The effectiveness of anti-interleukin-1 therapy on subclinical inflammation parameters during the attack-free period in familial Mediterranean fever patients: A case-control study.

BACKGROUND: : Anti IL-1 therapy is useful in suppressing attacks in FMF patients with colchicine resistance, however, it is not certain whether subclinical inflammation can sufficiently be inhibited with anti-IL-1 therapy in FMF patients with amyloidosis. METHODS: Forty-six FMF patients receiving anti-interleukin-1 therapy and 36 healthy control patients were compared in terms of laboratory parameters. Also, FMF patients were further divided into two groups; those with amyloidosis and those without it, and these subgroups were compared to each other in terms of clinical and laboratory findings. RESULTS: In comparison between the FMF and healthy control groups, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, and red cell distribution width (RDW) level were detected to be higher and hemoglobin level lower in the patient group. Within the FMF patient group, the ESR, CRP, fibrinogen, RDW, and NLR values were significantly higher in the subgroup with amyloidosis in comparison to the subgroup without amyloidosis. DISCUSSION: Anti-interleukin-1 therapy could not fully suppress the subclinical inflammatory parameters when compared to healthy individuals.

The effectiveness of anti-interleukin-1 therapy on subclinical inflammation parameters during the attack-free period in familial Mediterranean fever patients: A case-control study.

Background/aim: Anti IL-1 therapy is useful in suppressing attacks in FMF patients with colchicine resistance, however, it is not certain whether subclinical inflammation can sufficiently be inhibited with anti-IL-1 therapy in FMF patients with amyloidosis. Materials and methods: Forty-six FMF patients receiving anti-interleukin-1 therapy and 36 healthy control patients were compared in terms of laboratory parameters. Also, FMF patients were further divided into two groups; those with amyloidosis and those without it, and these subgroups were compared to each other in terms of clinical and laboratory findings. Results: In comparison between the FMF and healthy control groups, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, and red cell distribution width (RDW) level were detected to be higher and hemoglobin level lower in the patient group. Within the FMF patient group, the ESR, CRP, fibrinogen, RDW, and NLR values were significantly higher in the subgroup with amyloidosis in comparison to the subgroup without amyloidosis. Conclusion: Anti-interleukin-1 therapy could not fully suppress the subclinical inflammatory parameters when compared to healthy individuals.

[Bilateral idiopathic chondrolysis of the hips - A case report of an adolescent patient]. / Idiopathische Chondrolyse beider Hüftgelenke ­ Fallbericht bei einer adoleszenten Patientin.

The diagnosis and treatment of idiopathic chondrolysis of the hips are described in the case of a 12-year-old girl. The patient presented with intermittent pain and extreme dysfunction of both hips. After clinical examination and pelvic X­ray, MRI showed the typical changes of idiopathic chondrolysis. Purely conservative treatment with systematic physiotherapy and regular application of a non-steroidal anti-inflammatory drug produced a good clinical result.

Synthesis and biological evaluation of pyridine-linked indanone derivatives: Potential agents for inflammatory bowel disease.

A series of pyridine-linked indanone derivatives were designed and synthesized to discover new small molecules for the treatment of inflammatory bowel disease (IBD). Compounds 5b and 5d exhibited strongest inhibitory activity against TNF-α-induced monocyte adhesion to colon epithelial cells (an in vitro model of colitis). In TNBS (2,4,6-trinitrobenzenesulfonic acid)-induced rat colitis model, oral administration of the compounds 5b and 5d ameliorated colitis with significant recovery in altered expressions of E-cadherin, TNF-α and IL-1ß expressions, indicating 5b and 5d as potential agents for therapeutics development against IBD.

Wogonin induces eosinophil apoptosis and attenuates allergic airway inflammation.

RATIONALE: Eosinophils are key effector cells in allergic diseases, including allergic rhinitis, eczema, and asthma. Their tissue presence is regulated by both recruitment and increased longevity at inflamed sites. OBJECTIVES: To investigate the ability of the flavone wogonin to induce eosinophil apoptosis in vitro and attenuate eosinophil-dominant allergic inflammation in vivo in mice. METHODS: Human and mouse eosinophil apoptosis in response to wogonin was investigated by cellular morphology, flow cytometry, mitochondrial membrane permeability, and pharmacological caspase inhibition. Allergic lung inflammation was modeled in mice sensitized and challenged with ovalbumin. Bronchoalveolar lavage (BAL) and lung tissue were examined for inflammation, mucus production, and inflammatory mediator production. Airway hyperresponsiveness to aerosolized methacholine was measured. MEASUREMENTS AND MAIN RESULTS: Wogonin induced time- and concentration-dependent human and mouse eosinophil apoptosis in vitro. Wogonin-induced eosinophil apoptosis occurred with activation of caspase-3 and was inhibited by pharmacological caspase inhibition. Wogonin administration attenuated allergic airway inflammation in vivo with reductions in BAL and interstitial eosinophil numbers, increased eosinophil apoptosis, reduced airway mucus production, and attenuated airway hyperresponsiveness. This wogonin-induced reduction in allergic airway inflammation was prevented by concurrent caspase inhibition in vivo. CONCLUSIONS: Wogonin induces eosinophil apoptosis and attenuates allergic airway inflammation, suggesting that it has therapeutic potential for the treatment of allergic inflammation in humans.

Ibuprofen therapy resulted in significantly decreased tissue bacillary loads and increased survival in a new murine experimental model of active tuberculosis.

C3HeB/FeJ mice infected with Mycobacterium tuberculosis were used in an experimental animal model mimicking active tuberculosis in humans to evaluate the effect of antiinflammatory agents. No other treatment but ibuprofen was given, and it was administered when the animals' health started to deteriorate. Animals treated with ibuprofen had statistically significant decreases in the size and number of lung lesions, decreases in the bacillary load, and improvements in survival, compared with findings for untreated animals. Because antiinflammatory agents are already on the market, further clinical trials should be done to evaluate this effect in humans as soon as possible, to determine their suitability as coadjuvant tuberculosis treatment.

Ameliorative Effect of Aqueous and Hydroalcoholic Extracts of Scrophularia striata Boiss. on Murine Model of Experimental Colitis.

Background: Scrophularia striata Boiss. (S. striata) is a flowering plant with several therapeutic properties including antiinflammatory, antioxidant, antimicrobial, and wound-healing activity. Regarding the side effects of drugs conventionally used for inflammatory bowel disease (IBD) treatment, we investigated the anticolitis properties of aqueous (SSAE) and hydroalcoholic (SSHE) extracts of S. striata on experimental colitis. Materials and Methods: The colitis was induced using acetic acid (3%) and 2 h before ulcer induction, each group of rats received orally three doses (150, 300, and 600 mg/kg, p.o.) of SSAE or SSHE for the next 5 days. Dexamethasone (1 mg/kg, i.p.) and mesalazine (100 mg/kg, p.o.) were used as reference drugs. Different parameters including weight of colon/height, ulcer index, total colitis index, levels of myeloperoxidase (MPO) and malondialdehyde (MDA) were investigated. Results: Total phenolic contents were 4.3 ± 0.2 and 7.1 ± 0.4 mg/g equivalent to gallic acid for SSAE and SSHE respectively. Three applied doses of SSHE and the highest dose of SSAE (600 mg/kg) could reduce all the macroscopic and pathologic indices of colitis and the levels of MPO and MDA. Two lesser doses of SSAE (150, 300 mg/kg) however, couldn't diminish the histopathologic features of colitis and the values of MPO and MDA. Conclusions: S. striata, especially SSHE, which also contained more phenolic compounds, had an ameliorating effect on ulcerative colitis and possibly exerts this effect through its antioxidant, antiinflammatory and wound healing properties. Further investigations are required to introduce this plant as a novel alternative herbal drug for colitis treatment.

