Nonsteriodal Anti-inflammatory Drugs Research Articles

Supramolecular nanofiber of indomethacin derivative confers highly cyclooxygenase-2 (COX-2) selectivity and boosts anti-inflammatory efficacy

Herein, we report a facile method for converting carboxylate-containing indomethacin (Idm) into a cyclooxygenase-2 (COX-2) selective inhibitor via the amidation of an unnatural peptide sequence (Nal-Nal-Asp). The resulting indomethacin amides (i.e., Idm-Nal-Nal-Asp) have high selectivity for COX-2, and can self-assemble into a one-component supramolecular hydrogel that acts as a ‘self-delivery’ system for boosting anti-inflammatory efficacy. Self-assembled Idm-Nal-Nal-Asp hydrogel robustly inhibits COX-2 expression in lipopolysaccharide (LPS)-activated Raw 264.7 macrophages while also exhibits superior anti-inflammatory and antioxidant activities via reactive oxygen species (ROS)-related NF-κB and Nrf2/HO-1 pathways. Moreover, a rabbit model of endotoxin-induced uveitis (EIU) reveals that the Idm-Nal-Nal-Asp hydrogel outperforms clinically used 0.1 wt% diclofenac sodium eye drops in terms of in vivo anti-inflammatory efficacy via topical instillation route. As a rational approach to designing and applying COX-2 selective inhibitors, this work presents a simple method for converting non-selective nonsteriodal anti-inflammatory drugs (NSAIDs) into highly selective COX-2 inhibitors that can self-assemble into supramolecular hydrogel for anti-inflammation applications.

Prospective observational study on clinical and epidemiological profile of adult patients presenting to the emergency department with suspected upper gastrointestinal bleed

Background and objectiveBleeding from the upper gastrointestinal (GI) tract is one of the common medical emergencies. In this study, we assessed patients’ socio-demographic and clinical characteristics and the association of clinical characteristics with treatment outcomes among patients with suspected upper gastrointestinal bleed (UGIB) presenting to the emergency department (ED). At present, there is a scarcity of data on UGIB in Northern part of India.Material and methodThe study was a single-center, prospective observational study conducted at an urban tertiary care center. Consecutive patients with suspected UGIB were enrolled in the study from August 2020 to February 2022. A detailed history was obtained, including demographic data such as age and sex, presenting complaints, history of presenting illness, history related to co-morbidities, addiction, and drug history. Pre-endoscopic Rockall and Glasgow-Blatchford Score were calculated for each patient. The patients were subsequently followed up till discharge from the hospital. The final outcomes with regard to mortality, need for blood transfusion, length of emergency department stay, and discharge were noted.Result141 patients were included in the study. The mean age of the patients with suspected UGIB was 48 ± 14 years. 115 (81.6%) patients were male. The most common co-morbidity was chronic liver disease (40;28.4%). The most frequent presenting complaint in this study was hematemesis (96; 68.1%), followed by melena (76;53.9%). The mean (Standard Deviation, SD) of the Rockall Score was 2.46 ± 1.75. The mean (SD) of the Glasgow Blatchford Score was 12.46 ± 3.15 in patients with UGIB.ConclusionIn our study, hematemesis was the most prevalent symptom of suspected UGIB, followed by melena. Portal hypertension was the most common cause of UGIB. Most frequent comorbidities in patients suspected of UGIB were alcohol intake, Nonsteriodal Antiinflammatory Drugs (NSAIDs) abuse, and co-morbidities such as underlying chronic liver disease, hypertension, and diabetes. Early endoscopy can be of great utility to reduce morbidity and mortality.

Fully Automated Electric-Field-Driven Liquid Phase Microextraction System with Renewable Organic Membrane As a Front End to High Performance Liquid Chromatography.

This article reports for the first time a programmable-flow-based mesofluidic platform that accommodates electric-field-driven liquid phase microextraction (μ-EME) in a fully automated mode. The miniaturized system is composed of a computer-controlled microsyringe pump and a multiposition rotary valve for handling aqueous and organic solutions at a low microliter volume and acts as a front-end to online liquid chromatographic separation. The organic membrane is automatically renewed and disposed of in every analytical cycle, thus minimizing analyte carry-over effects while avoiding analyst intervention. The proof-of-concept applicability of the automated mesofluidic device is demonstrated by the liquid chromatographic determination of nonsteriodal anti-inflammatory drugs in μ-EME processed complex samples (such as urine and influent wastewater) using online heart-cut approaches. Using 5 μL of 1-octanol, 7.5 μL of untreated sample and 7.5 μL of acceptor solution (25 mM NaOH), and 250 V for only 10 min in a stopped-flow mode, the extraction recoveries for the μ-EME of ibuprofen, ketoprofen, naproxen, and diclofenac exceed 40% in real samples. The flow-through system features moderately selective extraction regardless of the sample matrix constituents with repeatability values better than 13%.

