A novel anti-inflammatory treatment for bradykinin-induced sore throat or pharyngitis.

The aim of this study was to systematically review whether concurrent treatment with an SSRI and low-dose ASA increases the risk of bleeding compared with treatment with an SSRI alone or ASA alone. Medline, Embase, the Cochrane Library, PsycINFO and Web of Science (from database inception to January 2023) were searched according to PICO: P = patients on treatment with an SSRI and/or low-dose ASA; I = intervention: SSRI + ASA; C = comparison: ASA or SSRI alone; O = outcomes: bleeding/major bleeding. The included articles were assessed using checklists. Studies without major risk of bias formed the basis for the conclusions. Extracted data were pooled using random-effects meta-analyses. Certainty of evidence was assessed according to GRADE. Twenty-four studies met the PICO and were included. One randomized and six nonrandomized studies were assessed not to have major risk of bias. Regarding SSRI + ASA vs. ASA only, the pooled hazard ratio of three nonrandomized studies (n = 38 467) was 1.37 (95% confidence interval: 1.10; 1.70; I2= 0%), and the pooled odds ratio of two nonrandomized studies (n = 28296) was 0.95 (0.77; 1.19; I2= 0%). Regarding SSRI + ASA vs. SSRI only, the randomized controlled trial (n = 1048) reported a hazard ratio of 1.82 (0.66; 5.02), the hazard ratio being 1.60 (1.24; 2.06) for ASA vs. placebo in patients without SSRI treatment; and one nonrandomized controlled study (n = 18 920) reported an incidence rate ratio of 1.03 (0.96; 1.12). The compiled evidence was too uncertain to support an interaction when an SSRI is added to low-dose ASA. Low-dose ASA added to an SSRI may imply an increased risk of bleeding primarily attributable to the initiation of ASA.

We investigated the inhibitory effects of black rice (cv. LK1-3-6-12-1-1) bran against 12-O-tetradecanolylphorbol-13-acetate (TPA)-induced skin edema and 2,4-dinitrofluorobenzene (DNFB)-induced allergic contact dermatitis (ACD) in inflammatory mouse models. We also determined the effects of the bran extract on the following biomarkers: pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), eicosanoids leukotriene B4 (LTB4), and prostaglandin E2 (PGE2). Topical application of TPA to ears of CD-1 mice induced inflammation accompanied with substantial increase in TNF-α, IL-1β, IL-6, LTB4, and PGE2 levels and an elevation in intercellular adhesion molecule-1 (ICAM-1) gene expressions in ear skin tissues. Intraperitoneal injection of black rice bran extract prior to TPA application in mice significantly suppressed TPA-induced inflammation (edema) and induced a marked decrease in the production of TNF-α, IL-1β, IL-6, and LTB4. Feeding mice a standard diet with added 10% black rice bran also significantly suppressed DNFB-induced allergic contact dermatitis on the skin of the mice. By contrast, a nonpigmented brown rice bran extract did not inhibit the TPA-induced edema and failed to significantly suppress production of pro-inflammatory biomarkers (mediators). These in vivo findings further demonstrate the potential value of black rice bran as an anti-inflammatory and antiallergic food ingredient and possibly also as a therapeutic agent for the treatment and prevention of diseases associated with chronic inflammation.

Tea has been shown to possess several health beneficial properties primarily due to its polyphenolic content. The major polyphenolic compounds in black tea leaves are theaflavins (TFs) formed by oxidative coupling of catechins in tea leaves during its processing. In this paper, we report the characterization of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear inflammatory model and the inhibitory effects of major black tea TFs derivatives on this inflammation. In addition, the effect on inflammatory biomarkers, such as proinflammatory cytokines and arachidonic acid metabolites, are reported as well. A single topical application of TPA to ears of CD-1 mice induced a time- and dose-dependent increase in edema as well as formation of proinflammatory cytokine proteins interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) in mouse ears. A single topical application of equimolar of black tea constituents (TF, theaflavin-3-gallate, theaflavin-3'-gallate, and theaflavin-3,3'-digallate) strongly inhibited TPA-induced edema of mouse ears. Application of TFs mixture to mouse ears 20 min prior to each TPA application once a day for 4 days inhibited TPA-induced persistent inflammation, as well as TPA-induced increase in IL-1beta and IL-6 protein levels. TFs also inhibited arachidonic acid (AA) metabolism via both cyclooxygenase (COX) and lipoxygenase pathways. This observation was substantiated by decreased amounts of AA metabolites prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) levels. Combined application of TF and sulindac, a nonsteroidal anti-inflammatory drug resulted a significant synergetic anti-inflammatory effect. Oral administration of TFs or the hot water extract of black tea leaves also significantly inhibited TPA-induced edema in mouse ears. In conclusion, proinflammatory cytokines, IL-1beta and IL-6, as well as the intermediated metabolites of AA, PGE2, and LTB4 are good biomarkers for inflammation. Black tea constituents, TF and its derivatives, had strongly anti-inflammatory activity in vivo which may be due to their ability to inhibit AA metabolism via lipoxygenase and COX pathways.