Spectrophotometric Analysis and Determination of Anti-inflammatory Effect of Punica granatum and Woodfordia fruticosa in Subjects With Chronic Periodontitis - A Randomized Controlled Clinical Trial.

INTRODUCTION: Long-term use of chemical plaque control methods has led to adverse effects. In the current scenario, herbal mouthwashes have adequately remediated periodontal disease. Moreover, in the salivary interactome, biomarkers such as salivary amylase, a key protein secreted in the saliva, have been immensely useful in detecting the progression of periodontal disease. Therefore, we aimed to determine the anti-inflammatory effect of ethanolic crude extracts of Woodordiafruticosa leaf and Punicagranatum peel and to estimate salivary amylase levels in subjects diagnosed with chronic periodontitis. METHODOLOGY: Ethanolic extracts of both plants were prepared using the soxhlet extraction method, and the obtained metabolites were confirmed by thin-layer chromatography. After a mouthwash was prepared, 100 subjects were randomly divided into two groups. Group I received Punica peel (Pgp) mouthwash, and Group II received Woodfordialeaf (Wfl). Clinical parameters such as probing depth and clinical attachment loss were recorded to determine the grades of periodontitis. Unstimulated whole saliva was collected, and amylase levels were analyzed at three-time intervals using spectrophotometric assay. RESULTS: For both groups, the mean reduction in salivary amylase levels was calculated at baseline after 1 hour and 1 week of using the mouthwash. A statistically highly significant reduction was seen with (p=0.000*) at the 1-hr interval in Group I. CONCLUSION: The anti-inflammatory effect was more effective with Pgp mouthwash when compared to Wfl mouthwash.

Monitoring therapy in anterior necrotizing scleritis with inflammation with anterior segment optical coherence tomography.

INTRODUCTION: Early diagnosis and initiation of immunosuppression can prevent the necessity of surgical intervention in necrotizing scleritis with inflammation and lowers the risk of perforation and loss of vision. However, clinical signs for early diagnosis and methods for monitoring response to immunosuppressive therapy are missing. METHODS: Here, we present a case of necrotizing scleritis with inflammation where avascular plaques precede scleral defects. We use slit lamp imaging and anterior segment optical coherence tomography to evaluate evolution lesions depth and impact on scleral structure. RESULTS: The patient presented 5 months after detection of avascular plaques with a new scleral ulcer of the left eye. After 3-day-administration of i.v. corticosteroids anterior segment optical coherence tomography showed progressive scleral thickening. The patient was therefore spared surgical intervention and discharged resulting in complete remission under decreasing doses of oral corticosteroids. CONCLUSIONS: Avascular plaques can precede necrotizing scleritis with inflammation by several months and may therefore qualify as early clinical signs. Anterior segment optical coherence tomography enables objective evaluation of scleral structure for making rational decisions about surgical intervention.

Natural COX-2 Inhibitors as Promising Anti-inflammatory Agents: An Update.

COX-2, a key enzyme that catalyzed the rate-limiting steps in the conversion of arachidonic acid to prostaglandins, played a pivotal role in the inflammatory process. Different from other family members, COX-2 was barely detectable in normal physiological conditions and highly inducible during the acute inflammatory response of human bodies to injuries or infections. Therefore, the therapeutic utilization of selective COX-2 inhibitors has already been considered as an effective approach for the treatment of inflammation with diminished side effects. Currently, both traditional and newer NSAIDs are the commonly prescribed medications that treat inflammatory diseases by targeting COX-2. However, due to the cardiovascular side-effects of the NSAIDs, finding reasonable alternatives for these frequently prescribed medicines are a hot spot in medicinal chemistry research. Naturallyoccurring compounds have been reported to inhibit COX-2, thereby possessing beneficial effects against inflammation and certain cell injury. The review mainly concentrated on recently identified natural products and derivatives as COX-2 inhibitors, the characteristics of their structural core scaffolds, their anti-inflammatory effects, molecular mechanisms for enzymatic inhibition, and related structure-activity relationships. According to the structural features, the natural COX-2 inhibitors were mainly divided into the following categories: natural phenols, flavonoids, stilbenes, terpenoids, quinones, and alkaloids. Apart from the anti-inflammatory activities, a few dietary COX-2 inhibitors from nature origin also exhibited chemopreventive effects by targeting COX-2-mediated carcinogenesis. The utilization of these natural remedies in future cancer prevention was also discussed. In all, the survey on the characterized COX-2 inhibitors from natural sources paves the way for the further development of more potent and selective COX-2 inhibitors in the future.

