Mecanismo de los AINES y antiinflamatorios derivados para el control del dolor y la inflamación. Uso de antiinflamatorios en odontología / Mechanism of NSAIDs and derived drugs for pain and inflammation control. Use of anti-inflammatories in odontology

Las urgencias odontológicas son, quizá, las razones principales de atención en el consultorio, muchas veces el significado de dolor se encuentra acompañado por inflamación; el uso de antiinflamatorios no esteroideos (AINES) es común en el ejercicio de la odontología por la excelente respuesta analgésica y antiinflamatoria que tiene, por lo que es importante conocer la fisiopatología de la inflamación y el dolor y cómo actúan los AINES, ya que algunos de estos fármacos tienen respuestas adversas y sitios de acción importantes. Los factores de riesgo por inflamación y dolor nos obligan a conocer la variedad de fármacos que no entran en la clasificación de AINES y que tenemos a disposición, hay más opciones para la elección ante la presencia de inflamación por un factor en particular, cada uno de éstos tienen indicaciones y contraindicaciones que conoceremos, lo cual nos ampliará el conocimiento para dar una prescripción ante la presencia de eventos inflamatorios. Se realizó un estudio detallado de artículos bibliográficos de cada tema, los fármacos más usados en odontología son los AINES, hay poco uso y conocimiento de antiinflamatorios que podemos usar en urgencias, el porcentaje de uso de los AINES derivados del ácido propiónico es alto por la excelente respuesta en pacientes y otras veces por el desconocimiento de más opciones (AU)

Dental emergencies are perhaps the main reasons for care in the office, many times the meaning of pain is accompanied by inflammation, the use of non-steroidal anti-inflammatory drugs is common in the practice of dentistry due to the excellent analgesic and anti-inflammatory response it has, important is knowing the pathophysiology of inflammation and pain, how NSAIDs act, some of these drugs have adverse responses and important sites of action, risk factors for inflammation and pain require us to know the variety of drugs that do not enter the classification of NSAIDs and we have at our disposal, there are more options for choosing in the presence of inflammation due to a particular factor, each of these have indications and contraindications that we will know, it expands our knowledge to give a prescription in the presence of inflammatory events. A detailed study of bibliographic articles on each topic was carried out, the drugs most used in dentistry are NSAIDs, there is little use and knowledge of anti-inflammatories that we can use in the emergency room, the percentage of use of NSAIDs derived from propionic acid is high, due to the excellent response in patients and others due to lack of knowledge of more options (AU)

Panax Notoginseng Saponin Attenuates Gastric Mucosal Epithelial Cell Injury Induced by Dual Antiplatelet Drugs through COX and PI3K/Akt/ VEGF-GSK-3β-RhoA Network Pathway / 中国结合医学杂志

OBJECTIVE@#To elucidate the underlying mechanism of Panax notoginseng saponin (PNS) on gastric epithelial cell injury and barrier dysfunction induced by dual antiplatelet (DA).@*METHODS@#Human gastric mucosal epithelial cell (GES-1) was cultured and divided into 4 groups: a control, a DA, a PNS+DA and a LY294002+PNS+DA group. GES-1 apoptosis was detected by flow cytometry, cell permeability were detected using Transwell, level of prostaglandins E2 (PGE2), 6-keto-prostaglandin F1α (6-keto-PGF1α) and vascular endothelial growth factor (VEGF) in supernatant were measured by enzyme linked immunosorbent assay (ELISA), expression of phosphatidylinositide 3-kinase (PI3K), phosphorylated-PI3K (p-PI3K), Akt, phosphorylated-Akt (p-Akt), cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), glycogen synthase kinase-3β (GSK-3β) and Ras homolog gene family member A (RhoA) were measured by Western-blot.@*RESULTS@#DA induced apoptosis and hyper-permeability in GES-1, reduced supernatant level of PGE2, 6-keto-PGF1α and VEGF (P<0.05). Addition of PNS reduced the apoptosis of GES-1 caused by DA, restored the concentration of PGE2, 6-keto-PGF1α and VEGF (P<0.05). In addition, PNS attenuated the alteration of COX-1 and COX-2 expression induced by DA, up-regulated p-PI3K/p-Akt, down-regulated RhoA and GSK-3β. LY294002 mitigated the effects of PNS on cell apoptosis, cell permeability, VEGF concentration, and expression of RhoA and GSK-3β significantly.@*CONCLUSIONS@#PNS attenuates the suppression on COX/PG pathway from DA, alleviates DA-induced GES-1 apoptosis and barrier dysfunction through PI3K/Akt/ VEGF-GSK-3β-RhoA network pathway.

