The role of magnetic resonance imaging and magnetic resonance sialography in the evaluation of salivary sialolithiasis : radiologic-endoscopic correlation

Purpose: To evaluate the role of magnetic resonance imaging (MRI) and MR sialography in salivary gland calculi in correlation with sialendoscopy. Material and methods: In this prospective study, pre-therapeutic MRI was performed for patients with clinically suspected sialolithiasis. In addition, sialendoscopy with or without surgery was performed. The detectability, number, size, and location of calculi (distance of obstruction from the ostium and masseter line) and the condition of the main duct at MRI were reported. Agreement between the 2 readers was confirmed for all MRI findings. Data regarding the detectability, number, and size of calculi were correlated with endoscopy. Results: There was excellent agreement between the 2 readers regarding the detection and number of calculi at MR sialography (κ = 1, p < 0.001). As regards MRI measurements, excellent interclass correlation was found between the 2 readers regarding size of calculi, distance of calculi from the ostium, and distance from the masseter line (κ = 0.98, 0.98, 0.97, respectively; p < 0.001). In correlation with sialendoscopy, MRI was false negative in 1 patient, and it missed 1 calculus in 3 patients with multiple calculi. There was no statistically significant difference between the size of calculi detected by MRI and true size of calculi retrieved by sialendoscopy. Conclusion: MR sialography is an accurate modality for diagnosis of the presence, size, and location of sialolithiasis and offers accurate ductal mapping for sialendoscopists

Stimulation of the histamine 4 receptor with 4-methylhistamine modulates the effects of chronic stress on the Th1/Th2 cytokine balance.

Alterations to the immune system caused by stress have been considered to markedly increase the risk for immune-related diseases such as cancer and autoimmune disorders. We investigated the potential anti-stress effects of the histamine 4 receptor (H4R) agonist, 4-methylhistamine (4-MeH), in a murine stress model. Mice were placed in 50ml conical centrifuge tubes for 12h followed by a 12h rest. The effects of treatment with 4-MeH (30mg/kg, i.p., twice daily) for 2 days were assessed. At 2 days after physical restraint, mice were sacrificed and tissues harvested. We evaluated the effects of 4-MeH treatment on CD4(+) T cell production, and intracellular IFN-γ and IL-4 expression in these cells. We also assessed IL-1β, IFN-γ, TNF-α, and IL-4 mRNA expression as well as IFN-γ, TNF-α, GITR, Ox40 and IL-4 protein expression in the spleen. The results showed that 4-MeH treatment of stressed mice results in a substantial increase in the CD4(+) T cells as well as in IFN-γ production by these cells. Compared to both untreated and stressed controls. In contrast, IL-4 expression decreased significantly following 4-MeH treatment of mice. Moreover, stimulation of the H4R resulted in up-regulated expression of IL-1β, IFN-γ and TNF-α mRNAs and decreased the expression of IL-4. Western blot analysis confirmed decreased protein expression of IFN-γ, TNF-α, GITR, Ox40 and increased IL-4 in the SC group and treatment of mice with 4-MeH reversed these effects. