Administration Of Nonsteroidal Anti-inflammatory Drugs Research Articles

Chronological effects of non-steroidal anti-inflammatory drug therapy on oxidative stress and antioxidant status in patients with rheumatoid arthritis

Non-steroidal anti-inflammatory drugs (NSAIDs) are effective in reducing pain and inflammation in rheumatoid arthritis and other joint- and muscle-associated diseases. However, the extensive, long-term, and over the counter administration of NSAIDs may cause various side effects in the patients. In the present study, the chronological effect of NSAIDs on oxidative stress and antioxidant status in patients with rheumatoid arthritis was studied. The study included 100 female individuals categorized in four major groups: (1) control group consisting of age- and gender-matched healthy individuals, (2) NRA-NSAID individuals taking NSAIDs without any history of RA, (3) RA individuals with a history of RA but not taking NSAIDs, and (4) RA-NSAID individuals with chronic RA and taking NSAIDs for a long period. The sera of the participants were analyzed for the oxidative stress and antioxidant status. The RA-NSAID group showed the significantly highest oxidative stress, in terms of malondialdehyde content and lipid-reducing ability as determined in thiocyanate and hemoglobin-induced linoleic acid systems. However, the free radical scavenging ability of the RA-NSAID group, against 2,2-diphenyl-1-picrylhydrazyl, hydroxyl, superoxide, and 2,2-azino-bis-tetrazolium sulfate radicals, was found to be lower than those of the other study groups. The regression analysis of the experimental data showed a significant positive relationship between duration of NSAID intake and malondialdehyde production, lipid-reducing ability, and metal chelating ability in the RA-NSAID patients. The free radical scavenging abilities of the RA-NSAID group were negatively correlated with the duration of NSAID intake. The prolonged use of NSAIDs significantly increased the oxidative stress and decrease the antioxidant potential of both the RA patients and NRA individuals. The study provides awareness to the public particularly the RA patients regarding the risk of oxidative stress-associated abnormalities caused by the frequent and prolonged use of NSAIDs for temporary relief from pain. Key Points • The study presents the effects of long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) on antioxidant status of patients with rheumatoid arthritis. • The continuous administration of NSAIDs has been found to significantly increase the oxidative stress of the patients with rheumatoid arthritis as well as the individuals with no signs of rheumatoid arthritis. • The prolonged NSAID therapy also decreased the antioxidant potential of the patients with rheumatoid arthritis as well as the individuals with no signs of rheumatoid arthritis. • The study would be a significant and valuable contribution to the literature for the awareness regarding the use of NSAIDs.

Chronic use of statins and acetylsalicylic acid and incidence of post-endoscopic retrograde cholangiopancreatography acute pancreatitis: A multicenter, prospective, cohort study.

Post-endoscopic retrograde cholangiopancreatography (ERCP) acute pancreatitis (PEP) is a frequent complication of this endoscopic procedure. Chronic statin intake has been linked to lower incidence and severity of acute pancreatitis (AP). Periprocedural rectal administration of non-steroidal anti-inflammatory drugs is protective against PEP, but the role of chronic acetylsalicylic acid (ASA) treatment is unclear. We aimed to investigate whether statins and chronic ASA intake are associated with lower risk of PEP. An international, multicenter, prospective cohort study. Consecutive patients undergoing ERCP in seven European centers were included. Patients were followed-up to detect those with PEP. Multivariate analysis by means of binary logistic regression was performed, and adjusted odds ratios (aORs) were calculated. A total of 1150 patients were included, and 70 (6.1%) patients developed PEP. Among statins users, 8.1% developed PEP vs. 5.4% among non-users (P=0.09). Multivariate analysis showed no association between statin use and PEP incidence (aOR 1.68 (95% CI 0.94-2.99, P=0.08)). Statin use had no effect on severity of PEP, being mild in 92.0% of statin users vs. 82.2% in non-statin users (P=0.31). Chronic ASA use was not associated with PEP either (aOR 1.02 (95% CI 0.49-2.13), P=0.96). Abuse of alcohol and previous endoscopic biliary sphincterotomy were protective factors against PEP, while >1 pancreatic guidewire passage, normal bilirubin values, and duration of the procedure >20minutes, were risk factors. The use of statins or ASA is not associated with a lower risk or a milder course of PEP.

Histopathological aspects of co-administration of dexamethasone and diclofenac sodium on male albino rats

Background and objective: Treatment of an animal with dexamethasone will result in sinuses extension, fat accumulation in the liver, and enlargement of hepatocytes. Whereas, non-steroidal anti-inflammatory drugs (diclofenac sodium) administration may lead to degeneration and formation of wide areas in the form of sinusoidal. Hydropic degeneration possibly is seen in the tubular epithelial cells of the kidney tissue. This study aimed to assess the toxic and side effects of dexamethasone and diclofenac sodium on the liver and kidney in rats, whether used separately or together. Methods: A total of 40 male albino rats were divided into four groups of ten in each, including the control group. One set was treated with dexamethasone (1.6 mg/kg/day), the other was treated with diclofenac sodium (30 mg /kg/day), and the last was treated with both drugs together at the same dose without mixture. Both drugs were administered intramuscularly for 30 days. Sections from the liver and kidney were stained by Hematoxeline and Eosin, then examined under a microscope. Results: Histopathological variation in the liver and kidney tissue of the treated animals have revealed that each drug (dexamethasone, diclofenac sodium) showed a significant alteration. Strong changes (+ + +) were observed in kidney tissue include degeneration, inflammatory aggregation, fibrosis, and edema, whereas in liver showed central vein dilatation, necrosis, and kupffer cells hyperplasia. Treating with the two drugs together, less alteration (+) in the tissues was noticed. Conclusion: The effect of both used drugs (dexamethasone and diclofenac sodium) was observed on the liver and kidney tissues of the experimental animals (rats) regardless of being applied separately or the two together. A probable inhibition role of the two drugs on each other have been noticed that lead to call for more detail investigation on this matter in years to come.

Features of management of patientswith NSAID-induced gastropathy: from understanding the mechanisms of development to the strategy of prevention and treatment. Risks of short-term use of non-steroidal anti-inflammatory drugs. Part I

Nonsteroidal anti‑inflammatory drugs (NSAIDs) is a big group of medications with different chemical structure but common mechanisms of pharmacological actions and ability to provide analgesic, anti‑inflammatory and antipyretic effects. NSAIDs is one of the therapeutically instruments to relief acute and chronic pain at a wide spectrum of diseases and pathological conditions. NSAIDs administration is an integral part of the work of physicians, rheumatologists, neurologists, anesthesiologists, surgeons, traumatologists, gynecologists and other medical specialties. NSAIDs are effective and easy to use, but they can cause serious complications and first of all, the gastrointestinal adverse events.The paper present analysis of the structure of drug‑induced injuries of upper gastrointestinal tract in patients taking NSAIDs. The risks of adverse events that develop against the background of short‑term NSAIDs use for analgesic, anti‑inflammatory, antipyretic purposes have been discussed. The data on the frequency and features of clinical, endoscopic and morphological manifestations of NSAID‑gastropathies are presented. The danger of these complications, which may be accompanied by life‑threatening conditions such as bleeding or perforation, has been demonstrated. The role of modern endoscopic methods for the diagnosis of NSAID‑gastropathies is evaluated. Based on a clinical example, the authors proposed a strategy for the prevention and treatment of NSAID‑gastropathy, which arose against the background of asymptomatic Helicobacter pylori infection. Current data on various strategies for the treatment and prevention of NSAID gastropathies are presented. Based on the analysis, it has been concluded that the use of proton pump inhibitors (PPIs) and the eradication of Helicobacter pylori infection are the best strategies. The use of double doses of PPIs makes it possible to increase the effectiveness of prevention and treatment of NSAID‑gastropathies, as well as eradication therapy.

Retrospective evaluation of acute kidney injury in dogs with pit viper envenomation (2008-2017): 56 cases.