Structural Assessment of Chemical Constituent of Sidaguri (Sida rhombifolia Linn) and Its Ability to Inhibit Cyclooxygenase

Objective: To elicit the structure of isolated compounds from roots of sidaguri (Sida rhombifolia Linn). Material and Methods: Several organic standard protocols were involved, including extraction, fractionation, and phytochemical testing. Further spectroscopy methods, FTIR and 1HNMR, were used to determine the predicted structure of molecules, while their ability to inhibit cyclooxygenase (COX 1 and 2) were tested using in vitro method. Results: Overall assessments showed that the structure of the sidaguri is a long chain aliphatic carboxylic acid and identified as Z-3, 6, 6 trimethylhept-2-en-1-ol (T12) and nonanoic (T13). Both isolates significantly inhibit COX-1 and COX-2 non-selectively (the COX-1/COX-2 ratio for T12 was 0.91 and 0.82; while COX-1/COX-2 ratio for T13 was 0.89 and 0.87 at concentrations of 0.05 and 0.025 µg/mL respectively). Conclusion: The active compounds of Sidaguri have antiinflammatory effect by inhibiting COX non-selectively.

Complementary Participation of Genetics and Epigenetics in Development of NSAID-exacerbated Respiratory Disease

Nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (NERD) has attracted a great deal of attention because of its association with severe asthma. However, it remains widely underdiagnosed in asthmatics as well as the general population. Upon pharmacological inhibition of cyclooxygenase 1 by NSAIDs, production of anti-inflammatory prostaglandin E2 and lipoxins ceases, while release of proinflammatory cysteinyl leukotrienes increases. To determine the underlying mechanisms, many studies have attempted to elucidate the genetic variants, such as single nucleotide polymorphisms, responsible for alterations of prostaglandins and leukotrienes, but the results of these genetic studies could not explain the whole genetic pathogenesis of NERD. Accordingly, the field of epigenetics has been introduced as an additional contributor to genomic alteration underlying the development of NERD. Recently, changes in CpG methylation, as one of the epigenetic components, have been identified in target tissues of NERD. This review discusses in silico analyses of both genetic and epigenetic components to gain a better understanding of their complementary roles in the development of NERD. Although the molecular mechanisms underlying NERD pathogenesis remain poorly understood, genetic and epigenetic variations play significant roles. Our results enhance the understanding of the genetic and epigenetic mechanisms involved in the development of NERD and suggest new approaches toward better diagnosis and management.

The role of vitamin C in the gene expression of oxidative stress markers in fibroblasts from burn patients

Abstract Purpose: To assess the action of vitamin C on the expression of 84 oxidative stress related-genes in cultured skin fibroblasts from burn patients. Methods: Skin samples were obtained from ten burn patients. Human primary fibroblasts were isolated and cultured to be distributed into 2 groups: TF (n = 10, fibroblasts treated with vitamin C) and UF (n = 10, untreated fibroblasts). Gene expression analysis using quantitative polymerase chain reaction array was performed for comparisons between groups. Results: The comparison revealed 10 upregulated genes as follows: arachidonate 12-lipoxygenase (ALOX12), 24-dehydrocholesterol reductase (DHCR24), dual oxidase 1 (DUOX1), glutathione peroxidase 2 (GPX2), glutathione peroxidase 5 (GPX5), microsomal glutathione S-transferase 3 (MGST3), peroxiredoxin 4 (PRDX4), phosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 1 (P-REX1), prostaglandin-endoperoxide synthase 1 (PTGS1), and ring finger protein 7 (RNF7). Conclusion: Cultured fibroblasts obtained from burn patients and treated with vitamin C resulted in 10 differentially expressed genes, all overexpressed, with DUOX1, GPX5, GPX2 and PTGS1 being of most interest.

New flavonoids and methylchromone isolated from the aerial parts of Baeckea frutescens and their inhibitory activities against cyclooxygenases-1 and -2 / 中国天然药物

In the present study, we carried out a phytochemical investigation of the ethanol extract of the aerial parts of Baeckea frutescens, which resulted in the isolation of two new flavonoid glycosides, myricetin 3-O-(5″-O-galloyl)-α-L-arabinofuranoside (1), 6-methylquercetin 7-O-β-D-glucopyranoside (2), one new methylchromone glycoside, 7-O-(4', 6'-digalloyl)-β-D-glucopyranosyl-5-hydroxy-2-methylchromone (3), together with three known compounds (4-6). The structures of these isolated compounds were established on the basis of 1D and 2D NMR techniques and chemical methods. The anti-inflammatory activities of the compounds 1-6 were evaluated for their inhibitory effects against cyclooxygenases-1 and -2 in vitro. Compounds 1-6 showed potent COX-1 and COX-2 inhibiting activities in vitro with IC values ranging from 1.95 to 5.54 μmol·L and ranging from 1.01 to 2.27 μmol·L, respectively.

New flavonoids and methylchromone isolated from the aerial parts of Baeckea frutescens and their inhibitory activities against cyclooxygenases-1 and -2 / 中国天然药物

In the present study, we carried out a phytochemical investigation of the ethanol extract of the aerial parts of Baeckea frutescens, which resulted in the isolation of two new flavonoid glycosides, myricetin 3-O-(5″-O-galloyl)-α-L-arabinofuranoside (1), 6-methylquercetin 7-O-β-D-glucopyranoside (2), one new methylchromone glycoside, 7-O-(4', 6'-digalloyl)-β-D-glucopyranosyl-5-hydroxy-2-methylchromone (3), together with three known compounds (4-6). The structures of these isolated compounds were established on the basis of 1D and 2D NMR techniques and chemical methods. The anti-inflammatory activities of the compounds 1-6 were evaluated for their inhibitory effects against cyclooxygenases-1 and -2 in vitro. Compounds 1-6 showed potent COX-1 and COX-2 inhibiting activities in vitro with IC values ranging from 1.95 to 5.54 μmol·L and ranging from 1.01 to 2.27 μmol·L, respectively.

Expression of COX-1 and COX-2 in the Platelet of Iron Deficiency Anemia Women at Childbearing Age and Its Clinical Significance / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To detect the expression level of cyclooxygenase-1（COX-1） and cyclooxygenase-2（COX-2） in the platelet of iron deficiency anemia（IDA）women at childbearing age and to explore its correlation with the different indexes of anemia and platelets.</p><p><b>METHODS</b>Forty female IDA patients at childbearing age and 35 healthy controls were enrolled in this study. The Flow cytometry was used to detect the expression of platelet COX-1 and COX-2，the platelet aggregation function as examined by turbidimetric method，and the levels of serum ferritin were analyzed by electrochemical luminescence method，the leval of serum iron was determined by ELISA，and the correlation of different indexes was analyzed.</p><p><b>RESULTS</b>Compared with healthy controls，the levels of platelet COX-1 and COX-2 were significantly lower in female IDA patients at Childbearing age（P<0.05），but platelet count（Plt），mean platelet volume（MPV） and platelet aggregation rate（PAgT）were not statistically different between the 2 groups（P > 0.05）. The expression level of platelet COX-1 positively correlated with those of Hb（r =0.623，P<0.01），serum iron（r =0.321，P<0.05） and HCT（r=0.305，P<0.05）. but the platelet COX-2 expression did not corelate with these indexs.</p><p><b>CONCLUSION</b>The expression of platelet COX-1 and COX-2 in female IDA patients at Childbearing age markedly decrease，and the expression level of platelet COX-1 closely relates with the severity of anemia，that possesses reference value for clinical diagnosis of female IDA patients at Childbearing age..</p>