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To observe the effects of moxibustion on the contents of leukotriene B4 (LTB4), interleukin-17 (IL-17), tumor necrosis factor-α (TNF-α) and matrix metalloproteinase -9 (MMP-9) in serum, and explore the protection mechanisms of moxibustion in the patients with rheumatoid arthritis (RA). A total of 64 patients with RA were randomly divided into treatment group (n=31) and control group (n=33). The patients in the control group were treated with conventional medication for consecutive 5 weeks. Based on the treatment in the control group, the patients in the treatment group were treated with moxibustion at bilateral Shenshu (BL23), Zusanli (ST36) and Ashi points, 3 times a week, for consecutive 5 weeks. Separately, the visual analogue scale (VAS) score, morning stiffness score, the number of tender joints, the number of swollen joints, the score of the disease activity score of 28 joints (DAS28) were observed; the contents of rheumatoid factor (RF), erythrocyte sedimentation rate (ESR) and C-reative protein (CRP) in serum were determined by biochemical method; and the contents of LTB4, IL-17, TNF-α and MMP-9 in serum were detected by using ELISA before and after treatment in the patients of both groups. After treatment, VAS score, morning stiffness score, the number of tender joints, the number of swollen joints, DAS28 score, the contents of serum RF in both groups, and contents of serum CRP, ESR, LTB4, IL-17, TNF-α and MMP-9 in the treatment group were significantly reduced when compared with those before treatment (P<0.01, P<0.05). After treatment, VAS score, morning stiffness score, the number of tender joints, the number of swollen joints, DAS28 score, and the levels of LTB4, IL-17 and MMP-9 in serum were obviously lower in the treatment group when compared with the control group (P<0.01, P<0.05). In the treatment group, the changes before and after treatment in the levels of LTB4, IL-17 and TNF-α were positively correlated with that of MMP-9 (P<0.05, r>0). Moxibustion at BL23 and ST36 combined with conventional medication significantly relieves joint pain and reduce disease activity in RA patients, which may be related to the modulation of LTB4, IL-17 and MMP-9 by moxibustion.

Cutaneous T-cell lymphoma (CTCL) is a spectrum of disease of unknown etiology defined by infiltrates of activated and malignant T cells in the skin. In working with blood from CTCL patients, we noticed frequent activation of neutrophils; therefore, we tested the hypothesis that neutrophils are activated in CTCL subjects compared with normal healthy controls. Using peripheral blood of 44 subjects with CTCL and 15 normal controls, we examined three measures of neutrophil activation. These are the presence of neutrophils of reduced buoyant density, the presence of primed neutrophils in a stimulated chemiluminescence assay, and changes in surface markers by flow cytometry. In addition, we tested plasma interleukin-8 (IL-8) and leukotriene B4 (LTB4) levels using ELISA. A significantly larger fraction of hypodense neutrophils was observed in CTCL subjects compared with normals (10.6 +/- 1.7% versus 1.5 +/- 0.4%). Stimulated chemiluminescence was also significantly increased in CTCL, and analysis of neutrophil surface markers using flow cytometry showed significantly increased CD11b and CD66b and decreased CD62L, consistent with neutrophil activation. These changes were present even in early stages of CTCL. We further found that plasma IL-8 and LTB4 levels are elevated in CTCL, which could form a feedback loop contributing to disease pathophysiology. CTCL is associated with systemic neutrophil activation, even in early disease, and a feedback loop between neutrophils and T cells mediated by IL-8 and LTB4 is a potential contribution to the pathophysiology of CTCL.

