Traditional Nonsteroidal Anti-inflammatory Drugs Research Articles

Selective Cyclooxygenase-1 Inhibition by P6 and Gastrotoxicity: Preliminary Investigation

Background/Aims: Gastrointestinal damage (GD) is commonly associated with the inhibition of cyclooxygenase (COX)-1, one of the two known COXs, by traditional non-steroidal anti-inflammatory drugs. More recent evidences have proven that GD is caused by the simultaneous inhibition of the two COXs. This study was designed to evaluate the effect of the selective COX-1 inhibition on gastric integrity. Methods: GD was evaluated in male CD1 mice. Drugs were administered by gastric gavage at a dose of 50 mg/kg (injection volume of 100 µl). Control mice received an equal volume of the vehicle (10% ethanol). Each mouse, in groups of at least 6 mice, received one dose/day for 5 days. Results: In Western blot analysis, COX-1 expression levels were found to be significantly reduced in mice treated with 3-(5-chlorofuran-2-yl)-5-methyl-4-phenylisoxazole (P6) in comparison to mice pretreated with aspirin (ASA), which exhibited higher levels of COX-1, thus confirming the high selectivity of P6 towards COX-1 enzyme inhibition. Mucosal sections obtained from ASA-treated mice showed breaks in the epithelial barrier and a marked alteration of foveolae and gastric glands, whereas stomachs isolated from mice sacrificed after 5 days of chronic administration of P6 (at a dose of up to 50 mg/kg/day) showed sporadic transient mucosal hyperemia and did not seem to display any significant gastric damage. Conclusions: The selective COX-1 inhibition by P6 does not cause gastric damage in mice but preserves mucosal integrity.

D-002 (beeswax alcohols): concurrent joint health benefits and gastroprotection.

Nonsteroidal antiinflammatory drugs include the traditional drugs and more selective COX-2 inhibitors. Traditional nonsteroidal antiinflammatory drug use is hampered by their gastrotoxicity, while COX-2-inhibitors increase the cardiovascular risk. The search of safer substances for managing inflammatory conditions is updated, a challenge wherein dual COX/5-LOX inhibitors have a place. This review summarizes the benefits of D-002, a mixture of higher aliphatic beeswax alcohols, on joint health and gastric mucosa. D-002 elicits gastroprotection through a multiple mechanism that involves the increased secretion and improved quality of the gastric mucus, the reduction of hydroxyl radical, lipid peroxidation, protein oxidation, neutrophil infiltration and the increase of antioxidant enzymes on the gastric mucosa. Consistently, D-002 inhibits NSAIDs, ethanol, pylorus-ligation and acetic acid-induced gastric ulceration in rats, and has reduced gastrointestinal symptoms in clinical studies. Early results found that D-002 was effective in the cotton pellet-induced granuloma and carrageenan-induced pleurisy model in rats, lowering pleural leukotriene B4 levels without causing gastrointestinal ulceration. However, D-002 effects on inflammation received little attention for years. Recent data have shown that D-002 inhibited both COX and 5-LOX activities with a greater affinity for 5-LOX and could act as a dual COX/5-LOX inhibitor. This mechanism might explain efficacy in experimental inflammatory and osteoarthritic models as well as clinical efficacy in osteoarthritic patients while supporting the lack of D-002 gastrotoxicity, but not the gastroprotective effects, which appear to be due to multiple mechanisms. In summary oral D-002 intake could help manage inflammatory conditions that impair joint health, while offering gastroprotection.

Drug Interactions of OTC Analgesics-Aspirin: A Review

Nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin is one of the most important medicines required in basic health care system. The possibility of drug interactions with concomitant use of multiple medications is a clinically relevant issue. Many patients are unaware that over-the-counter (OTC) analgesics can cause potentially severe adverse effects when used in combination with other common medications such as anticoagulants, corticosteroids, or antihypertensive agents. Nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin significantly increased risk of upper abdominal gastrointestinal adverse events in patients who take traditional nonsteroidal anti-inflammatory drugs (NSAIDs). This risk is dose dependent and additional increased in patients who take more than one NSAID or use NSAIDs in combination with certain other medications. Some NSAIDs may also alleviate the antiplatelet benefits of aspirin and may increase blood pressure in patients with hypertension. Clinicians should be aware of potential drug interactions with OTC analgesics when prescribing new medications. Additionally, patients should be properly counseled on the appropriate and safe use of OTC analgesics and make sure that they know the benefits as well as the potential risks of both prescription and overthe-counter medications they are taking.

Health Related Quality of Life among Osteoarthritis Patients: A Comparison of Traditional Non-Steroidal Anti-Inflammatory Drugs and Selective COX-2 Inhibitors in the United Arab Emirates Using the SF-36

Objectives: Osteoarthritis (OA) has a dramatic impact on patients’ health related quality of life (HRQoL). Chronic use of analgesics and anti-inflammatory medications for pain management may improve symptoms but on long term may affect HRQoL negatively. The objective of the present study was to compare the impact of two different classes of analgesics, traditional non-steroidal anti-inflammatory drugs (NSAIDs) and selective cyclo-oxygenase-2 (COX-2) inhibitors on HRQoL among osteoarthritis patients using the SF-36 questionnaire. Methods: Clinic based cross-sectional study conducted at Al-Qassimi Hospital, Sharjah, United Arab Emirates (UAE), over a period of six months. Ethical Approval was obtained from the ethics committee at Al-Qassimi Clinical Research Center. Total of 200 osteoarthritis patients fulfilling the inclusion and exclusion criteria were involved in the study. Patients’ demographics were collected from their medical records. The Medical Outcome Study Short-Form 36 (SF-36) questionnaire was used to measure patients’ HRQoL. SF-36 data were scored using health outcomes scoring software 4.5. Results: Mean age of the subjects was 62.19 ± 9.81 years with females constituting 151 (75.5%) of the patients. In general, females scored lower in most of the HRQoL domains compared to males and there was significant difference between the two groups in the mental health (p = 0.005) & mental component (p = 0.042) domains. Compared to selective COX-2 inhibitors, patients on NSAIDs scored higher on all domains of SF-36 except physical functioning. There was significant difference in mental health domain for patients treated with NSAIDs (p = 0.02). Celecoxib was only better than NSAIDs in osteoarthritis patients with more than one musculoskeletal disorders in the domain of bodily pain (p = 0.009). Conclusion: NSAIDs-treated patients did not differ significantly from celecoxib-treated patients in all domains of the SF-36 except for the mental health domain.

The use of nonsteroidal anti-inflammatory drugs in critically ill horses.

To review the physiology of the cyclooxygenase (COX) enzymes with reference to the beneficial effects of nonsteroidal anti-inflammatory drugs (NSAIDs) related to their analgesic and antiendotoxic properties as well as the mechanisms responsible for adverse gastrointestinal, renal, and coagulation effects. Human and veterinary peer reviewed literature NSAIDs are frequently administered to critically ill horses for their analgesic and anti-inflammatory effects. However, NSAIDs have significant side effects principally on the gastrointestinal mucosa and kidneys. These side effects may be exacerbated in critically ill horses if they have gastrointestinal damage or are volume depleted This review provides important information for equine veterinarians and criticalists on the advantages and disadvantages of using traditional NSAIDs and newer equine COX-2 selective NSAIDs for the management of different conditions in critically ill horses.

Clinical implications of prescribing nonsteroidal anti-inflammatory drugs in oral health care—a review

Nonsteroidal anti-inflammatory drugs (NSAIDs), including both the traditional nonselective NSAIDs and the selective cyclooxygenase (COX)-2 inhibitors, are widely used for their anti-inflammatory and analgesic effects. They are routinely prescribed in dental practice for the management of pain and swelling. Their use in treating acute dental pain and chronic orofacial pain, as adjuncts to the treatment of periodontal disease, and to minimize edema following surgical procedures is well documented. However, long-term utilization of nonselective NSAIDs could increase the risk of gastrointestinal symptoms, ranging from mild (e.g., dyspepsia, nausea, or vomiting) to serious gastric problems (e.g., gastric bleeding or perforation). Therefore, selective COX-2 inhibitors have been developed with fewer GI side effects but the recently identified cardiovascular adverse reactions limit their routine use in dental practice. Another major concern for oral physicians is NSAID-induced mucosal lesions and prolongation of bleeding time during invasive dental procedures. This article reviews therapeutic and analgesic uses of NSAIDs in dentistry. The various issues surrounding NSAID-induced adverse reactions and their implications in dentistry are also discussed.

Clinical Disease Pattern and Drug Evaluation of Patients with Seronegative Spondyloarthritis at the Outpatient Department

Objective: There are a number of diseases in the spondyloarthritis (SpA) family. In this study, we evaluated the clinical disease pattern and drug use of outpatient department (OPD) patients with SpA. Methods: During a one-month period, we consecutively enrolled 100 patients with SpA. The diagnosis of ankylosing spondylitis (AS) was based on the modified New York criteria and that of psoriatic arthritis (PsA) followed The ClASsification of Psoriatic ARthritis (CASPAR) criteria. The new Assessment of SpondyloArthritis international Society (ASAS) classification criteria were used for the diagnosis of axial or peripheral SpA. Patients’ demographic characteristics, disease activity and laboratory tests were fully assessed. Medications currently used with the SpA family include non-steroidal anti-inflammatory drugs (NSAIDs) and TNF-α blockers. Results: A total of 100 SpA patients were consecutively enrolled in this short-term OPD survey. The male-to-female ratio of the enrolled patients was about 2:1 (66 males, 34 females). The clinical disease patterns of the 100 patients included 69 AS, 15 PsA, 12 non-radiographic axial SpA and 4 peripheral SpA. Uveitis was the most common extraarticular feature. Patients with positive HLA-B27 had higher Bath Ankylosing Spondylitis Functional Index (BASFI) scores, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores and CRP. Male AS patients seemed to have a higher CRP level and more severe sacroiliitis. AS patients receiving anti-TNFa therapy had significantly higher BASFI and BASDAI scores. AS patients had higher BASFI scores, and erythrocyte sedimentation rate (ESR) and CRP levels but no difference in BASDAI scores when compared to non-radiographic axial SpA patients. In terms of NSAIDs use, 45% of patients took cyclooxygenase-2 (COX-2) inhibitors (celecoxib, etoricoxib), 18% preferential COX-2 inhibitors (meloxicam), 30% nonselective NSAIDs (diclofenac, etodolac, naproxen), and 5% of patients used no NSAIDs. Besides, a higher percentage (33%) of our patients with SpA received regular anti-TNFα therapy (etanercept 17, adalimumab 15, golimumab 1). Conclusion: This OPD survey of Taiwan SpA patients disclosed not a small percentage (16%) of Taiwan SpA patients had either axial or peripheral SpA. The lack of significant difference in the BASDAI between AS and axial SpA suggests anti-TNFα therapy is indicated when traditional NSAIDs fail in axial SpA patients.

How to mechanistically explain the CONDOR study data

Results of the CONDOR study suggest that in osteoarthritis and rheumatoid arthritis patients at elevated risk of gastrointestinal (GI) events, treatment with celecoxib, a cyclooxygenase (COX)-2 selective non-steroidal anti-inflammatory drug (NSAID), demonstrated significantly lower toxicity in the upper and lower (GI) tract when compared to the non-selective NSAID diclofenac plus a proton-pump-inhibitor (PPI), omeprazole. According to current knowledge, traditional NSAIDs (tNSAIDs) as non-selective COX-inhibitors exert their damaging effects on the upper GI tract, largely by reduction of the COX-1 related synthesis of gastro-protective prostaglandins. Thus, the question arises, how NSAIDs do exert their damaging effects especially in the lower GI tract and how to explain the reduced risk of a COX-2 selective inhibitor, celecoxib. Here we hypothesize, that the toxicity of celecoxib on enteral mucosa cells is lower than observed with other NSAIDs, and can be explained COX-independently by typical physicochemical properties of the NSAID substances (e.g., acidic, lipophilic, amphiphilic, surfactant properties). As a consequence these features account for differences in (1) uncoupling effects on mitochondria, (2) effects on cell membrane integrity, and/or (3) formation of “toxic micelles” with bile salts. The evidence for these differences is mainly based on experimental findings. However, several phenomena show differences in extent (e.g., uncoupling effects). The reduced toxicity appears to be rather a substance-specific characteristic. This is an unconditional reason to carry on investigating these phenomena in experimental and large-scale clinical trials.

COX-2 protects against atherosclerosis independently of local vascular prostacyclin: identification of COX-2 associated pathways implicate Rgl1 and lymphocyte networks.

Cyxlo-oxygenase (COX)-2 inhibitors, including traditional nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with increased cardiovascular side effects, including myocardial infarction. We and others have shown that COX-1 and not COX-2 drives vascular prostacyclin in the healthy cardiovascular system, re-opening the question of how COX-2 might regulate cardiovascular health. In diseased, atherosclerotic vessels, the relative contribution of COX-2 to prostacyclin formation is not clear. Here we have used apoE−/−/COX-2−/− mice to show that, whilst COX-2 profoundly limits atherosclerosis, this protection is independent of local prostacyclin release. These data further illustrate the need to look for new explanations, targets and pathways to define the COX/NSAID/cardiovascular risk axis. Gene expression profiles in tissues from apoE−/−/COX-2−/− mice showed increased lymphocyte pathways that were validated by showing increased T-lymphocytes in plaques and elevated plasma Th1-type cytokines. In addition, we identified a novel target gene, rgl1, whose expression was strongly reduced by COX-2 deletion across all examined tissues. This study is the first to demonstrate that COX-2 protects vessels against atherosclerotic lesions independently of local vascular prostacyclin and uses systems biology approaches to identify new mechanisms relevant to development of next generation NSAIDs.

THU0090 Cardiovascular Morbidity in Patients with Ankylosing Spondylitis: A Population-Based Cohort Study

BackgroundIt is well recognized that rheumatoid arthritis is an independent risk factor for cardiovascular (CV) disease. For ankylosing spondylitis (AS), the literature on this risk is relatively scarce, and shows...

552 Serrated Epithelial Change is Associated With a Longer Time to Dysplasia in Patients With Chronic Ulcerative Colitis

Background: The chronic use of non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin, is associated with a reduction in risk for colorectal and other cancers. However, when used chronically, these drugs carry a significant side effect to induce GI bleeding. Our laboratory has developed a class of NSAIDs that are complexed with phosphatidylcholine (PC-NSAIDs) which have been shown in preclinical and clinical trials to reduce NSAID GI toxicity. To date these drugs have been shown to possess equal or better efficacy compared to traditional NSAIDs in regard to anti-inflammatory, analgesic and anti-pyretic activities. To evaluate the chemopreventive activity of PC-NSAIDs, an animal model of carcinogeninduced colonic aberrant crypts was tested. Methods: Rats were treated at two weekly intervals with azoxymethane (AOM, 15mg/kg), followed two weeks later by daily oral dosing with control or test drugs for 4weeks (indomethacin, 2mg/kg; indomethacin-PC, 2mgNSAID/ kg; ibuprofen, 20mg/kg; ibuprofen-PC, 20mg NSAID/kg; or aspirin-PC, 20mg NSAID/kg). Assessments were made of GI toxicity/bleeding by measurement of the hematocrit and of hemoglobin in the feces, and of chemopreventive efficacy by the number of aberrant crypts in the distal colon. Results: At the doses used, no GI toxicity was detected from any of the test agents. The number of colonic aberrant crypts were significantly reduced by treatment with indomethacin-PC, but not by indomethacin (AOM control=40±11; indomethacin= 46±9; indomethacin-PC=10±2). In a separate study colonic aberrant crypts were significantly reduced by treatment with ibuprofen-PC and aspirin-PC, but not by ibuprofen (AOM control=133±18; ibuprofen=189±32; ibuprofen-PC=76±8; aspirin-PC=86±24). Conclusions: At equivalent doses, a novel class of PC-NSAIDs exhibit enhanced chemopreventive activity over traditional NSAIDs in a rodent model of colon carcinogenesis. (Supported by NIH grants R41CA171408 and R03CA171613).