Pharmacokinetic studies of naproxen amides of some amino acid esters with promising colorectal cancer chemopreventive activity

Naproxen (nap) is belonging to Non-steriodal anti-inflammatory drugs (NSAIDs) group of drugs that characterized by their free carboxylic group. The therapeutic activity of nap is usually accompanied by GI untoward side effects. Recently synthesized naproxen amides of some amino acid esters prodrugs to mask the free carboxylic group were reported. Those prodrugs showed a promising colorectal cancer chemopreventive activity. The current study aims to investigate the fate and hydrolysis of the prodrugs kinetically in different pH conditions, simulated gastric and intestinal fluids with pHs of 1.2, 5.5 and 7.4 in vitro at 37 °C. The effect of enzymes on the hydrolysis of prodrugs was also studied through incubation of these prodrugs at 37 °C in human plasma and rat liver homogenates. The pharmacokinetic parameters of selected prodrugs and the liberated nap were studied after oral and intraperitoneal administration in male wistar rats. The results showed the hydrolysis of naproxen amides of amino acid esters to nap through two steps first by degradation of the ester moiety to form the amide of nap with amino acid and the second was through the degradation of the amide link to liberate nap. The two reactions were followed and studied kinetically where K1 and K2 (rate constants of degradation) is reported. The hydrolysis of prodrugs was faster in liver homogenates than in plasma. The relative bioavailability of the liberated nap in vivo was higher in case of prodrug containing ethyl glycinate moiety than that occupied l-valine ethyl ester moiety. Each of nap. prodrugs containing ethyl glycinate and l-valine ethyl ester moieties appears promising in liberating nap, decreasing direct GI side effect and consequently their colorectal cancer chemopreventive activity.

Drug Allergy Clinical Characteristics in Pediatrics

Background: A drug allergy causes a morbidity and a mortality due to its various range of clinical manifestation. Unfortunately, a study focusing in pediatric drug allergy is insufficient, especially in Bandung. Thus, this study is conducted to determine the clinical characteristic of pediatric drug allergy in Dr. Hasan Sadikin General Hospital Bandung. Methods: This study was a retrospective descriptive study using medical records of pediatric drug allergy patients between 2010–2015 in Dr. Hasan Sadikin General Hospital Bandung taken with total sampling method. The variables were patient age, gender, causative drug, and clinical manifestation. Clinical manifestation was then divided into exanthem, urticaria, erythema multiforme, Steven-Johnson’s syndrome/toxic epidemiolytic necrosis (SJS/TEN), and fixed drug eruption (FDE). Results: Out of 101 patients, only 71 were included in the study due to incomplete medical records of the rest. There were 34 (47.89%) males and 37 (52.11%) females. Patients’ age ranged from 1–18 years old with the mean of 7.4 years old. The most common clinical manifestation was SJS/TEN with 25 (35.21%) patients, followed by exanthem with 22 (30.98%) patients. The most common suspected causative drug was non-steriodal anti inflammatory drugs (NSAID) (24%), followed with penicillin (21%). Conclusions: Most common manifestation of pediatric drug allergy in female is SJS/TEN, meanwhile in male is exanthema. Steven-Johnson’s syndrome/toxic epidemiolytic necrosis mostly occurs at the age group of 12–18 years old, and exanthema at the age group of 0–3 years old. This condition is mostly caused by NSAID and penicillin . DOI: 10.15850/amj.v4n2.1097

Design and Synthesis of New Non-Steroidal Anti-inflammatory Agents with Expected Selectivity toward Cyclooxygenase-2 Inhibition