To describe the clinicopathological characteristics of dogs that develop acute kidney injury (AKI) secondary to pit viper envenomation, and to describe the association between development of AKI and clinical course and outcome. Retrospective study. University teaching hospital. Client-owned dogs treated with at least 1 vial of antivenom following pit viper envenomation and that had at least 2 plasma creatinine concentrations measured during the course of hospitalization. None. Sixty-three dogs met the inclusion criteria. One was excluded due chronic kidney disease, and 6 were excluded due to nonsteroidal anti-inflammatory drug administration. Of the 56 dogs included in the study, 16 developed AKI (29%). Dogs with AKI received a significantly higher dose of antivenom, 8.7 ± 6.8 total vials versus dogs in the non-AKI group that received 4.2 ± 2.6 vials (P=0.006). Dogs in the AKI group were significantly more tachycardic (P=0.028), hypotensive (P=0.002), had a higher shock index (P=0.012), and were more likely to receive transfusions with packed red blood cells (P=0.042) than dogs in the non-AKI group. No significant association was identified between the development of AKI and length of hospitalization. The only factors that were significantly associated with degree of severity of AKI included the receipt of blood transfusion (P=0.006) and number of vials of antivenom administered (P=0.03). The development of AKI was significantly associated with outcome (P<0.001), with 5 of 16 (31%) dogs in the AKI group surviving to discharge, 7 of 16 (44%) dying, and 4 of 16 (25%) being euthanized versus 39 of 40 (98%) surviving to discharge in the non-AKI group and 1 of 40 (2%) dying in hospital. Development of AKI in dogs following pit viper envenomation carries an increased risk of mortality that is associated with severity of shock at presentation and increased doses of antivenom administration.

Safety of non-steroidal anti-inflammatory drugs in postpartum period in women with hypertensive disorders of pregnancy: systematic review and meta-analysis.

To assess the effect of non-steroidal anti-inflammatory drugs (NSAIDs) on blood pressure when administered for postpartum analgesia in women with hypertensive disorders of pregnancy. MEDLINE, Scopus, CENTRAL, Clinicaltrials.gov and Google Scholar databases were searched systematically from inception to 5 December 2019 for studies evaluating the safety of postpartum NSAIDs in women with any gestational hypertensive disorder. Randomized controlled trials (RCTs) and cohort studies were eligible for inclusion. Case-control studies, case series and case reports were excluded. The primary outcomes of interest were the incidence of severe hypertension and systolic, diastolic and mean arterial blood pressure. Pooled estimates were obtained by fitting a random-effects statistical model. The quality of evidence was assessed according to Grading of Recommendations, Assessment, Development and Evaluations (GRADE) guidelines. Ten studies were included, comprising five RCTs and five retrospective cohort studies and involving a total of 1647 women. All studies were evaluated qualitatively and eight of them were included in the quantitative meta-analysis. Administration of NSAIDs was not associated with a significantly higher risk of severe postpartum hypertension (odds ratio, 1.52 (95% CI, 0.77-3.01)). Similarly, no significant differences were found in postpartum systolic blood pressure (mean difference (MD), -3.03 mmHg (95% CI, -6.21 to 0.15 mmHg)) and mean arterial pressure (MD, -0.38 mmHg (95% CI, -1.88 to 1.11 mmHg)) between women who received NSAIDs and those who did not, whereas postpartum diastolic blood pressure was marginally lower in women treated with NSAIDs (MD, -2.28 mmHg (95% CI, -4.44 to -0.13 mmHg)). The same effects were observed when studies with a large sample size, RCTs, women with severe pre-eclampsia and studies using ibuprofen as the study drug and acetaminophen as the control treatment were examined separately. The credibility of evidence was judged to be very low according to GRADE, owing to concerns about study limitations, inconsistency and imprecision. This meta-analysis suggests that postpartum administration of NSAIDs is not associated with elevated blood pressure in women with hypertensive disorders of pregnancy. However, the existing evidence is of very low quality, thus future large-scale RCTs are warranted to verify the safety of postpartum NSAIDs in this population. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Adverse reactions with the use of non-steroidal anti-inflammatory drugs

