h. RESULTS: The average level of pain at 2 h post-surgery (T1) was significantly lower when pregabalin was prescribed (p < 0.05). Most patients needed complementary analgesics at 4 h post-surgery (T2). However, during the first 24 h post-surgery, the patients required significantly more complementary analgesics when ibuprofen was prescribed. CONCLUSIONS: In comparison with oral ibuprofen (single-dose 400 mg), oral pregabalin (single-dose 75 mg) had a stronger analgesic effect at 2 h after impacted third mandibular molar surgery (p < 0.05). Pregabalin resulted in a significantly lower consumption of complementary analgesics in the first 24 h post-surgery as compared to ibuprofen.


Subject(s)
Ibuprofen , Tooth, Impacted , Humans , Analgesics/adverse effects , Ibuprofen/therapeutic use , Molar, Third/surgery , Pain, Postoperative/drug therapy , Pain, Postoperative/chemically induced , Pregabalin/therapeutic use , Tooth Extraction/adverse effects , Tooth, Impacted/surgery , Tooth, Impacted/complications , Double-Blind Method
13.
Int J Biol Macromol ; 252: 126464, 2023 Dec 01.
Article in English | MEDLINE | ID: mdl-37619682

ABSTRACT

Current study reports the combined technique of microneedle array patches and thermoresponsive gels. Microneedles array patch mediated insitu skin depots were evaluated for sustain drug delivery using sodium alginate/Poly (vinylcaprolactam) thermoresponsive gels. Their phase transition property from sol-gel state was monitored with AR2000 rheometer. Ibuprofen sodium was loaded in optimized formulations. The non-soluble cross-linked microneedle array patches (MAPs) were prepared from variable biocompatible polymers using silicone micromoulds. The fabricated MAPs were evaluated for mechanical stability, inskin dissolution, insertion forces and moisture contents. The penetration depth of MAPs in neonatal rabbit skin was tracked by optical coherence tomography. The optimized MAPs (GP10000) were used as microporation source in skin owing to their stable nature. Pores formation in skin samples after MAPs treatment was confirmed by optical coherence tomography, dye binding and skin integrity analysis. The invitro permeation of Ibuprofen sodium from formulations was studied using Franz cells across intact skin and MAPs applied skin. It was concluded from the results that Ibuprofen sodium permeation was observed for longer time through MAPs treated skin as compared to intact skin. Confocal study confirmed the diffusion of drug loaded formulations in deeper tissues with higher intensity.


Subject(s)
Alginates , Ibuprofen , Animals , Rabbits , Ibuprofen/pharmacology , Alginates/chemistry , Administration, Cutaneous , Drug Delivery Systems/methods , Gels , Sodium , Transdermal Patch
14.
Food Chem Toxicol ; 178: 113926, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37406757

ABSTRACT

BACKGROUND AND OBJECTIVE: Ibuprofen, a common non-steroidal anti-inflammatory drug, is used clinically for pain relief and antipyretic treatment worldwide. However, regular or long-term use of ibuprofen may lead to a series of adverse reactions, including gastrointestinal bleeding, hypertension and kidney injury. Previous studies have shown that CYP2C9 gene polymorphism plays an important role in the elimination of various drugs, which leads to the variation in drug efficacy. This study aimed to evaluate the effect of 38 CYP2C9 genotypes on ibuprofen metabolism. METHODS: Thirty-eight recombinant human CYP2C9 microsomal enzymes were obtained using a frugiperda 21 insect expression system according to a previously described method. Assessment of the catalytic function of these variants was completed via a mature incubation system: 5 pmol CYP2C9*1 and 38 CYP2C9 variants recombinant human microsomes, 5 µL cytochrome B5, ibuprofen (5-1000 µM), and Tris-HCl buffer (pH 7.4). The ibuprofen metabolite contents were determined using HPLC analysis. HPLC analysis included a UV detector, Plus-C18 column, and mobile phase [50% acetonitrile and 50% water (containing 0.05% trifluoroacetic acid)]. The kinetic parameters of the CYP2C9 genotypes were obtained by Michaelis-Menten curve fitting. RESULTS: The intrinsic clearance (CLint) of eight variants was not significantly different from CYP2C9*1; four CYP2C9 variants (CYP2C9*38, *44, *53 and *59) showed significantly higher CLint (increase by 35%-230%) than that of the wild-type; the remaining twenty-six variants exhibited significantly reduced CLint (reduced by 30%-99%) compared to that of the wild-type. CONCLUSION: This is the first systematic evaluation of the catalytic characteristics of 38 CYP2C9 genotypes involved ibuprofen metabolism. Our results provide a corresponding supplement to studies on CYP2C9 gene polymorphisms and kinetic characteristics of different variants. We need to focus on poor metabolizers (PMs) with severely abnormal metabolic functions, because they are more susceptible to drug exposure.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal , Ibuprofen , Humans , Ibuprofen/chemistry , Cytochrome P-450 CYP2C9/genetics , Cytochrome P-450 CYP2C9/metabolism , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Polymorphism, Genetic , Genotype
15.
Chemosphere ; 338: 139521, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37482319