551 Phosphatidylcholine Association Enhances the Chemopreventive Activity of Non-Steroidal Anti-Inflammatory Drugs

Background: The chronic use of non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin, is associated with a reduction in risk for colorectal and other cancers. However, when used chronically, these drugs carry a significant side effect to induce GI bleeding. Our laboratory has developed a class of NSAIDs that are complexed with phosphatidylcholine (PC-NSAIDs) which have been shown in preclinical and clinical trials to reduce NSAID GI toxicity. To date these drugs have been shown to possess equal or better efficacy compared to traditional NSAIDs in regard to anti-inflammatory, analgesic and anti-pyretic activities. To evaluate the chemopreventive activity of PC-NSAIDs, an animal model of carcinogeninduced colonic aberrant crypts was tested. Methods: Rats were treated at two weekly intervals with azoxymethane (AOM, 15mg/kg), followed two weeks later by daily oral dosing with control or test drugs for 4weeks (indomethacin, 2mg/kg; indomethacin-PC, 2mgNSAID/ kg; ibuprofen, 20mg/kg; ibuprofen-PC, 20mg NSAID/kg; or aspirin-PC, 20mg NSAID/kg). Assessments were made of GI toxicity/bleeding by measurement of the hematocrit and of hemoglobin in the feces, and of chemopreventive efficacy by the number of aberrant crypts in the distal colon. Results: At the doses used, no GI toxicity was detected from any of the test agents. The number of colonic aberrant crypts were significantly reduced by treatment with indomethacin-PC, but not by indomethacin (AOM control=40±11; indomethacin= 46±9; indomethacin-PC=10±2). In a separate study colonic aberrant crypts were significantly reduced by treatment with ibuprofen-PC and aspirin-PC, but not by ibuprofen (AOM control=133±18; ibuprofen=189±32; ibuprofen-PC=76±8; aspirin-PC=86±24). Conclusions: At equivalent doses, a novel class of PC-NSAIDs exhibit enhanced chemopreventive activity over traditional NSAIDs in a rodent model of colon carcinogenesis. (Supported by NIH grants R41CA171408 and R03CA171613).

Prevalence of prescribing pattern of more than one NSAID in Pakistan

Nonsteroidal anti-inflammatory drugs (NSAIDs) represent diverse group of drug with analgesic property and most frequently prescribed drug globally.This is first choice of drug with well demonstrated efficiency for the pain management primarily musculoskeletal disorder and osteoarthritis to treat mild to moderate pain.Although its serious toxicity related to GIT limits its expediency.”Big evil” have tendency to just cure pain relieving symptoms not disease.In this study we aimed to determine the prescribing practice of multiple NSAIDs in Pakistan by healthcare practitioner and their attitude towards patient life safety and what consequences are responsible for irrational practice of these most common OTC drug. For the purpose of this evaluation discriptive studies was conducted based on prescription reading and case histories of more than 200 patients to rule out prescribing habit of physicians. Prescription collected were mostly from emergency (80%) and general physicians (20%). Nearly everyone patient came with intense pain related with muscular and arthritis pain. About 69% patients were being prescribed by double NSAIDs in which acetaminophen ratio was mostly high with Diclofenac sodium (ratio of 60:35). Single practice of NSAIDs has reported just 25% but more than prescription containing multiple NSAIDs 6%. Traditional NSAIDs prescribed more frequently compared to selective NSAIDs by physician which makes patients susceptible to GIT associated toxicity. For the prophylaxis of NSAIDs associated GIT bleeding only 15% patients were coprescribe by H2 receptor blocker primarily ranitidine (15%) and PPis (7%) and other (2%). After careful consideration about prescribing habit of NSAIDs by physician we conclude that the irrational practices prevalence have been rising dangerously which needs careful consideration by health authorities.

Clinical trial data in support of changing guidelines in osteoarthritis treatment.

Goals for the management of osteoarthritis (OA) emphasize pain relief, reduction of inflammation, and improvement in functioning. Among pharmacological pain management interventions, nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently recommended as the most effective treatment option for OA. However, the use of traditional oral NSAIDs is associated with risk of serious adverse events involving the gastrointestinal, cardiovascular, and renal systems. Topical NSAIDs are an alternative with well-established tolerability and efficacy in the treatment of OA of the knee or hand. While the management of OA pain is evolving toward the more widespread use of topical NSAIDs, some OA management guidelines have yet to incorporate these agents in their recommendations. This review examines the efficacy and tolerability of topical NSAIDs, their current placement in OA management guidelines, and their potential role in enabling pain specialists to provide individualized care for their patients with OA.