Low dose acetyl salicylic acid in severe preeclampsia

Prognostic Factors in Arthrocentesis of the Temporomandibular Joint: Comparison of Bradykinin, Leukotriene B4, Prostaglandin E2, and Substance P Level in Synovial Fluid Between Successful and Unsuccessful Cases

Substantial platelet inhibition was observed 3 days after a single administration of acetylsalicylic acid 81mg to healthy volunteers. Here we investigate prostaglandin E2 (PGE2 ) antrum concentrations and gastrointestinal symptoms in two treatment groups: one receiving losartan and acetylsalicylic acid every day and the other receiving losartan every day and acetylsalicylic acid every 3 days. Twenty-eight healthy volunteers from both sexes received either 50mg losartan and acetylsalicylic acid 81mg daily or 50mg losartan and acetylsalicylic acid 81 every 3 days with placebo on the other days. Therapy was delivered for 30 days for both groups. Gastric endoscopy was performed before and after treatment period. Biopsies were collected for PGE2 quantification. Platelet function tests were carried out before and during treatment and TXB2 release on platelet rich plasma was measured. The every 3 day low-dose acetylsalicylic acid regimen produced complete inhibition of platelet aggregation compared to the daily treatment. Thromboxane B2 release was substantially abolished for both groups during treatment. There was no significant difference on the endoscopic score of both treatment groups after the 30-day treatment (P= .215). There was over 50% suppression of antrum PGE2 content on volunteers receiving acetylsalicylic acid daily (P= .0016), while for the every 3 day dose regimen there was no significant difference between pre and post-treatment antrum PGE2 dosages (P= .4193). Since PGE2 is involved in gastric healing, we understand that this new approach could be safer and as efficient as the standard daily therapy on a long-term basis.

UVB Radiation Induces Apoptosis in Keratinocytes by Activating a Pathway Linked to “BLT2-Reactive Oxygen Species”

The peroxisome proliferator-activated receptor system is exciting much interest as a novel point of therapeutic intervention in inflammation. Here, the effect of a peroxisome proliferator-activated receptor alpha agonist, [4-chloro-6-(2,3-xylidine)-pyrimidinylthio]acetic acid (Wy14,643), was examined in arachidonic acid-induced murine ear inflammation. 3-[1-(4-Chlorobenzyl)-3-t-butyl-thio-5-isopropylindol-2-yl]-2,2-dimethylpropanoic acid (MK886, a 5-lipoxygenase inhibitor) and indomethacin (a cyclo-oxygenase inhibitor) were used as reference compounds. Wy14,643 dose dependently inhibited ear swelling and polymorphonuclear leukocyte influx, as did MK886, associated with reduced tissue leukotriene B4 but not prostaglandin E2 levels. Unlike MK886, Wy14,643 did not inhibit ex vivo leukotriene B4 production. However, Wy14,643, but not MK886, induced peroxisomal enzyme activity. Indomethacin was less effective, though tissue prostaglandin E2 but not leukotriene B4 levels were reduced. Again, unlike indomethacin, Wy14,643 did not reduce ex vivo prostaglandin E2 production. However, indomethacin did increase peroxisomal enzyme activity but to a lesser extent than Wy14,643. This study demonstrates that peroxisome proliferator-activated receptor alpha activation can inhibit arachidonic acid-induced inflammation in part by enhancing degradation of leukotriene B4.

We have examined the effects of black tea constituents, theaflavin mixture (TFs), on 12-O-tetradecanoylphorbol-13-acetate-induced inflammation, up-expression of proinflammatory cytokines, interleukin-1β (IL-1β) and interleukin-6 (IL-6) protein levels and formation of prostaglandin E2 (PGE2 ) and leukotriene B4 (LTB4 ) levels in ears of CD-1 mouse as well as on spontaneous colorectal carcinogenesis in Min (Apc+/-) mice. Two doses of TFs, 0.18 and 0.71 mg, were topically applied to mice ears twice a day for 3.5 days (7 treatments) 20 mins prior to each TPA (0.4 nmol) treatment. These doses of TFs inhibited TPA-induced a) inflammation by 74 and 97%, b) up-expression of IL-1β protein levels by 93 and 99%, and c) up-expression of IL-6 protein levels by 58 and 99%, respectively. In these experiments, TFs (0.18 mg or 0.71 mg) also inhibited TPA induced formation of PGE2 by 27-100% and LTB4 by 92-100%. In addition, oral administration of 0.2% or 0.4% TFs (28%) enriched black tea extract in drinking water as sole source of drinking fluid to female Min (Apc+/-) mice for 10 weeks inhibited the formation of the numbers of colorectal tumors per mouse by 39 or 29%, respectively. The percentage of mice bearing colorectal tumors was also inhibited by 39 or 29%, respectively. Furthermore, in these mice there was a reduction in the formation of the number of small intestinal tumors per mouse by 39 or 29% respectively.