Non-steroidal anti-inflammatory drugs (NSAIDs) are included in a pharmacological group of drugs with different chemical structures providing anti-inflammatory, analgesic and antipyretic actions, as well as antiplatelet action to a certain degree. Unfortunately, NSAIDs can cause a wide range of adverse reactions (AR) posing a serious risk to the health and life of patients. Therefore, the rational use of NSAIDs should include methods for effective prevention of drug complications. Many NSAIDs have a pronounced therapeutic effect, simultaneously causing many undesirable effects, so the drug shall be chosen considering the development of predicted side effects and modern algorithms. According to clinical recommendations, risk factors and administration of safer NSAIDs shall be considered as the main prevention method. Besides, it is possible to protect the patient from the upper gastrointestinal tract complications using proton pump inhibitors. It should be noted that there are no effective medication methods for kidney and liver protection to reduce the risk of NSAID-associated complications.

Analysis of the results of endoscopic examination of the upper git in decompensated OA

Results of fibrogastroduodenoscopy examination of 69 patients with OA of the knee are presented. A long history of non-steroidal anti-inflammatory drugs administration, a high risk of NSAID-associated gastropathy development. The fibrogastroduodenoscopy results of patients with OA showed that 97.1 % of the examined had changes in the upper GIT. The predominance of superficial inflammatory changes was detected but erosive changes in the oesophagus (10.9 %), stomach (29.6 %) and duodenum (14%) were also present.

Marker changes of blood plasma proteinogram in rats with toxic hepatitis

In recent years, there has been a pronounced tendency to increase in the incidence of drug-induced liver damage due to the growing expansion of the pharmaceutical market, which is also observed in the case of incorrect administration of nonsteroidal anti-inflammatory drugs (NSAIDs). In this case, the violation of the functional state of the body has a negative effect on synthetic processes, which in combination with the protein system of tissues significantly affects the metabolic homeostasis of the body. Therefore, the aim of the study was to determine marker changes in the plasma protein spectrum in laboratory rats with diclofenac-induced hepatitis and the effectiveness of reparative therapy based on milk phospholipids. The drug form of toxic hepatitis in laboratory animals was induced according to the author’s model by oral administration of diclofenac sodium (NSAID group) at a dose of 12.5 mg/kg, once a day for 14 days. Thus, in rats with toxic hepatitis there was a probable decrease in plasma total protein content by 15.6% compared with control, indicating a violation of protein-synthesizing function of the liver. With the introduction into the body of clinically healthy and sick animals of the liposomal form of the bioadditive "FLP-MD" based on milk phospholipids, the level of total protein in blood plasma corresponded to control values. As a result of the study of the plasma protein spectrum of Wistar rats, the four most sensitive indicators, which undergo significant probable changes in absolute and relative units of measurement with the development of toxic diclofenac-induced hepatitis, are protein fractions with molecular weights of 180–190, 150–170, 60 and 54–58 kDa and four markers of the effectiveness of restoring the protein-synthesizing function of the liver with the use of corrective therapy, in particular, bioadditives "FLP-MD" – 900, 180–190, 68–70 kDa and the value of A/G ratio, which is important for implementation in applied veterinary medicine, especially in the diagnosis of NSAID hepatopathy, supplementing the picture of its pathogenesis at the molecular level and testing the effectiveness of newly created drugs of hepatoprotective profile.