This study includes design and synthesis of new non-steroidal anti-inflammatory agents (NSAIDs) with expected cyclooxygenase-2 (COX-2) selective inhibition to achieve better activity and low gastric side effects. Two series of compounds have been designed and synthesized as potential NSAIDs,these are: Salicylamide derivatives (compounds 3,4,5 ) and Diflunisal derivatives (compounds 10&11). In vivo acute anti-inflammatory effect of one of the synthesized agents (compound 3) was evaluated in the rat using egg-white induced paw edema model of inflammation. Preliminary pharmacological study revealed that compound 3 exhibited less anti-inflammatory effect compared to that of aspirin after 120 and 210 minutes, which encourage the continuation of the search to demonstrate or identify the preliminary pharmacological activity for the synthesized compounds and to identify their selectivity toward COX-2 isoenzymes.
 Keywords:nonsteriodal anti-inflammatory drugs(NSAID),aspirin derivatives ,diflunisal, Cyclooxygenase -1(cox-1),cyclooxygenase-2(cox-2)

Docking Studies, Synthesis and Biological Evaluation of β-aryl-β-hydroxy Propanoic Acids for Anti-inflammatory Activity.

Nonsteriodal anti-inflammatory drugs (NSAIDs) are numerous and widely used for more than 60 years, but there is still a strong need for developing novel selective NSAIDs. The need is justified by the fact that nonselective NSAIDs can produce serious gastric side effects and that some of the selective NSAID are withdrawn due to their cardiotoxic side effects. Eight β-hydroxy-β-arylpropanoic acids, which belong to the arylpropanoic acid class of compounds, structurally similar to some nonsteroidal anti-inflammatory drugs (NSAIDs), were docked into 3D catalytic site of both cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). Seven out of those eight acids were synthesized using already published modification of Reformatsky reaction additionally optimized by increasing temperature. Synthesized compounds were tested in vivo in order to elucidate anti-inflammatory activity, gastric tolerability and impact on liver function of rats. Results of docking studies have indicated that all compounds have potential to selectively inhibit COX-2 isoform, but that the compounds containing polar substituents on phenyl ring are better inhibitors. Results of carrageenan-induced rat paw oedema test have shown that all compounds exhibit dose dependence and good gastric tolerability and none of the tested compounds have shown negative effect on liver function compared to ibuprofen. The compound containing polar nitro group in para position has shown the best docking results, anti-inflammatory activity, low hepatotoxicity and good gastric tolerability.

Indomethacin induces increase in gastric epithelial tight junction permeability via redistribution of occludin and activation of p38 MAPK in MKN-28 Cells

Tight Junctions (TJ) create a paracellular barrier that is compromised when nonsteriodal anti-inflammatory drugs (NSAIDs) injure the gastric epithelium, leading to increased permeability. However, the mechanism of NSAID-induced gastric injury is unclear. Here, we examined the effect of indomethacin on barrier function and TJ in gastric MKN-28 cells. In concentration response studies, 500 µm indomethacin induced a significant decrease in transepithelial resistance (TER; 380 vs. 220 Ω·cm2 for control and indomethacin-treated cells respectively, p < 0.05), and increased dextran permeability by 0.2 vs 1.2 g/l (p < 0.05). These changes in barrier function were completely ameliorated by the p38 MAPK inhibitor (SB-203580) but not by JNK inhibitor (SP-600125) or MEK/ERK inhibitor (PD-98059). SiRNA knock down of p38 MAPK prevented the loss of barrier function caused by indomethacin in MKN-28 cells. Western analyses of TJ proteins revealed that expression of occludin was reduced by indomethacin, whereas there was no change in other TJ proteins. The loss of occludin expression induced by indomethacin was prevented by inhibition of p38 MAPK but not JNK or ERK and also by siRNA of p38 MAPK. Immunofluorescence revealed disruption of occludin localization at the site of the tight junction in indomethacin-treated cells, and this was attenuated by inhibition of p38 MAPK. NSAID injury to murine gastric mucosa on Ussing chambers revealed that indomethacin caused a significant drop in TER and increased paracellular permeability. Pretreatment with the p38 MAPK inhibitor significantly attenuated the disruption of barrier function, but JNK and MEK/ERK inhibition had no effect. Western blot analysis on gastric mucosa reveled loss of TJ protein occludin by indomethacin, which was prevented by inhibition of p38 MAPK. This data suggests that indomethacin compromises the gastric epithelial barrier via p38 MAPK inducing occludin alterations in the TJs.