Urticária crônica exacerbada por anti-inflamatórios não esteroidais e resposta aos antileucotrienos / Nonsteroidal anti-inflammatory drug-exacerbated chronic urticaria and response to antileukotrienes

Introdução: Pacientes com urticária crônica espontânea (UCE) frequentemente exacerbam com o uso de anti-inflamatórios não esteroidais (AINEs), que são medicamentos que inibem a ciclooxigenase 1 (COX-1) e levam a um desvio para produção de leucotrienos. Os antileucotrienos seriam uma opção terapêutica para aqueles que não respondam aos anti-histamínicos (AH1). Objetivo: O objetivo deste estudo foi avaliar a eficácia dos antileucotrienos nos pacientes com UCE exacerbada ou não pelos AINEs que não responderam apenas aos AH1. Método: Estudo retrospectivo com análise de prontuários eletrônicos de pacientes com UCE em seguimento ambulatorial. Todos os pacientes foram interrogados sobre a história de exacerbação ou não da UCE por AINEs. Além dos AH1, o montelucaste foi introduzido para todos os pacientes, em algum momento do acompanhamento. Foram avaliadas a resposta ao antileucotrieno e a presença da associação desta resposta à história de exacerbação com AINE. Resultados: Sessenta e dois pacientes participaram do estudo. A média de idade foi de 48,4 anos, sendo 82,3% do sexo feminino. Destes, 35 pacientes (56,5%) referiam piora da urticária com uso de AINEs, e, destes, 77,1% responderam ao antileucotrieno associado ao AH1. Dentre os 27 pacientes que não apresentavam UCE exacerbada por AINE, 48,1% obtiveram boa resposta ao uso de antileucotrieno associado ao AH1. Conclusão: A resposta ao antileucotrieno foi superior e estatisticamente significante (p = 0,031) no grupo de pacientes com UCE exacerbada por AINE. Portanto, a associação dos antileucotrienos aos AH1 seria uma opção eficaz e segura, sendo que essa associação se torna ainda mais relevante em pacientes que UC exacerbada por AINEs.

Introduction: Patients with chronic spontaneous urticaria (CSU) frequently show symptom exacerbation after the use of nonsteroidal anti-inflammatory drugs (NSAIDs) ­ drugs that inhibit cyclooxygenase-1 (COX-1) and affect leukotriene production. Antileukotrienes are considered a therapeutic option for patients who do not respond to antihistamines (AH1). Objective: The aim of this study was to assess the effectiveness of antileukotrienes in patients with CSU exacerbated or not by NSAIDs. Methods: In this retrospective study, the electronic charts of CSU outpatients were analyzed. All patients were inquired about history of CSU exacerbation or not by NSAIDs. In addition to AH1, treatment with montelukast was introduced to all patients at some point during follow-up. Response to antileukotriene treatment and association between treatment response and history of NSAID exacerbation were evaluated. Results: A total of 62 patients participated in the study. Mean age was 48.4 years, and 82.3% were female. Thirtyfive patients (56.5%) reported worsening of urticaria with the use of NSAIDs; 77.1% of these patients responded to antileukotriene combined with AH1. Of the 27 patients with no history of CSU exacerbation with NSAIDs, 48.1% showed a favorable response to antileukotrienes associated with AH1. Conclusion: Response to antileukotriene treatment was higher and statistically significant (p=0.031) in patients with NSAID-exacerbated CSU. Therefore, the association of antileukotrienes with AH1 could be a safe and effective treatment option, especially for patients with NSAIDexacerbated CSU.