ABSTRACT

Aquatic species are continuously exposed to pharmaceuticals and changeable water conditions simultaneously, which can induce changes in the toxicity of pollutants. Cyanobacterium are an organism for which less ecotoxicological tests have been performed compared to green algae. In this study, we decided to check how selected non-steroidal anti-inflammatory drugs (NSAID) affect the grow of Synechocystis salina, picocyanobacterium isolated from the Baltic Sea, with salinity as potential modulator of toxicity. S. salina was exposed to diclofenac (DCF), ibuprofen (IBF) and naproxen (NPX) (nominal 100 mg L-1) in BG11 medium and sea salt supplemented BG11 medium (38 PSU) over 96 h in continuous light at 23 °C. No acute toxicity was found in both tested salinity levels. The comparable grow rate in exposed culture compared to control culture over 4 days indicate lack of stress for several generations which need to be overcome with substantial energy consumption. S. salina was found to be halotolerant and can be species for ecotoxicology test where salinity in an additional stressor. Furthermore, resistant of S. salina to target NSAIDs provide a competitive advantage over other phytoplankton species.


Subject(s)
Ibuprofen , Water Pollutants, Chemical , Ibuprofen/toxicity , Naproxen/toxicity , Diclofenac/toxicity , Salinity , Anti-Inflammatory Agents, Non-Steroidal/toxicity , Water Pollutants, Chemical/toxicity
16.
Trials ; 24(1): 435, 2023 Jun 28.
Article in English | MEDLINE | ID: mdl-37370174

ABSTRACT

BACKGROUND: The duration and regimen of tuberculosis (TB) treatment is currently based predominantly on whether the M. tuberculosis (Mtb) strain is drug-sensitive (DS) or multidrug-resistant (MDR) with doses adjusted by patients' weight only. The systematic stratification of patients for personalized treatment does not exist for TB. As each TB case is different, individualized treatment regimens should be applied to obtain better outcomes. In this scenario, novel therapeutic approaches are urgently needed to (1) improve outcomes and (2) shorten treatment duration, and host-directed therapies (HDT) might be the best solution. Within HDT, repurposed drugs represent a shortcut in drug development and can be implemented at the short term. As hyperinflammation is associated with worse outcomes, HDT with an anti-inflammatory effect might improve outcomes by reducing tissue damage and thus the risk of permanent sequelae. METHODS: SMA-TB is a multicentre randomized, phase IIB, placebo-controlled, three-arm, double-blinded clinical trial (CT) that has been designed in the context of the EC-funded SMA-TB Project ( www.smatb.eu ) in which we propose to use 2 common non-steroidal anti-inflammatory drugs (NSAID), acetylsalicylic acid (ASA) and ibuprofen (Ibu), as an HDT for use as adjunct therapy added to, and compared with, the standard of care (SoC) World Health Organization (WHO)-recommended TB regimen in TB patients. A total of 354 South African and Georgian adults diagnosed with confirmed pulmonary TB will be randomized into SoC TB treatment + placebo, SoC + acetylsalicylic acid or SoC + ibuprofen. DISCUSSION: SMA-TB will provide proof of concept of the HDT as a co-adjuvant treatment and identify the suitability of the intervention for different population groups (different epidemiological settings and drug susceptibility) in the reduction of tissue damage and risk of bad outcomes for TB patients. This regimen potentially will be more effective and targeted: organ saving, reducing tissue damage and thereby decreasing the length of treatment and sequelae, increasing cure rates and pathogen clearance and decreasing transmission rates. It will result in better clinical practice, care management and increased well-being of TB patients. TRIAL REGISTRATION: Clinicaltrials.gov NCT04575519. Registered on October 5, 2020.