[Allergy and intolerance to nonsteroidal anti-inflammatory drugs in children]. / Alergia e intolerancia a antiinflamatorios no esteroideos en pediatría.

Nonsteroidal anti-inflammatory drugs are widely prescribed in children. They are the second cause of drug's reactions in pediatrics after beta-lactam antibiotics, however only a part of them are hypersensitivity reactions. The prevalence of these reactions to nonsteroidal anti-inflammatory drugs in children is 0.3 %, increasing to 5 % in asthmatics. The different physiopathological mechanisms involved (inhibition of cyclooxygenase, immunoglobulin E-mediated hypersensitivity, reactive T lymphocytes and/or disturbance of innate immunity) will cause different clinical entities with diverse symptoms. The confusion between the common symptoms of a viral infection and a hypersensitivity reaction, and the variability of the clinical presentations make diagnosis a real challenge. A detailed clinical history, laboratory, skin and controlled provocation tests will provide strategies for each patient, without labeling a child who is not an allergic one, or taking unnecessary risks with those who are sensitized.

Los antiinflamatorios no esteroideos son ampliamente recetados en niños. Constituyen la segunda causa de reacciones a medicamentos en pediatría después de los antibióticos betalactámicos; sin embargo, solo una parte de estas son reacciones de hipersensibilidad. La prevalencia de dichas reacciones a antiinflamatorios no esteroideos en niños es del 0,3 % y aumenta al 5 % en asmáticos. Los mecanismos fisiopatológicos involucrados (inhibición de la ciclooxigenasa, hipersensibilidad mediada por inmunoglobulina E, linfocitos T reactivos y/o afectación de la inmunidad innata) darán lugar a diferentes entidades clínicas con sintomatología dispar. La confusión con síntomas propios de procesos virales y la variabilidad clínica hacen del diagnóstico de certeza un verdadero desafío. Una historia clínica detallada, análisis de laboratorio, pruebas cutáneas y de provocación controlada permitirán definir estrategias para cada paciente en particular sin etiquetar como alérgico a un niño que no lo es ni exponer a riesgos innecesarios a quien está sensibilizado.

Current pharmacological treatments for COVID-19: What's next?

Since December 2019 SARS-Cov-2 was found responsible for the disease COVID-19, which has spread worldwide. No specific therapies/vaccines are yet available for the treatment of COVID-19. Drug repositioning may offer a strategy and a number of drugs have been repurposed, including lopinavir/ritonavir, remdesivir, favipiravir and tocilizumab. This paper describes the main pharmacological properties of such drugs administered to patients with COVID-19, focusing on their antiviral, immune-modulatory and/or anti-inflammatory actions. Where available, data from clinical trials involving patients with COVID-19 are reported. Preliminary clinical trials seem to support their benefit. However, such drugs in COVID-19 patients have peculiar safety profiles. Thus, adequate clinical trials are necessary for these compounds. Nevertheless, while waiting for effective preventive measures i.e. vaccines, many clinical trials on drugs belonging to different therapeutic classes are currently underway. Their results will help us in defining the best way to treat COVID-19 and reducing its symptoms and complications. LINKED ARTICLES: This article is part of a themed issue on The Pharmacology of COVID-19. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.21/issuetoc.