Cyclooxygenase biology in renal function - literature review / Biología de la ciclooxigenasa en la función renal - Revisión de la literatura

Abstract The cyclooxygenase (COX) exists in two main isoforms, COX-1 and COX-2, which are present in the renal system to ensure its homeostasis. However, in different clinical situations, these enzymes can play a physiologic role in maintaining the integrity of this organ, and also be associated with the worsening of tissue injuries/damage. In this sense, an explanation of the true biological function of the isoforms of COX enables a better understanding of the physiology and pathology of the kidney, as well as a better understanding of the consequences of its inhibition by the use of drugs. This review aimed to study the biological role of the COX enzyme in the renal system in different clinical situations.

Resumen La ciclooxigenasa existe en dos isoformas principales: COX-1 y COX-2, estas se encuentran presentes en el sistema renal como parte de su homeostasis. Sin embargo, en algunas situaciones clínicas, las dos enzimas pueden desempeñar un papel en el mantenimiento de la integridad de este órgano, y en otras pueden estar asociadas a la evolución de daños y lesiones en los tejidos. En este sentido, el conocimiento de la verdadera función biológica de las isoformas de la COX permite una mejor comprensión de la fisiología y patología del riñón, así como una mejor comprensión de las consecuencias de su inhibición por el uso de medicamentos. El objetivo de esta revisión es estudiar la función biológica de la enzima COX en el sistema renal en diferentes situaciones clínicas.

Cyclooxygenase 1 [COX1] expression in type 2 diabetes mellitus: a preliminary study from north India

Background and purpose: The 6th edition of International Diabetes Federation, 2014 shows an estimate of 387 million people with Type 2 diabetes mellitus [T2DM] worldwide, expected to rise to 592 million by 2035. T2DM is a metabolic disorder, one of the reasons being oxidative stress due to impairment in antioxidant enzymes. It leads to several complications such as micro and macrovascular diseases. Cyclooxygenase1 [COX1] enzyme is the rate limiting factor for the arachidonic pathway leading to vascular wall contraction with angiotensin II occurring in heart diseases resulting from T2DM. COX1 determines 6-Keto Prostaglandin F1alpha [6-k-PGF1alpha] level, plays a major role in vasodilation and restricts macrophage platelet aggregation. The aim of the present study was to compare the COX1 expression and level of reactive oxygen species [ROS] in T2DM patients and controls at different time periods in human macrophages in order to find a biomarker or drug target

Subjects and methods: The study subjects consisted of 100 individuals, 50 each from T2DM patients and healthy sex/age matched controls. Cell proliferation by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide [MTT] assay and ROS measurement by 2',7'-dichlorofluorescein diacetate [DCFDA] staining were performed at different time periods [24, 48, 72 h]. COX1 mRNA expression was checked by relative quantification method after real-time polymerase chain reaction [RT-PCR]

Results: The MTT assay showed that cell viability was significantly higher at 48 h [P < 0.05]. ROS production was found to be lowest at 24 h by DCFDA staining. ROS levels were raised in T2DM patients as compared to controls. The quantitative RT-PCR analysis showed that the COX1 expression was higher in T2DM patients as compared to healthy controls although not significant [P > 0.05]

Conclusion: Although COX1 is known to be a "housekeeping" gene, our study showed that its expression can be correlated with the disease condition and be used as a marker. However, further studies are required in more number of samples from other ethnic populations to confirm the findings

Update on the Management of Aspirin-Exacerbated Respiratory Disease

Aspirin-exacerbated respiratory disease (AERD) is an adult-onset upper and lower airway disease consisting of eosinophilic nasal polyps, asthma, and respiratory reactions to cyclooxygenase 1 (COX-1) inhibitors. Management includes guideline-based treatment of asthma and sinus disease, avoidance of COX-1 inhibitors, and for some patients aspirin desensitization followed by high-dose aspirin therapy. Despite this, many patients have inadequately controlled symptoms and require multiple sinus surgeries. In this review, we discuss the current standard approaches to the management of AERD, and we introduce several therapeutics under development that may hold promise for the treatment of AERD.