Subject(s)
Mycobacterium tuberculosis , Tuberculosis, Pulmonary , Adult , Humans , Anti-Inflammatory Agents/therapeutic use , Antitubercular Agents/adverse effects , Aspirin/adverse effects , Ibuprofen/adverse effects , Multicenter Studies as Topic , Randomized Controlled Trials as Topic , Treatment Outcome , Tuberculosis, Pulmonary/diagnosis , World Health Organization , Clinical Trials, Phase II as Topic
17.
Environ Res ; 231(Pt 3): 116223, 2023 08 15.
Article in English | MEDLINE | ID: mdl-37245577

ABSTRACT

Pharmaceuticals in water are a growing environmental concern, as they can harm aquatic life and human health. To address this issue, an adsorbent made from coffee waste that effectively removes ibuprofen (a common pharmaceutical pollutant) from wastewater was developed. The experimental adsorption phase was planned using a Design of Experiments approach with Box-Behnken strategy. The relation between the ibuprofen removal efficiency and various independent variables, including adsorbent weight (0.01-0.1 g) and pH (3-9), was evaluated via a regression model with 3-level and 4-factors using the Response surface methodology (RSM) . The optimal ibuprofen removal was achieved after 15 min using 0.1 g adsorbent at 32.4 °C and pH = 6.9. Moreover, the process was optimized using two powerful bio-inspired metaheuristics (Bacterial Foraging Optimization and Virus Optimization Algorithm). The adsorption kinetics, equilibrium, and thermodynamics of ibuprofen onto waste coffee-derived activated carbon were modeled at the identified optimal conditions. The Langmuir and Freundlich adsorption isotherms were implemented to investigate adsorption equilibrium, and thermodynamic parameters were also calculated. According to the Langmuir isotherm model, the adsorbent's maximum adsorption capacity was 350.00 mg g-1 at 35 °C. The findings revealed that the ibuprofen adsorption was well-matched with the Freundlich isotherm model, indicating multilayer adsorption on heterogeneous sites. The computed positive enthalpy value showed the endothermic nature of ibuprofen adsorption at the adsorbate interface.


Subject(s)
Coffee , Water Pollutants, Chemical , Humans , Ibuprofen , Adsorption , Kinetics , Water Pollutants, Chemical/analysis , Thermodynamics , Hydrogen-Ion Concentration
18.
Sci Rep ; 13(1): 6642, 2023 04 24.
Article in English | MEDLINE | ID: mdl-37095163

ABSTRACT

Chronic inflammatory temporomandibular disorder (TMD) pain has a high prevalence, and available nonspecific treatments have adverse side effects. ECa 233, a standardized Centella asiatica extract, is highly anti-inflammatory and safe. We investigated its therapeutic effects by injecting complete Freund's adjuvant (CFA) into right temporomandibular joint of mice and administering either ibuprofen or ECa 233 (30, 100, and 300 mg/kg) for 28 days. Inflammatory and nociceptive markers, bone density, and pain hypersensitivity were examined. CFA decreased ipsilateral bone density, suggesting inflammation localization, which ipsilaterally caused immediate calcitonin gene-related peptide elevation in the trigeminal ganglia (TG) and trigeminal subnucleus caudalis (TNC), followed by late increase of NaV1.7 in TG and of p-CREB and activation of microglia in TNC. Contralaterally, only p-CREB and activated microglia in TNC showed delayed increase. Pain hypersensitivity, which developed early ipsilaterally, but late contralaterally, was reduced by ibuprofen and ECa 233 (30 or 100 mg/kg). However, ibuprofen and only 100-mg/kg ECa 233 effectively mitigated marker elevation. This suggests 30-mg/kg ECa 233 was antinociceptive, whereas 100-mg/kg ECa 233 was both anti-inflammatory and antinociceptive. ECa 233 may be alternatively and safely used for treating chronic inflammatory TMD pain, showing an inverted U-shaped dose-response relationship with maximal effect at 100 mg/kg.


Subject(s)
Centella , Hypersensitivity , Temporomandibular Joint Disorders , Animals , Male , Ibuprofen , Pain , Freund's Adjuvant , Disease Models, Animal , Analgesics
19.
J Mol Recognit ; 36(7): e3015, 2023 07.
Article in English | MEDLINE | ID: mdl-37021769