Antinociceptive and anti-inflammatory effects of ginsenoside Rf in a rat model of incisional pain.

BACKGROUND: Ginseng saponin has long been used as a traditional Asian medicine and is known to be effective in treating various kinds of pain. Ginsenoside Rf is one of the biologically active saponins found in ginseng. We evaluated ginsenoside Rf's antinociceptive and anti-inflammatory effects, and its mechanism of action on adrenergic and serotonergic receptors, in an incisional pain model. METHODS: Mechanical hyperalgesia was induced via plantar incision in rats followed by intraperitoneal administration of increasing doses of ginsenoside Rf (vehicle, 0.5 mg/kg, 1 mg/kg, 1.5 mg/kg, and 2 mg/kg). The antinociceptive effect was also compared in a Positive Control Group that received a ketorolac (30 mg/kg) injection, and the Naïve Group, which did not undergo incision. To evaluate the mechanism of action, rats were treated with prazosin (1 mg/kg), yohimbine (2 mg/kg), or ketanserin (1 mg/kg) prior to receiving ginsenoside Rf (1.5 mg/kg). The mechanical withdrawal threshold was measured using von Frey filaments at various time points before and after ginsenoside Rf administration. To evaluate the anti-inflammatory effect, serum interleukin (IL)-1ß, IL-6, and tumor necrotizing factor-α levels were measured. RESULTS: Ginsenoside Rf increased the mechanical withdrawal threshold significantly, with a curvilinear dose-response curve peaking at 1.5 mg/kg. IL-1ß, IL-6, and tumor necrotizing factor-α levels significantly decreased after ginsenoside Rf treatment. Ginsenoside Rf's antinociceptive effect was reduced by yohimbine, but potentiated by prazosin and ketanserin. CONCLUSION: Intraperitoneal ginsenoside Rf has an antinociceptive effect peaking at a dose of 1.5 mg/kg. Anti-inflammatory effects were also detected.

Evaluation of Two Potent and Selective PET Radioligands to Image COX-1 and COX-2 in Rhesus Monkeys.

This study assessed whether the newly developed PET radioligands 11C-PS13 and 11C-MC1 could image constitutive levels of cyclooxygenase (COX)-1 and COX-2, respectively, in rhesus monkeys. Methods: After intravenous injection of either radioligand, 24 whole-body PET scans were performed. To measure enzyme-specific uptake, scans of the 2 radioligands were also performed after administration of a nonradioactive drug preferential for either COX-1 or COX-2. Concurrent venous samples were obtained to measure parent radioligand concentrations. SUVs were calculated from 10 to 90 min. Results:11C-PS13 showed specific uptake in most organs, including spleen, gastrointestinal tract, kidneys, and brain, which was blocked by COX-1, but not COX-2, preferential inhibitors. Specific uptake of 11C-MC1 was not observed in any organ except the ovaries and possibly kidneys. Conclusion: The findings suggest that 11C-PS13 has adequate signal in monkeys to justify its extension to human subjects. In contrast, 11C-MC1 is unlikely to show significant signal in healthy humans, though it may be able to do so in inflammatory conditions.

The Safety and Efficacy of Low-Dose Naltrexone in the Management of Chronic Pain and Inflammation in Multiple Sclerosis, Fibromyalgia, Crohn's Disease, and Other Chronic Pain Disorders.