Clinical Control of CSU with Antihistamines Allows for Tolerance of NSAID-Exacerbated Cutaneous Disease

Many patients with chronic spontaneous urticaria (CSU) experience exacerbations after the administration of nonsteroidal anti-inflammatory drugs (NSAIDs), with clinical implications for the selection of therapeutic options for pain management. Case reports suggest that antihistamines could prevent these reactions. To determine whether antihistamines can prevent NSAID-exacerbated reactions in patients with CSU. Data on 121 patients with CSU and a history of NSAID exacerbations were evaluated. Two types of challenge with NSAIDs were performed using the NSAIDs reported in the medical record (a diagnostic challenge test without the use of antihistamines and a challenge test using antihistamines). The order in which the tests were performed in each patient was dependent on the treating physician. Patients with a positive first diagnostic challenge underwent a second challenge using H1-antihistamines (anti-H1), patients with a negative first challenge using anti-H1 underwent a second diagnostic challenge without the use of anti-H1, and patients with a negative first diagnostic challenge or a positive first challenge using anti-H1 did not undergo a second challenge. In some patients, additional challenges were performed with an alternative NSAID before performing the diagnostic challenge test or the challenge test using anti-H1. In the diagnostic challenge test, 96 patients tested positive. Seventy-two (75%) of these patients tolerated the NSAIDs involved in the reaction when they used antihistamines. NSAID restrictions create many inconveniences for patients with CSU. Clinical control of CSU with the use of antihistamines can prevent further exacerbations due to NSAID intake in many patients to help them avoid unnecessary restrictions.

Do early non-steroidal anti-inflammatory drugs for analgesia worsen acute kidney injury in critically ill trauma patients? An inverse probability of treatment weighted analysis.

Administration of nonsteroidal anti-inflammatory drugs (NSAIDs) for acute posttraumatic analgesia is increasing in popularity as an alternative to opioids despite reservations regarding its potential impact on the development of acute kidney injury (AKI). We hypothesized that early NSAID administration for analgesia would be associated with worsened renal function in severely injured trauma patients. A retrospective cohort study of severely injured adult (≥16 years) patients admitted to the intensive care unit with ≥1 rib fracture between 2010 and 2017 was performed. The early NSAID group was defined by receipt of one or more doses of NSAID within the first 48 hours of hospitalization. Acute kidney injury diagnosis and staging were defined by the Kidney Disease Improving Global Outcomes Guidelines. The primary outcome was a composite measure of two outcomes within the first week of hospitalization: (1) AKI progression (increase in AKI stage from arrival) or (2) death. Secondary outcomes included AKI progression, AKI improvement, AKI duration, and mortality. Inverse propensity of treatment weights were generated using clinically sound covariates suspected to be associated with the decision to give early NSAIDs and the primary or secondary outcomes. Multivariable analyses were performed adjusting for inverse propensity of treatment weights, covariates, and length of stay. Of 2,340 patients, 268 (11%) were administered early NSAIDs. When compared with the control group, patients who received early NSAIDs were less severely injured. Renal outcomes were worse in the control group. Standardized mean differences were minimal after weighting. On multivariable analysis, administration of early NSAIDs was not associated with worsened renal outcomes or increased mortality. Although only 11% of patients received early NSAIDs after trauma for analgesia, early NSAID exposure was not associated with increased AKI progression, decreased AKI improvement, prolonged duration, or increased mortality. Given the lack of evidence showing harm, early NSAIDs for analgesia may be underused for severely injured patients. Prognostic, level III, Therapeutic, level IV.

Optimized Ellagic Acid-Ca Pectinate Floating Beads for Gastroprotection against Indomethacin-Induced Gastric Injury in Rats.

A peptic ulcer is an alimentary tract injury that leads to a mucosal defect reaching the submucosa. This work aimed to optimize and maximize ellagic acid (EA) loading in Ca pectinate floating beads to maximize the release for 24 h. Three factors were selected: Ca pectinate concentration (X1, 1–3 w/v %), EA concentration (X2, 1–3 w/v %) and the dropping time (X3, 10–30 min). The factorial design proposed eight formulations. The optimized EA–Ca pectinate formulation was evaluated for the gastric ulcer index and the oxidative stress parameter determination of gastric mucosa. The results indicated that the optimum EA–Ca pectinate formula significantly improved the gastric ulcer index in comparison with raw EA. The protective effect of the optimized EA–Ca pectinate formula was further indicated by the histopathological features of the stomach. The results of the study indicate that an EA formulation in the form of Ca pectinate beads would be effective for protection against gastric ulcers because of Nonsteroidal anti-inflammatory drugs (NSAID) administration.