ABSTRACT

Recent interest has focused on the biosynthesis of metal nanoparticles (NPs), particularly from plants. The production of precipitate served as an early indicator of the presence in the present study's use of ZnO NPs green synthesis of these particles, which was further validated by; Fourier transform infrared spectroscopy, x-ray diffraction. Additionally, the Brunauer-Emmett-Teller was used to calculate the surface area, which came out to be 119.12 m2 /g. Since the true effects of new pollutants, including medicines, on the environment and human health are not well understood, their presence in aquatic systems poses a severe hazard. For this reason, the antibiotic Ibuprofen (IBP) was absorbable to ZnO-NPs in this search. As opposed to fitting to Langmuir isothermally, the adsorption process was discovered to be pseudo-second-order kinetically, and the reaction was determined to be a chemisorption process. The process was endothermic and spontaneous, according to thermodynamic studies. Maximizing IBP removal from aqueous solution required the use of a Box-Behnken surface statistical design with four components, four levels, and response surface modeling. Solution pH, IBP concentration, duration, and dose were the four parameters that were utilized. The regeneration process, which is employed for five cycles with excellent efficiency, is the best benefit of using ZnO-NPs. Examine the elimination of pollutants from actual samples as well. However, the adsorbent is quite effective at reducing biological activity. At high concentrations of ZnO-NPs demonstrated notable antioxidant activity and Red Blood Cell (RBC) hemocompatibility and no discernible hemolysis was seen. ZnO-NPs demonstrated a notable percent suppression of α-amylase up to 53.6% at 400 µg/mL, and so displayed potential as an antidiabetic. Cyclooxygenase was suppressed by ZnO-NPs in an anti-inflammatory test (COX-1 & COX-2) up to 56.32% and 52.04% at a concentration of 400 µg/mL, respectively. Significant anti-Alzheimer potential was demonstrated by ZnO-NPs at 400 µg/mL by inhibiting Acetyl cholinesterase and Butyl cholinesterase up to 68.98 ± 1.62% and 62.36%, respectively. We concluded that guava extract is helpful for ZnO-NP reduction and capping. The bioengineered NPs could prevent Alzheimer's, diabetes, and inflammation and were biocompatible.


Subject(s)
Metal Nanoparticles , Nanoparticles , Zinc Oxide , Humans , Zinc Oxide/chemistry , Zinc Oxide/pharmacology , Ibuprofen , Adsorption , Nanoparticles/chemistry , Metal Nanoparticles/chemistry , Anti-Bacterial Agents/pharmacology , Pharmaceutical Preparations , Spectroscopy, Fourier Transform Infrared , Plant Extracts/chemistry
20.
Anesth Analg ; 136(6): 1122-1132, 2023 06 01.
Article in English | MEDLINE | ID: mdl-37043404

ABSTRACT

BACKGROUND: Most of the 1.1 million women who deliver by cesarean in the United States each year have an uncomplicated recovery. However, severe pain resistant to standard multimodal therapy within the first days after surgery is associated with an increased risk for prolonged pain and opioid use. The best outpatient management for parturients with severe resistant early onset pain is not known. METHODS: We performed a prospective, double-blind, placebo-controlled, randomized trial of up to 12 weeks of outpatient treatment with gabapentin to evaluate its effectiveness to facilitate opioid cessation in women with at least 2 reports of severe pain during the immediate postpartum period resistant to standard multimodal pain management. Time to opioid cessation was the primary outcome. Time to pain resolution; time to discontinuation of gabapentin, acetaminophen, and ibuprofen; time to self-reported recovery; and National Institute of Health Patient-Reported Outcomes System (PROMIS) surveys for anxiety, depression, fatigue, and physical function were assessed as secondary outcomes. RESULTS: There was no difference in time to opioid cessation between patients who were randomly assigned to be treated with gabapentin (Kaplan-Meier estimated median of 2 [25th-75th percentiles of 1-3] weeks, n = 35) versus those who were treated with placebo (2 [1-3] weeks, n = 35). The hazard ratio was 1.1 (95% confidence interval [CI], 0.67-1.8), P = .65. There were no differences in any secondary end points between the study groups. CONCLUSIONS: Outpatient supplementation with gabapentin did not reduce time to opioid cessation, pain, anxiety, depression, fatigue, or improve physical function in women with severe pain after cesarean delivery. Gabapentin should not be routinely added to the standard outpatient multimodal regimen of ibuprofen, acetaminophen, and opioids.


Subject(s)
Acute Pain , Analgesics, Opioid , Pregnancy , Humans , Female , Gabapentin , Acetaminophen , Acute Pain/diagnosis , Acute Pain/drug therapy , Acute Pain/etiology , Ibuprofen , Outpatients , Prospective Studies , Pain, Postoperative/diagnosis , Pain, Postoperative/drug therapy , Pain, Postoperative/etiology , Double-Blind Method
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