Aspirin induces IL-4 production: augmented IL-4 production in aspirin-exacerbated respiratory disease

Aspirin hypersensitivity is a hallmark of aspirin-exacerbated respiratory disease (AERD), a clinical syndrome characterized by the severe inflammation of the respiratory tract after ingestion of cyclooxygenase-1 inhibitors. We investigated the capacity of aspirin to induce interleukin-4 (IL-4) production in inflammatory cells relevant to AERD pathogenesis and examined the associated biochemical and molecular pathways. We also compared IL-4 production in peripheral blood mononuclear cells (PBMCs) from patients with AERD vs aspirin-tolerant asthma (ATA) upon exposure to aspirin. Aspirin induced IL-4 expression and activated the IL-4 promoter in a report assay. The capacity of aspirin to induce IL-4 expression correlated with its activity to activate mitogen-activated protein kinases, to form DNA-protein complexes on P elements in the IL-4 promoter and to synthesize nuclear factor of activated T cells, critical transcription factors for IL-4 transcription. Of clinical importance, aspirin upregulated IL-4 production twice as much in PBMCs from patients with AERD compared with PBMCs from patients with ATA. Our results suggest that IL-4 is an inflammatory component mediating intolerance reactions to aspirin, and thus is crucial for AERD pathogenesis.

Evaluation of protein undernourishment on the condylar process of the Wistar rat mandible correlation with insulin receptor expression

The mandible condylar process cartilage (CP) of Wistar rats is a secondary cartilage and acts as a mandibular growth site. This phenomenon depends on adequate proteins intake and hormone actions, including insulin. Objectives The present study evaluated the morphological aspects and the expression of the insulin receptor (IR) in the cartilage of the condylar process (CP) of rats subjected to protein undernourishment. Material and Methods The nourished group received a 20% casein diet, while the undernourished group (U) received a 5% casein diet. The re-nourished groups, R and RR, were used to assess the effects of re-nutrition during puberty and adulthood, respectively. CPs were processed and stained with picro-sirius red, safranin-O and azocarmine. Scanning electron microscopy and immunohistochemistry were also performed. Results The area of the CP cartilage and the number of cells in the chondroblastic layer decreased in the U group, as did the thickness of the CP layer in the joint and hypertrophic layer. Renourishment during the pubertal stage, but not during the adult phase, restored these parameters. The cell number was restored when re-nutrition occurred in the pubertal stage, but not in the adult phase. The extracellular matrix also decreased in the U group, but was restored by re-nutrition during the pubertal stage and further increased in the adult phase. IR expression was observed in all CPs, being higher in the chondroblastic and hypertrophic cartilage layers. The lowest expression was found in the U and RR groups. Conclusions Protein malnutrition altered the cellularity, the area, and the fibrous cartilage complex, as well as the expression of the IRs. .

Pilot study of the use of Yin Qiao San in children with conventional antipyretic hypersensitivity

BACKGROUND: Children with a diagnosis of cross-reactive hypersensitivity to both paracetamol and nonsteroidal anti-inflammatory drugs are limited in their choice of antipyretics. OBJECTIVE: The aim of this pilot study is to evaluate the feasibility of using a Chinese proprietary medicine, Yin Qiao San (YQS), for fever relief. METHODS: A single centre, open label, prospective clinical trial exploring the tolerability and feasibility of using YQS for fever relief in children who are unable to use conventional antipyretic medications. Children between 1-18 years of age with hypersensitivity to multiple antipyretics were recruited. Eligible participants underwent an oral provocation test with YQS. Children who passed the oral provocation test were instructed to take a prescribed dose of YQS when the temperature was >38.0℃ and continued till the fever settled. Time taken for fever resolution and any adverse events were collected. RESULTS: A total of 21 children, mean age 10.7 years, had a diagnosis of paracetamol and ibuprofen hypersensitivity. All except one patient successfully tolerated an oral challenge of YQS. Of the 88 doses of YQS taken for fever over 38.0℃, 16 (18%) had documented temperature reduction 2 hours after ingestion and 30 (34%) had documented temperature reduction 4 hours after ingestion. There were 2 reports of urticaria after YQS use which were attributed to flare of recurrent spontaneous urticaria during the illness. None of the patients developed symptoms of circulatory compromise or respiratory distress. CONCLUSION: YQS is generally well tolerated in patients with paracetamol and ibuprofen hypersensitivity.