Nicolau syndrome caused by non-steroidal anti-inflammatory drugs: Systematic literature review.

Intramuscular or, more rarely, local drug injection is occasionally followed by immediate local pain, livedoid skin lesions and, some days later, the development of ischemic lesions. This very uncommon but potentially severe reaction, termed Nicolau syndrome, is traditionally associated with bismuth and β-lactam antimicrobials. The aim of this report was to review the literature associating Nicolau syndrome with the administration of non-steroidal anti-inflammatory drugs. The National Library, Excerpta Medica, Web of Science and Cochrane library databases were used. Sixty-two cases (40 females and 22 males aged from 13 to 81, median 57years) of Nicolau syndrome were published after 1992. Fifty-three cases occurred after diclofenac. The remaining nine cases were associated with ketoprofen (N=2), ketorolac (N=2), phenylbutazone (N=2), etofenamate (N=1), ibuprofen (N=1) and piroxicam (N=1). Although Nicolau syndrome is extremely uncommon, physicians must be aware of this complication after intramuscular administration of non-steroidal anti-inflammatory drugs and should avoid unnecessary injections.

Bilateral Total Knee Arthroplasty and In-Hospital Opioid Dispension: A Population-Based Study

BackgroundThere is paucity of data regarding opioid dispension in patients undergoing bilateral total knee arthroplasty (BTKA). Our aim is to compare in-hospital opioid dispension between BTKA and unilateral TKA (UTKA) and to identify other factors associated with opioid dispension in the BTKA and UTKA cohorts. MethodsPatients receiving elective TKA from 2006 to 2016 were retrospectively extracted from the Premier Healthcare Database. The effect of interest was bilateral TKA. Our primary outcome was in-hospital opioid dispension in oral morphine equivalents. Univariable statistics between study variables and TKA type were obtained. A multilevel logistic regression model was run for the outcome of high opioid dispension. ResultsA total of 1,029,120 patients were included. Among these, 14,469 (1.4%) underwent a BTKA. Within the 10-year period studied, there was a decrease in opioid dispension in both groups. Logistic regression analysis showed that patients treated with BTKA had 1.68 times higher odds for high opioid dispension compared to UTKA patients (odds ratio = 1.68; 95.5% confidence interval = 1.62, 1.75; P < .0001). White race, longer length of stay, Charlson/Deyo index, type of insurance, rural location, general anesthesia, peripheral nerve block use, and patient-controlled analgesia were also associated with high opioid dispension. Conversely, a more recent year of surgery, female gender, older age, and administration of nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors were associated with lower odds for high opioid dispension. ConclusionBTKA patients have increased odds for higher in-hospital opioid dispension compared to UTKA recipients. Utilization and prescribing habits should be examined to determine the optimal approach to opioid prescription in BTKA patients compared to UTKA.

In Vivo Evaluation of Effect of Preoperative Ibuprofen on Proinflammatory Mediators in Irreversible Pulpitis Cases

IntroductionPreoperative administration of nonsteroidal anti-inflammatory drugs has been suggested as a method for increasing the efficacy of local anesthetics and decreasing postoperative pain in symptomatic irreversible pulpitis cases. However, the effects of ibuprofen at the molecular level are still unknown. Hence, the purpose of this study was to compare the levels of proinflammatory mediators in the dental pulp of teeth with irreversible pulpitis in patients who medicated with preoperative ibuprofen versus those who did not. MethodsThirty-four patients undergoing conventional endodontic therapy for teeth with irreversible pulpitis were selected and randomly assigned into either the ibuprofen or nonibuprofen group. Four patients undergoing endodontic therapy for prosthodontic reasons served as controls. Patients in the ibuprofen group were instructed to take 600 mg ibuprofen 1 hour before treatment, whereas patients in the nonibuprofen and control groups were asked to avoid analgesics before treatment. Blood samples obtained from the pulp upon access were tested for levels of prostaglandin E2, tumor necrosis efactor alpha, interleukin (IL)-6, IL-1β, and interferon gamma using high-sensitivity enzyme-linked immunosorbent assay. Postoperative pain levels were recorded for the groups. Data for the cytokine levels and postoperative pain were analyzed using statistical analysis. ResultsThere was a significant decrease in the levels of prostaglandin E2, tumor necrosis factor alpha, IL-6, and interferon gamma in the ibuprofen group compared with the nonibuprofen group. No significant differences were noted in the postoperative pain levels between these groups. ConclusionsThe data showed that preoperative ibuprofen significantly decreased the levels of most proinflammatory cytokines in the dental pulp, which could possibly help with anesthesia in irreversible cases.