Chronic inflammatory diseases are complex to treat and have an impact on a large number of patients. Due to the difficulty of treating these diseases and the great impact on quality of life, patients often seek off-label, complimentary, or alternative medicines to gain relief from symptoms. Low-dose naltrexone has been used off-label for treatment of pain and inflammation in multiple sclerosis, Crohn's disease, fibromyalgia, and other diseases. Naltrexone is a mu-opioid receptor antagonist indicated by the U.S. Food and Drug Administration for opioid and alcohol dependence. It is hypothesized that lower than standard doses of naltrexone inhibit cellular proliferation of T and B cells and block Toll-like receptor 4, resulting in an analgesic and antiinflammatory effect. It is the purpose of this review to examine the evidence of the safety, tolerability, and efficacy of low-dose naltrexone for use in chronic pain and inflammatory conditions. Currently, evidence supports the safety and tolerability of low-dose naltrexone in multiple sclerosis, fibromyalgia, and Crohn's disease. Fewer studies support the efficacy of low-dose naltrexone, with most of these focusing on subjective measures such as quality of life or self-reported pain. These studies do demonstrate that low-dose naltrexone has subjective benefits over placebo, but evidence for more objective measures is limited. However, further randomized controlled trials are needed to determine the efficacy of low-dose naltrexone due to insufficient evidence supporting its use in these disease states. This review provides practitioners with the extent of low-dose naltrexone evidence so that they can be cognizant of situations where it may not be the most appropriate therapy.

Prevalence of in-hospital nonsteroidal antiinflammatory drug exposure in patients with a primary diagnosis of heart failure.

AIM: To determine the prevalence of in-hospital nonsteroidal antiinflammatory drug (NSAID) exposure and associated outcomes in patients admitted with a primary diagnosis of heart failure. METHODS: We performed a propensity-matched cohort analysis of patients admitted to Houston Methodist Hospital System with a primary diagnosis of heart failure according to the International Classification of Diseases-9-Clinical Modification (ICD-9-CM) from January 1, 2011 to December 31, 2014. RESULTS: Of the 9742 patients admitted with a primary diagnosis of heart failure, 384 patients (3.9%) were exposed to NSAID. After applying propensity scores we matched 305 NSAID exposed with 915 unexposed patients. Patients with in-hospital NSAID exposure had a longer length of stay (7.0±8.8 days vs 6.1±8.5; P=.003) and increased prevalence of worsening renal function (34.4% vs 27.9%; P=.030). There were not statically significant differences in in-hospital mortality rate or 30-day all-cause readmission rate. CONCLUSION: Exposure to NSAID in patients admitted with a primary diagnosis of heart failure was low but was associated with adverse outcomes including longer length of stay and higher prevalence or worsening renal function.

Obstrucción intestinal por adherencias: un lienzo en blanco en el que el cirujano elige los colores / Intestinal obstruction due to adherences: a blank canvas on which the surgeon chooses the colors

Introducción. La obstrucción intestinal es una patología de alta prevalencia. Su abordaje diagnóstico y terapéutico ha evolucionado acorde con el avance del conocimiento e implementación de la tecnología. El impacto de sus complicaciones obliga a redoblar esfuerzos en pro de lograr una mayor efectividad. Se hizo una aproximación reflexiva al problema, mediante una identificación de los puntos controversiales de interés para el cirujano general. Métodos. Se realizó una búsqueda sistemática de la literatura en varias bases de datos, utilizando dos ecuaciones de búsqueda que emplearon términos seleccionados a partir de los tesauros "Medical Subject Heading" (MeSH) y "Descriptores en Ciencias de la Salud" (DeCS). Resultados. Se recolectaron 43 artículos y a partir de ellos se construyó el texto de revisión. La identificación pronta de los posibles candidatos a cirugía, mediante un esquema diagnóstico y terapéutico, se constituye en una prioridad en el manejo de estos pacientes. De igual manera, se efectúan consideraciones en la toma de decisiones con respecto a la vía quirúrgica, así como recomendaciones técnicas operatorias producto de la experiencia y lo reportado en la literatura. Existen factores propios del cirujano, del contexto y del paciente, que inciden en la resolución del problema. Conclusión. La obstrucción intestinal y sus implicaciones clínicas obligan a una reevaluación constante de su estado del arte y avances en el manejo, tendiente a una búsqueda de oportunidades para impactar favorablemente en su curso clínico. Hay estrategias por implementar, inclusive el manejo laparoscópico en casos seleccionados