Possible roles of COX-1 in learning and memory impairment induced by traumatic brain injury in mice

People who suffer from traumatic brain injury (TBI) often experience cognitive deficits in spatial reference and working memory. The possible roles of cyclooxygenase-1 (COX-1) in learning and memory impairment in mice with TBI are far from well known. Adult mice subjected to TBI were treated with the COX-1 selective inhibitor SC560. Performance in the open field and on the beam walk was then used to assess motor and behavioral function 1, 3, 7, 14, and 21 days following injury. Acquisition of spatial learning and memory retention was assessed using the Morris water maze on day 15 post-TBI. The expressions of COX-1, prostaglandin E2 (PGE2), interleukin (IL)-6, brain-derived neurotrophic factor (BDNF), platelet-derived growth factor BB (PDGF-BB), synapsin-I, and synaptophysin were detected in TBI mice. Administration of SC560 improved performance of beam walk tasks as well as spatial learning and memory after TBI. SC560 also reduced expressions of inflammatory markers IL-6 and PGE2, and reversed the expressions of COX-1, BDNF, PDGF-BB, synapsin-I, and synaptophysin in TBI mice. The present findings demonstrated that COX-1 might play an important role in cognitive deficits after TBI and that selective COX-1 inhibition should be further investigated as a potential therapeutic approach for TBI.

Gastroprotective Effect of Cochinchina momordica Seed Extract in Nonsteroidal Anti-Inflammatory Drug-Induced Acute Gastric Damage in a Rat Model

BACKGROUND/AIMS: The major compounds of Cochinchina momordica seed extract (SK-MS10) include momordica saponins. We report that the gastroprotective effect of SK-MS10 in an ethanol-induced gastric damage rat model is mediated by suppressing proinflammatory cytokines and downregulating cytosolic phospholipase A2 (cPLA2), 5-lipoxygenase (5-LOX), and the activation of calcitonin gene-related peptide. In this study, we evaluated the gastroprotective effects of SK-MS10 in the nonsteroidal anti-inflammatory drug (NSAID)-induced gastric damage rat model. METHODS: The pretreatment effect of SK-MS10 was evaluated in the NSAID-induced gastric damage rat model using aspirin, indomethacin, and diclofenac in 7-week-old rats. Gastric damage was evaluated based on the gross ulcer index by gastroenterologists, and the damage area (%) was measured using the MetaMorph 7.0 video image analysis system. Myeloperoxidase (MPO) was measured by enzyme-linked immunosorbent assay, and Western blotting was used to analyze the levels of cyclooxygenase (COX)-1, COX-2, cPLA2, and 5-LOX. RESULTS: All NSAIDs induced gastric damage based on the gross ulcer index and damage area (p<0.05). Gastric damage was significantly attenuated by SK-MS10 pretreatment compared with NSAID treatment alone (p<0.05). The SK-MS10 pretreatment group exhibited lower MPO levels than the diclofenac group. The expression of cPLA2 and 5-LOX was decreased by SK-MS10 pretreatment in each of the three NSAID treatment groups. CONCLUSIONS: SK-MS10 exhibited a gastroprotective effect against NSAID-induced acute gastric damage in rats. However, its protective mechanism may be different across the three types of NSAID-induced gastric damage models in rats.