Nonsteroidal Anti-Inflammatory Drugs and the Heart

Aspirin has been on the market for 115 years. Beginning with the marketing of indomethacin for the treatment of rheumatoid arthritis in 1963, at least 20 other nonsteroidal anti-inflammatory drugs (NSAIDs) with aspirin-like actions have been developed over the past 50 years,1 culminating with the introduction of a new class of selective inhibitors of cyclooxygenase (COX)-2, the coxibs, approximately 15 years ago.2 The NSAIDs represent the single most crowded family of drugs sharing the same therapeutic activities and mechanism of action, perhaps reflecting the unmet therapeutic need in the area of pain management and the large interindividual variability in response to these agents. NSAIDs provide symptomatic relief of pain and inflammation associated with a variety of human disorders, including the rheumatic diseases. Their shared therapeutic actions (ie, analgesic, anti-inflammatory, and antipyretic) are usually accompanied by mechanism-based adverse effects that can, at least in part, be attenuated as a function of individual pharmacokinetic or pharmacodynamic properties.1 Nuances in the tolerability of different NSAIDs had been described in the precoxib era on the basis of clinical trials of a few hundred patients treated for up to a few months with soft end points. More recently, however, important differences in safety have been demonstrated in head-to-head randomized comparisons of individual coxibs and 1 or more traditional NSAIDs that involved tens of thousands of patients treated for up to a few years with hard end points. Even more significantly, the interpretation of the effects of NSAIDs has been greatly enhanced by the availability, for the first time, of large, placebo-controlled trials that aimed to assess the potential for chemoprevention of colorectal cancer by rofecoxib or celecoxib. As a result of these developments, the whole field of NSAIDs has been illuminated during the past 15 years. Although epidemiological studies had previously associated …

Design, synthesis and structure–activity relationship studies of novel and diverse cyclooxygenase-2 inhibitors as anti-inflammatory drugs

Because of the pivotal role of cyclooxygenase (COX) in the inflammatory processes, non-steroidal anti-inflammatory drugs (NSAIDs) that suppress COX activities have been used clinically for the treatment of inflammatory diseases/syndromes; however, traditional NSAIDs exhibit serious side-effects such as gastrointestinal damage and hyper sensitivity owing to their COX-1 inhibition. Also, COX-2 inhibition-derived suppressive or preventive effects against initiation/proliferation/invasion/motility/recurrence/metastasis of various cancers/tumours such as colon, gastric, skin, lung, liver, pancreas, breast, prostate, cervical and ovarian cancers are significant. In this study, design, synthesis and structure–activity relationship (SAR) of various novel {2-[(2-, 3- and/or 4-substituted)-benzoyl, (bicyclic heterocycloalkanophenyl)carbonyl or cycloalkanecarbonyl]-(5- or 6-substituted)-1H-indol-3-yl}acetic acid analogues were investigated to seek and identify various chemotypes of potent and selective COX-2 inhibitors for the treatment of inflammatory diseases, resulting in the discovery of orally potent agents in the peripheral-inflammation model rats. The SARs and physicochemical properties for the analogues are described as significant findings. For graphical abstract: see Supplementary Material. (www.informahealthcare.com/enz)

The Role of PGE2 and its Corresponding Receptors (Ep1-4) in Oesophageal Carcinogenesis: Novel Therapeutics for Chemoprevention and/or Intervention

The incidence of oesophageal adenocarcinoma (OAC) is increasing. At present, OAC is the 7th leading cause of cancer deaths worldwide. The use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) reduce the progression from Barrett’s oesophagus (BO) to OAC. These cyclooxygenase (COX) targeted agents have demonstrated considerable promise, although long-term use has been associated with both gastrointestinal (GI) damage and increased cardiovascular risk. COX-2 overexpression is seen in BO and OAC patients and is a promising target for chemopreventive and/or therapeutic approaches. However, the unfavourable safety profile associated with long-term COX-2 targeting emphasizes the need to both understand and target specific downstream effector mechanisms. The role of pro-inflammatory prostaglandin E2 (PGE2) and its corresponding EP receptors have gained considerable attention in recent years, where they have been associated with tumourogenesis in a number of inflammatory-driven cancers, including OAC. This review will discuss the role of COX-derived PGE2 signalling in OAC development and progression, with specific emphasis on EP receptor expression and function. We will compare and contrast the potential of traditional NSAIDs, selective COX-2 inhibitors and EP antagonists as chemopreventive and/or therapeutic agents. Finally, we will discuss the promise of novel small molecule selective EP antagonists, which have recently been developed and are currently under clinical investigation.