Combined therapy of pain syndromes: rationale and prospects for potentiation of effects

Pain syndrome accompanies absolute majority of diseases, therefore problems of adequate anesthesia remain acute not only for urgent conditions but also for everyday medical practice. Modern approaches of anesthetic therapy should consider not only pathogenic mechanisms of evolving pain syndrome by a certain patient but also necessity to administer drug combinations. It allows potentiating an analgesic effect, to decrease effective dosages of individual drugs and minimize adverse effects. The administration of non-steroidal anti-inflammatory drugs together with B vitamins and tolperisone is justified in a marked pain syndrome with a spastic component and/or spasms of skeletal muscles, muscle contractures, myofascial pain syndromes, as well in rehabilitation therapy after orthopedic and traumatology surgeries. The article considers pathogenic details of such combined therapy, discloses mechanism of synergic action of the proposed drug combination.

Safety and Efficacy of Topical Diclofenac and Subcutaneous Firocoxib, Ketoprofen, and Meloxicam in Smoky Jungle Frogs (Leptodactylus pentadactylus )

Although nonsteroidal anti-inflammatory drugs (NSAIDs) are often used in anurans, limited pharmacodynamic data are available regarding their value, particularly with regards to repeated dosing. This study investigated the efficacy and safety of serial, once-daily NSAID dosing in smoky jungle frogs (Leptodactylus pentadactylus). Twenty frogs were randomly assigned to receive one of five treatments, once daily for six consecutive days: topical diclofenac (1 mg/kg) or subcutaneous firocoxib (5 mg/kg), ketoprofen (1 mg/kg), meloxicam (0.2 mg/kg), or an equal volume 0.9% saline (control). An acetic acid test was used to determine the nociceptive threshold for each frog 2, 8, 24, 48, and 144 h after initial drug administration. All frogs were euthanized on day 7 for gross examination and histopathology. No significant difference in response was noted for any drug at any time point compared with saline. Mean or median test response for NSAID groups was greater than or equal to saline in 3/4, 2/4, 4/4, 4/4, and 3/4 frogs at 2, 8, 24, 48, and 144 h, respectively. Significant necropsy findings included epidermal necrosis of the hindlimbs in 7/20 frogs (NSAID groups), gastric ulceration in 6/ 20 frogs (NSAID and saline groups), and renal tubular degeneration in 1/20 frogs (NSAID group). None of the aforementioned pathologies were suspected to be secondary to NSAID administration. Further research regarding NSAID pharmacokinetics and pharmacodynamics in anurans is warranted. Topical acetic acid is correlated with epidermal necrosis in smoky jungle frogs.

Low Serum Naproxen Concentrations Are Associated with Minimal Pain Relief: A Preliminary Study in Women with Dysmenorrhea.