Garden rue inhibits the arachidonic acid pathway, scavenges free radicals, and elevates FRAP: role in inflammation / 中国天然药物

AIM@#In the present study, the anti-inflammatory and antioxidant activities of the methanol extract of Ruta graveolens leaves (RG-M) were evaluated using various in vivo and in vitro models.@*METHOD@#For anti-inflammatory activity, RG-M was administered by the oral route (p.o.) in a carrageenan-induced paw edema model, and by the intraperitoneal route (i.p.) in an exudative inflammation model. In vitro inhibition of cyclooxygenase and lipoxygenase enzymes was evaluated. In vitro antioxidant activity was also examined. Endogenous antioxidant status was further evaluated by ferric reducing ability of plasma model.@*RESULTS@#RG-M showed maximum inhibition of carrageenan-induced edema (100 mg·kg⁻¹ - 33.36%; 200 mg·kg⁻¹ - 45.32% and 400 mg·kg⁻¹ - 56.28%). In the exudative inflammation model, a significant reduction in leukocyte migration (200 mg·kg⁻¹ - 54.75% and 400 mg·kg⁻¹ - 77.97%) and protein exudation (200 mg·kg⁻¹ - 31.14% and 400 mg·kg⁻¹ - 49.91%) were observed. RG-M also exhibited inhibition of COX-1 (IC50 182.27 μg·mL⁻¹) and COX-2 (IC50 190.16 μg·mL⁻¹) as well as 5-LOX (IC50 215.71 μg·mL⁻¹). Antioxidant activity was significant with improved endogenous antioxidant status.@*CONCLUSION@#The results demonstrated the anti-inflammatory and antioxidant activity of RG-M with potent inhibitory effects on the arachidonic acid pathways.

Cordycepin-Enriched WIB801C from Cordyceps militaris Inhibits Collagen-Induced Ca2+i Mobilization via cAMP-Dependent Phosphorylation of Inositol 1, 4, 5-Trisphosphate Receptor in Human Platelets

In this study, we prepared cordycepin-enriched (CE)-WIB801C, a n-butanol extract of Cordyceps militaris-hypha, and investigated the effect of CE-WIB801C on collagen-induced human platelet aggregation. CE-WIB801C dose-dependently inhibited collagen-induced platelet aggregation, and its IC50 value was 175 microg/ml. CE-WIB801C increased cAMP level more than cGMP level, but inhibited collagen-elevated [Ca2+]i mobilization and thromboxane A2 (TXA2) production. cAMP-dependent protein kinase (A-kinase) inhibitor Rp-8-Br-cAMPS increased the CE-WIB801C-downregulated [Ca2+]i level in a dose dependent manner, and strongly inhibited CE-WIB801C-induced inositol 1, 4, 5-trisphosphate receptor (IP3R) phosphorylation. These results suggest that the inhibition of [Ca2+]i mobilization by CE-WIB801C is resulted from the cAMP/A-kinase-dependent phosphorylation of IP3R. CE-WIB801C suppressed TXA2 production, but did not inhibit the activities of cyclooxygenase-1 (COX-1) and TXA2 synthase (TXAS). These results suggest that the inhibition of TXA2 production by WIB801C is not resulted from the direct inhibition of COX-1 and TXAS. In this study, we demonstrate that CE-WIB801C with cAMP-dependent Ca2+-antagonistic antiplatelet effects may have preventive or therapeutic potential for platelet aggregation-mediated diseases, such as thrombosis, myocardial infarction, atherosclerosis, and ischemic cerebrovascular disease.

Three Cases of Diphyllobothrium nihonkaiense Infection in Korea

Until 2012, a total of 48 cases of diphyllobothriasis had been reported in Korea, all of which were morphologically identified as Diphyllobothrium latum. However, some of these specimens were analyzed by nucleotide sequencing of the mitochondrial cox1 gene, which showed that all were D. nihonkaiense, not D. latum. After that, 3 further cases of diphyllobothriasis were confirmed as D. nihonkaiense. In the present study, 3 new cases of D. nihonkaiense were detected from 2011 through 2013. The hosts were infected through consumption of salmonid fishes, such as the trout or salmon, and 2 of them experienced severe diarrhea prior to proglottid passage. All of the tapeworms were confirmed to be D. nihonkaiense by genetic identification. This proved again that most diphyllobothriasis in Korea have been caused by D. nihonkaiense.