Pediatric Tonsillectomy and Ketorolac

The use of ketorolac in children undergoing tonsillectomy remains limited because of the concern about postoperative bleeding. A search was performed addressing the question: For patients undergoing a surgical tonsillectomy, does a weight-appropriate single dose of intravenous ketorolac affect the incidence of postoperative hemorrhage? Five systematic reviews met the inclusion criteria. A Cochrane Review included 15 studies with 1,101 pediatric subjects and focused on perioperative bleeding requiring intervention. Many of the systematic reviews appraised the same studies. Subgroup analysis often allowed assessment of the effects of ketorolac administration. There was no consensus on the increased risk of bleeding when nonsteriodal anti-inflammatory drugs such as ketorolac are given to pediatric patients undergoing tonsillectomy. The conclusions varied from ketorolac should not be used to it is safe to use with these patients. The perianesthesia team must carefully weigh the risks and benefits before deciding to use ketorolac with this subset of patients.

Review Article: Fabricated Microparticles: An Innovative Method to Minimize the Side Effects of NSAIDs in Arthritis.

Microparticles are polymeric bodies ranging 1-1000 µm that constitute a variety of forms such as microcapsules, microspheres, microcages, microshells, microrods, biosensors microparticles, radiolabeled microparticles, and so forth. This review focuses on general microparticles, mainly microcapsules and microspheres. Nonsteriodal anti-inflammatory drugs (NSAIDs) are one of the mostcommonly prescribed medications in the world. Most of the NSAIDs available have severe side effects. With increased awareness of NSAID-induced gastrointestinal (GI) side effects, safety has become a priority in treatment of arthritis and other inflammatory diseases with NSAIDs. A trend in NSAID development has been to improve therapeutic efficacy while reducing the severity of GI side effects by altering dosage through modified release to optimize drug delivery. One such approach is the use of fabricated microparticles such as microcapsules and microspheres as carriers of drugs. Microparticles provide delivery of macromolecules and micromolecules via different routes and effectively control the release profile of such drugs. Microcapsules and microspheres are compatible with most natural and synthetic polymers and can be used for several routes of administration, including parenteral, oral, nasal, intra-ocular, topical, and the like. Because of greater stability and multiple manufacturing techniques, microspheres and microcapsules are preferred as drug carriers over other colloidal drug delivery systems. Microparticles provide effective protection of the encapsulated agent against degradation by enzymatic activities, controlled and confined delivery of drugs from a few hours to months, and ingenious administration compared to alternative forms of controlled-release parenteral dosages, such as macro-sized implants. This comprehensive overview of fabricated microparticles describes microencapsulation technologies to produce microparticles for targeted therapy of arthritis and other inflammatory diseases which provide constant and prolonged therapeutic effects that reduce dosing frequency and thereby minimize potential adverse effects of NSAIDs such as GI irritation and insufficient patient compliance. The present review describes the latest developments in microparticulate drug delivery systems and the best alternatives for safe and effective microcapsular systems in a controlled manner for the delivery of NSAIDs.

Decision making in third molar surgery: a survey of Brazilian oral and maxillofacial surgeons

This study was designed to evaluate the variations in decision making among Brazilian oral and maxillofacial surgeons (OMFS) and trainees in relation to third molar surgery. A survey on 18 diverse clinical situations related to the assessment and treatment of the third molar surgeries was conducted during the 20th Brazilian National OMFS meeting. Participants were divided into three groups according to their level of training. Another variable studied was length of experience. Correlation between the question answers and the variables was analysed using the chi-square test and the f test. The mean age of participants was 32.68 years, and their mean length of experience was 5.24 years. There were no statistical differences between the level of training and number of years of experience and the responses to 15 of the 18 questions on clinical situations. However, differences were found in responses to prophylactic extraction of asymptomatic third molars, use of non-steriodal anti-inflammatory drugs (NSAIDs) during the preoperative surgical period and the use of additional imaging to plan extractions. The group with shorter time of experience (3.8 ± 3.94 years) tended to recommend extractions of asymptomatic third molars more frequently compared with the more experienced surgeons (P = 0.041). More experienced surgeons used NSAIDs in the preoperative surgical period, whereas the majority of the youngest surgeons (4.1 ± 5.96 years of experience) did not (P = 0.0042). The certificated trained and in practice group tended to treat deep lower third molar impactions based on the findings of a panoramic radiograph, without obtaining additional imaging [cone beam computed tomography (CBCT)] before treatment (P = 0.0132). Decision making regarding third molar treatment differs according to the level of training and is influenced by the number of years of experience. Therefore, further continuous education programmes in this area are warranted to make recommendations regarding third molars consistent with the current literature.

External Validation of a Referral Rule for Axial Spondyloarthritis in Primary Care Patients with Chronic Low Back Pain.

ObjectivesTo validate and optimize a referral rule to identify primary care patients with chronic low back pain (CLBP) suspected for axial spondyloarthritis (axSpA).DesignCross-sectional study with data from 19 Dutch primary care practices for development and 38 for validation.ParticipantsPrimary care patients aged 18-45 years with CLBP existing more than three months and onset of back pain started before the age of 45 years.Main OutcomeThe number of axSpA patients according to the ASAS criteria.MethodsThe referral rule (CaFaSpA referral rule) was developed using 364 CLBP patients from 19 primary care practices and contains four easy to use variables; inflammatory back pain, good response to nonsteriodal anti-inflammatory drugs, family history of spondyloarthritis and a back pain duration longer than five years. This referral rule is positive when at least two variables are present. Validation of the CaFaSpA rule was accomplished in 579 primary care CLBP patients from 38 practices from other areas. Performance of the referral rule was assessed by c-statistic and calibration plot. To fit the final referral rule the development and validation datasets were pooled leading to a total study population of 943 primary care participants.ResultsThe referral rule was validated in 579 patients (41% male, mean age 36 (sd7.0). The percentage of identified axSpA patients was 16% (n=95). External validation resulted in satisfactory calibration and reasonable discriminative ability (c-statistics 0.70 [95% CI, 0.64-0.75]). In the pooled dataset sensitivity and specificity of the referral rule were 75% and 58%.ConclusionsThe CaFaSpA referral rule for axSpA consists of four easy to use predictors for primary care physicians and has a good predictive value in this validation study. The referral rule has the potential to be a screening tool for primary care by identifying CLBP patients suspected for axSpA.

Nonsteroidal anti-inflammatory drugs: An unusual cause of multiple ileal perforations

Introduction: In this case report, we describe a rare case of pneumoperitoneum with peritonitis due to multiple ileal perforations with a history of high doses of diclofenac sodium usage. case report: A young adult male with recent history of high doses of Nonsteroidal anti-inflammatory drugs (NsAIDs) presented in emergency department with acute onset pain in right iliac fossa with high grade fever and tachycardia for 12 hours. Abdomen was tender in the right iliac fossa with guarding. X-ray of chest showed free gas under the diaphragm. Exploratory laparotomy was done and showed multiple ileal perforations. ressection and anastomosis of the affected segment was done, both ends brought as double barrel ileostomy which was reversed later on without any complication. conclusion: High doses of Nonsteriodal anti-inflammatory drugs can cause multiple ileal erosions and perforation and should be considered in the the differential diagnosis, if other possibilities are excluded.

Increased diverticular complications with nonsteriodal anti‐inflammatory drugs and other medications: a systematic review and meta‐analysis

Complications of colonic diverticula, perforation and bleeding are a source of morbidity and mortality. A variety of drugs have been implicated in these complications. We present a systemic review and meta-analysis of the literature to assess the importance of this relationship. A systematic review of articles in PubMed, Cochrane Reviews, Embase and Google Scholar was undertaken in February 2013. An initial literature search yielded 2916 results that were assessed for study design and topicality. Twenty-three articles were included in the review. A qualitative data synthesis was conducted using forest plots of studies comparing single medication with complications. Individual studies demonstrated the odds of perforation and abscess formation with nonsteridal anti-inflammatory drugs (NSAIDs) (1.46-10.30), aspirin (0.66-2.40), steroids (2.17-31.90) and opioids (1.80-4.51) and the odds of bleeding with NSAIDs (2.01-12.60), paracetamol (0-3.75), aspirin (1.14-3.70) and steroids (0.57-5.40). Pooled data showed significantly increased odds of perforation and abscess formation with NSAIDs (OR = 2.49), steroids (OR = 9.08) and opioids (OR = 2.52). They also showed increased odds of diverticular bleeding from NSAIDs (OR = 2.69), aspirin (OR = 3.24) and calcium-channel blockers (OR = 2.50). Most studies did not describe the duration or dosage of medication used and did not systematically describe the severity of diverticular complications. Various common medications are implicated in complications of diverticular disease.