Incomplete pain relief after administration of nonsteroidal anti-inflammatory drugs (NSAIDs) is common, but it is unknown whether malabsorption or heightened metabolism contributes to NSAID resistance. To explain the etiology of NSAID resistance, we evaluated naproxen absorption and metabolism in relation to pain relief in a pilot study of women with dysmenorrhea. During menses, participants completed before and after naproxen ingestion pain assessments. Analgesic effectiveness was calculated as a percent change in pain rating before and after naproxen administration. To evaluate the impact of malabsorption, the correlation between analgesic effectiveness and serum naproxen was analyzed. To identify whether hypermetabolism contributes to NSAID resistance, we also analyzed the metabolite O-desmethylnaproxen. Serum naproxen and O-desmethylnaproxen concentrations of the dysmenorrheic cohort (N = 23, 126 ± 10 µg/mL, 381 ± 56 ng/mL) and healthy controls (N = 12, 135 ± 8 µg/mL, 355 ± 58 ng/mL) were not significantly different (P > 0.05), suggesting that menstrual pain does not affect drug absorption and metabolism. However, nine dysmenorrhea participants had levels of analgesic effectiveness <30%. Among dysmenorrheic women, analgesic effectiveness was correlated with serum naproxen (r = 0.49, P = 0.019) and O-desmethylnaproxen (r = 0.45, P = 0.032) concentrations. After controlling for other gynecological diagnoses, a multivariate model analysis confirmed that lower serum naproxen concentrations were associated with reduced pain relief (P = 0.038). Our preliminary findings suggest that poor drug absorption contributes to ineffective pain relief in dysmenorrheic women. Future studies should explore whether malabsorption contributes to NSAID resistance for other pain conditions.

A Review of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) Medications in Dentistry: Uses and Side Effects

Introduction: Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) are the most commonly used as anti-inflammatory drugs because of their ability to cope with aches and pains. Consideration of rational selection of NSAIDs and a basic understanding of the pharmacokinetic and pharmacodynamic features is important. The dentist must assess the risks and benefits of each drug by considering the medical history needs of everyone. Medications must be prescribed in the appropriate dosage to reduce or avoid complications related to NSAIDs. Objective: To review the uses nonsteroidal anti-inflammatory drugs (NSAIDs) in dentistry. Methods: Scientific evidence and clinical cases were drawn from the literature to support this review and information about the use of anti-inflammatory nosteroids in dentistry was collected. Discussion: The use of NSAIDs in dentistry can be done both before the action and after the action. The administration of NSAIDs is based on doses of various NSAIDs. Each type of NSAIDs has advantages for its beneficial actions and side effects. Conclusion: The literature review proves that the use of NSAIDs in the field of dentistry is very broad. Each drug has side effects and work power, each of which is tailored to the needs and systemic conditions of patients who require administration of this drug. The accuracy of the use or administration of NSAIDs is supported by the knowledge and expertise of doctors or dentists.

Platelet-rich Plasma and Mesenchymal Stem Cells Local Infiltration Promote Functional Recovery and Histological Repair of Experimentally Transected Sciatic Nerves in Rats

IntroductionPlatelet-rich plasma (PRP) products and mesenchymal stem cells (MSCs) seem to have a significant potential as neurogenic therapeutic modulator systems. This study aimed to investigate such biological blood derivatives that could enhance nerve regeneration when applied locally in the primary repair of peripheral nerve transection of an experimental rat model.MethodsA total of 42 two-month-old male Wistar rats were divided into three “treatment” groups (control, PRP, and MSCs). All the subjects were operated under anesthesia, and the surgical site was infiltrated with either normal saline, PRP derived from the animal’s peripheral blood, or MSCs derived from the animal’s femoral bone marrow. All three groups were also sub-divided into two sub-groups based on the post-operative administration of Non-steroidal anti-inflammatory drugs (NSAIDs) or not in order to evaluate the effect of NSAIDs on the final outcome. Three months post-surgery, electromyography evaluation of both hind limbs (right operated and left non-operated) was performed. The animals were euthanized, and nerve repair specimens were prepared for histology.ResultsPRP group had a significant effect (p<0.05) on the sciatic nerve repair when compared with the control group, whereas the MSC group had a positive effect but was not statistically significant (p=0.2). The number of counted neural axons at the area distal to the nerve repair site were significantly repetitive (p<0.05) in both the PRP and MSC groups when compared with the control group.ConclusionsBoth PRP and MSCs appear to play an essential role in the enhancement of nerve repair in terms of functionality and histology. MSCs group demonstrated a positive effect, whereas the PRP group showed statistically significant better results.