Introduction. Intestinal obstruction is a pathology of high prevalence. Its diagnostic and therapeutic approach has evolved according to the progress in knowledge and implementation of technology. The impact of its complications makes it necessary to make the efforts to achieve higher effectiveness. A reflexive approach to the problem is made by identifying the controversial points of interest for the general surgeon. Methods. A systematic literature search was carried out in several databases, using two search equations from the review performed in the thesaurus "Medical Subject Heading" (MeSH) and "Descriptors in Health Sciences" (DeCS). Results. A total of 43 articles were collected using the selected methods and the review text was constructed from them. The early identification of possible candidates for surgery, by means of a diagnostic and therapeutic algorithm, is a priority in the management of these patients. Likewise, considerations are made in decision-making regarding the laparoscopic vs. traditional approach, as well as operative technical recommendations based on experience and what has been reported in the literature. There are factors specific to the surgeon, the context and the patient that influence the resolution of the problem. Conclusion. Intestinal obstruction and its clinical implications require a constant reevaluation of the state of the art and advances in management, tending to search for opportunities to favorably impact its clinical course. There are strategies to be implemented, including laparoscopic management in selected cases

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.

PIN1 inhibition suppresses osteoclast differentiation and inflammatory responses.

Inflammatory responses and osteoclast differentiation play pivotal roles in the pathogenesis of osteolytic bone diseases such as periodontitis. Although overexpression or inhibition of peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 (PIN1) offers a possible therapeutic strategy for chronic inflammatory diseases, the role of PIN1 in periodontal disease is unclear. The aim of the present study was to evaluate PIN1 expression in periodontitis patients as well as the effects of PIN1 inhibition by juglone or PIN1 small-interfering RNA (siRNA) and of PIN1 overexpression using a recombinant adenovirus encoding PIN1 (Ad-PIN1) on the inflammatory response and osteoclastic differentiation in lipopolysaccharide (LPS)- and nicotine-stimulated human periodontal ligament cells (PDLCs). PIN1 was up-regulated in chronically inflamed PDLCs from periodontitis patients and in LPS- and nicotine-exposed PDLCs. Inhibition of PIN1 by juglone or knockdown of PIN1 gene expression by siRNA markedly attenuated LPS- and nicotine-stimulated prostaglandin E2 (PGE2) and nitric oxide (NO) production, as well as cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression, whereas PIN1 overexpression by Ad-PIN1 increased it. LPS- and nicotine-induced nuclear factor (NF)-κB activation was blocked by juglone and PIN1 siRNA but increased by Ad-PIN1. Conditioned medium prepared from LPS- and nicotine-treated PDLCs increased the number of tartrate-resistant acid phosphatase-stained osteoclasts and osteoclast-specific gene expression. These responses were blocked by PIN1 inhibition and silencing but stimulated by Ad-PIN1. Furthermore, juglone and PIN1 siRNA inhibited LPS- and nicotine-induced osteoclastogenic cytokine expression in PDLCs. This study is the first to demonstrate that PIN1 inhibition exhibits anti-inflammatory effects and blocks osteoclastic differentiation in LPS- and nicotine-treated PDLCs. PIN1 inhibition may be a therapeutic strategy for inflammatory osteolysis in periodontal disease.

Optimal analgesia during major open and laparoscopic abdominal surgery.

Optimal analgesia is a key element of enhanced recovery after surgery (ERAS), not only for humanitarian reasons but also because poorly relieved surgical pain contributes to surgical stress and impairs recovery. A multimodal analgesic approach is advised in order to provide adequate analgesia, reduce opioid consumption, reduce side effects and facilitate the achievement of ERAS milestones. For open surgery, a thoracic epidural for 48 to 72 hours, with regular acetaminophen and antiinflammatories is probably the treatment of choice. For laparoscopic surgery, intrathecal or local anesthesia in the wound combined with regular acetaminophen and antiinflammatory drugs is effective.