NSAIDs for Musculoskeletal Pain Management: Current Perspectives and Novel Strategies to Improve Safety

Musculoskeletal disorders are a growing burden on the health care system in the United States. Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to assist in the management of mild-to moderate musculoskeletal pain. After the withdrawal of rofecoxib because of cardiovascular toxicity, the safety of these agents became a topic of controversy and confusion. Recent evidence is facilitating a better understanding of the risks and mechanisms by which NSAIDs cause injury. In an effort to raise awareness, this review addresses the current challenges, recent progress, and novel strategies for improving tolerability. With new data to help guide decision making and the anticipated increase in pharmacological options for managing musculoskeletal pain, the role of the managed care professional is particularly important in this evolving field. To review recommendations for the appropriate use of NSAIDs, incorporate risk/benefit analysis into decision making, and evaluate the efficacy and safety of recently approved and emerging NSAID formulations. Musculoskeletal-related conditions are a major public health burden. NSAIDs are among the most commonly used medications for musculoskeletal conditions. Since the introduction of selective cyclooxygenease-2 (COX-2) inhibitors (or coxibs), there has been ongoing discussion and debate about the safety of all NSAIDs. Current available evidence suggests both traditional NSAIDs and coxibs increase the risk of gastrointestinal and cardiovascular toxicity; however, with proper risk assessment, these dangers can be limited. Moreover, new and emerging NSAID formulations and delivery systems aim to enhance the effectiveness and reduce the toxicity associated with these anti-inflammatory agents.

Treatment of Low Back Pain: The Potential Clinical and Public Health Benefits of Topical Herbal Remedies

Treatment of Low Back Pain: The Potential Clinical and Public Health Benefits of Topical Herbal Remedies

Platelet-Rich Plasma as an Effective Treatment for Proximal Hamstring Injuries

A platelet-rich plasma (PRP) injection at the muscle origin is an effective treatment for proximal hamstring injuries by effectively reducing pain and increasing functional outcomes scores in both primary and recalcitrant injuries. Proximal hamstring injuries can be disabling, and several traditional conservative treatments (TCT), including physiotherapy and non-steroidal anti-inflammatory drugs, have been inconsistently successful. Corticosteroid injections have demonstrated success, but can exhibit adverse effects on local tissue. Open repair has shown good to excellent results, but carries inherent surgical risk. Platelet-rich plasma (PRP) has emerged as a safe, effective treatment for several orthopaedic pathologies. We propose a PRP injection at the muscle origin as a novel treatment for proximal hamstring injuries. An Institutional Review Board approved retrospective review yielded fifteen patients with seventeen proximal hamstring injuries. Twelve injuries failed TCT initially and were ultimately treated with a PRP injection at the hamstrings origin. Five patients were successfully treated with TCT alone. Analysis included pre- and post-treatment visual analog scores (VAS), Nirschl Phase Rating Scale (NPRS), and return to sport. There was no significant difference between the groups’ pre-treatment VAS (p=0.17) and NPRS (p=0.06) nor their post-treatment VAS (p=0.40) and NPRS (p=0.21). Both the TCT (p=0.01, p=0.01) and the PRP (p=<0.01, p=<0.01) groups demonstrated significant reduction in VAS and NPRS. All athletes returned to desired activity level without major complications. Treatment for proximal hamstring injuries can be challenging, especially cases refractory to TCT. In these instances, surgical repair has been previously advocated. We feel that in both refractory and primary cases, PRP is a safe, effective treatment and a viable alternative to operative intervention. Both our groups had significant reductions in VAS and NPRS, and all our athletes returned to sport without complications.