The local and systemic release of thromboxane A2, prostaglandin I2, leukotriene B4 (LTB4), tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and interleukin-8 (IL-8) were studied before and after operation in 29 patients with acute and 22 with chronic posttraumatic osteomyelitis. Twenty patients without osteomyelitis, who underwent operations for fractures of the lower extremities, served as controls. Blood and tissue samples from the osteomyelitic and control groups were collected under defined conditions and mediators were determined by radioimmunoassay (thromboxane B2, 6-keto-prostaglandin F1 alpha, LTB4) or by enzyme-linked immunosorbent assay (TNF-alpha, IL-1 beta, and IL-8). In addition, common parameters (leukocyte count, C-reactive protein, temperature) were measured. The best correlation with acute disease activity was given by TNF-alpha, IL-6, IL-8, and LTB4. Plasma levels of these mediators in acute osteomyelitis were significantly increased compared to chronic osteomyelitis and to controls, respectively. Tissue samples from osteomyelitic focus showed significantly increased levels for IL-8, IL-6, TNF-alpha, IL-1 beta, and LTB4 in acute osteomyelitis, whereas the values for TxB2 and 6-keto-prostaglandin F1 alpha were only slightly increased compared to the chronic osteomyelitis group. This study describes the local and systemic liberation of various mediators in acute and chronic posttraumatic osteomyelitis in detail for the first time and provides data for pre- and postoperative monitoring of disease activity and demonstrates new pathogenetic and therapeutic aspects of bone modulation in osteomyelitis.

Antiplatelet therapy using low dose acetylsalicylic acid (ASA) is routinely recommended in patients undergoing surgical or endovascular treatment of carotid artery disease. Despite this treatment, a significant proportion of postoperative complications may result from inadequate response to antiplatelet therapy which may contribute to the development of unstable plaques. Assessment of correlation between ASA resistance and the presence of unstable carotid plaque in patients after carotid endarterectomy. We studied 66 patients (27 women and 39 men) aged 41-80 years who were operated for carotid stenosis. All patients received ASA (75 mg once daily) in the pre- and perioperative period. Measurements of platelet reactivity were performed using the PFA-100 platelet analyser at the second day after the operation. Plaque stability was evaluated using a computer analysis system based on the greyscale median method. The patients were divided into two groups, showing good response to ASA or ASA-resistant. ASA resistance was identified in 19 (32%) patients. In multivariate logistic regression analysis, unstable plaque showed a borderline correlation with ASA resistance (p = 0.051). 1. Prevalence of increased platelet reactivity despite ASA treatment (ASA resistance) in patients treated surgically for carotid artery disease is high, suggesting a possibility of ineffective antiplatelet therapy. 2. A modest correlation between abnormal platelet response during treatment with ASA and the presence of unstable plaques suggests that these two phenomena may coexist but we were unable to show a clear association between them.

The present study was designed to investigate the anti-inflammatory activity and mechanism of a lipid extract from hard-shelled mussel (Mytilus coruscus) on adjuvant-induced (AIA) and collagen-induced arthritis (CIA) in rats. AIA and CIA rats that received hard-shelled mussel lipid extract (HMLE group) at a dose of 100 mg/kg demonstrated significantly lower paw swelling and arthritic index, but higher body weight gain than those which received olive oil (control group). Similar results were found in arthritic rats that received New Zealand green-lipped mussel lipid extract (GMLE) at the same dosage. The levels of leukotriene B4 (LTB4), prostaglandin E2 (PGE2), thromboxane B2 (TXB2) in the serum, and interleukin-1β (IL-1β), IL-6, interferon-γ (INF-γ), tumor necrosis factor-α (TNF-α) in the ankle joint synovial fluids of HMLE group rats were significantly lower than those of control group. However, the levels of IL-4 and IL-10 in HMLE group rats were significantly higher than those in the control group. Decreased mRNA expressions of matrix metalloproteinase 1 (MMP1) and MMP13, but increased tissue inhibitor of metalloproteinase 1 (TIMP1) were observed in the knee joint synovium tissues of HMLE group rats when compared with the control group. No hepatotoxicity was observed in both HMLE and GMLE group rats. The present results indicated that HMLE had a similarly strong anti-inflammatory activity as GMLE. Such a strong efficacy could result from the suppression of inflammatory mediators (LTB4, PGE2, TXB2), pro-inflammatory cytokines (IL-1β, IL-6, INF-γ, TNF-α) and MMPs (MMP1, MMP13), and the promotion of anti-inflammatory cytokines (IL-4, IL-10) and TIMPs (TIMP1) productions.