Drug Design and Analysis In Silico of Sapelenin G, an Acyclic Triterpenoid as Potential Anti-Inflammatory

Diverse non-steriodal anti-inflammatory drugs and COX-2 inhibitors are a class of drugs which selectively inhibit COX-2, provide relief from pain and inflammation. However, they lack anti-thrombotic activity and hence lead to cardiovascular and renal liabilities apart from gastrointestinal irritation. To ameliorate this situation, research can be foccuss on the products originating from natural products that could offer better relief from inflammation than the currently used commercial drugs. Aspirin blocks the cyclooxygenase enzyme (COX 1, 2) which is involved in the ring closure and the addition of O2 to arachidonic acid, converting it to prostaglandins (which induce inflammation, pain and fever). The present study is undertaken to analyse the docking efficacy of aspirin with the target molecule (2AW1), to assess the best ligand for inhibiting COX and to analyze the docking program by Arguslab. Substituting aspirin ligand by sapelenin G, the finding sug - gests that sapelenin G is a better ligand than aspirin. It satisfies Lipinski Rule of 5. The PASS (Prediction of Activity Spectra for Substances) prediction results show that Sapelenin G has an anti-inflammatory activity. Toxicity estimations of Sapelenin G using Toxtree on humans and based on the Cramer rules, Verhaar, Structural Alerts for Reactivity in Toxtree (START) biodegradability, eye irritation/corrosion and skin irritation/corrosion fell into class 3, 5, 1, 2 and 1, respectively. Application of the Benigni-Bossa method showed that this compound is negative for genotoxic carcinogenicity and negative for non-genotoxic carcinogenicity. The cytochrome P-450 mediated drug metabolism is negative for Sapelenin G only in SMARTCyp.Rank2.sites of metabolism, and it fell into unreactive group of compounds by Michael ad- dition. A skin sensitization evaluation reveals that the compound has no skin sensitization alert identified, moreover, Kroes Threshold of Toxicological Concern (TTC) decision tree reveals that the Substance would not be expected to be a safety concern.

Influence of Levamisole and Other Angiogenesis Inhibitors on Angiogenesis and Endothelial Cell Morphology in Vitro

Angiogenesis, the formation of new blood vessels from existing vessels is required for many physiological processes and for growth of solid tumors. Initiated by hypoxia, angiogenesis involves binding of angiogenic factors to endothelial cell (EC) receptors and activation of cellular signaling, differentiation, migration, proliferation, interconnection and canalization of ECs, remodeling of the extracellular matrix and stabilization of newly formed vessels. Experimentally, these processes can be studied by several in vitro and in vivo assays focusing on different steps in the process. In vitro, ECs form networks of capillary-like tubes when propagated for three days in coculture with fibroblasts. The tube formation is dependent on vascular endothelial growth factor (VEGF) and omission of VEGF from the culture medium results in the formation of clusters of undifferentiated ECs. Addition of angiogenesis inhibitors to the coculture system disrupts endothelial network formation and influences EC morphology in two distinct ways. Treatment with antibodies to VEGF, soluble VEGF receptor, the VEGF receptor tyrosine kinase inhibitor SU5614, protein tyrosine phosphatase inhibitor (PTPI) IV or levamisole results in the formation of EC clusters of variable size. This cluster morphology is a result of inhibited EC differentiation and levamisole can be inferred to influence and block VEGF signaling. Treatment with platelet factor 4, thrombospondin, rapamycin, suramin, TNP-470, salubrinal, PTPI I, PTPI II, clodronate, NSC87877 or non-steriodal anti-inflammatory drugs (NSAIDs) results in the formation of short cords of ECs, which suggests that these inhibitors have an influence on later steps in the angiogenic process, such as EC proliferation and migration. A humanized antibody to VEGF is one of a few angiogenesis inhibitors used clinically for treatment of cancer. Levamisole is approved for clinical treatment of cancer and is interesting with respect to anti-angiogenic activity in vivo since it inhibits ECs in vitro with a morphology resembling that obtained with antibodies to VEGF.

FOCAL THERAPY OF OSTEOARTHRITIS — NEW OPTIONS

Система комплексной поддержки и сопровождения научного журнала Elpub позволяет запустить двуязычный сайт журнала со встроенной системой электронной редакции в соответствии с лучшими издательскими практиками, а так же предусматривает техническую и методическую поддержку со стороны специалистов НЭИКОН.

HMG CoA reductase inhibitors, NSAIDs and risk of glioma

3-Hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors (statins) have shown inverse associations with cancer risks, but the results have been inconsistent. As there are no previous published data in brain tumors, we conducted a case-control study to investigate statin therapy and risk of glioma. We further evaluated the use of nonsteriodal anti-inflammatory drugs (NSAIDs) and risk of these tumors. We recruited newly diagnosed glioma cases and frequency matched controls at Columbia University and the University of California San Francisco. Standardized questions on statins and NSAIDs were used at both institutions. Intakes of these drugs were defined as >6 months of at least twice weekly use versus less than this amount or never use. From July 2007 to January 2010, we recruited a total of 517 cases and 400 controls. Simvastatin and lovastatin showed significant inverse associations with glioma (odds ratio [OR] = 0.49, 95% confidence interval [CI] 0.30, 0.81 and OR = 0.47, 95% CI 0.24, 0.93, respectively). For NSAIDs, aspirin use was also inversely related to glioma risk (OR = 0.68, 95% CI 0.49, 0.96). Both statins and NSAIDs showed significant inverse trends between the duration of drug use and glioma risk (trend tests p = 0.03 and p = 0.02, respectively), and drug intake for >120 months demonstrated the most significant associations for both types of medication. The inverse association between statin therapy and risk of glioma supports the roles of Ras/Rho GTPases or inflammatory cytokines in gliomagenesis, and a similar relationship between NSAIDs and glioma highlights the importance of cyclo-oxygenase 2 in glioma pathogenesis.

Desmoid tumour of the breast as a manifestation of Gardner's syndrome

INTRODUCTIONDesmoid tumours of the breast are rare. Although benign, they can mimic breast cancer on physical examination, mammography and breast ultrasound and can also be locally invasive. Even though they occur sporadically, they can also be seen as a part of Gardner's syndrome. We describe a case of desmoid tumour in a woman with Gardner's syndrome where the lesion was mammographically occult. PRESENTATION OF CASEA 63-year old woman presented with four months history of a painful left breast lump. She had a screening mammogram seven months ago which was normal. She is known to have Gardner's syndrome and had a total colectomy, she has also had multiple abdominal desmoids excised in the past. On examination there was a 4cm×5cm firm, mobile lump in the left breast. Her mammograms in the clinic were also normal. Ultrasound suggested a benign lesion of the breast and a core biopsy showed it to be a benign spindle cell lesion. She underwent wide local excision of the lump, the intraoperative mammograms of the excised specimen also failed to detect the lesion. Histopathology of the excised specimen confirmed the tumour to be a benign desmoid tumour. She has now been offered radiotherapy and nonsteriodal anti-inflammatory drugs (NSAIDs) to reduce her chances of a local recurrence. CONCLUSIONA high index of suspicion and a thorough triple examination protocol is necessary to detect rare lesions like a desmoid tumour which can masquerade as breast carcinoma.

Current and Future Therapeutic Targets of Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic systematic autoimmune disease which affects about 1% of the population world wide. This article aimed to identify current therapeutic targets for RA based on data from the literature and drug target related databases. Identified targets were further analysed using a powerful bioinformatics tool, PANTHER (Protein ANalysis THrough Evolutionary Relationships). Additionally, we explored future possible therapeutic targets for RA and discussed the possibility of discovering novel drugs with improved efficacy and reduced toxicity for RA treatment. Data on current clinical drugs for RA treatment were extracted from the US Food and Drugs Administration (FDA) website. Candidate targets of RA were extracted from three online databases: Drugbank, Therapeutic Target Database (TTD) and Potential Drug Target Database (PDTD). A total of 95 clinical protein targets for RA have been identified and were analysed using the PANTHER Classification System. According to the PANTHER analysis, most commonly involved pathways in current RA targeting includes inflammation mediated by chemokine and cytokine signalling pathways, angiogenesis, p53 pathway, de novo purine biosynthesis, T-cell activation, apoptosis signalling pathway and vascular endothelial growth factor (VEGF) receptor signalling pathway. Accordingly, current clinical agents for the treatment of RA mainly include corticosteroids, non-steriodal anti-inflammatory drugs (NSAIDs) and disease-modifying antirheumatic drugs (DMARDs). In addition, a number of investigational targets for RA have been identified and many novel drugs for RA therapy are under investigation. Current approaches to handle RA aim to ameliorate inflammation, to relieve pain, and most importantly to protect the cartilage, joints and bones from further damage by blocking proinflammatory molecules and inhibit the production of matrix-degrading factors. New drugs for RA with improved efficacy and safety should be developed.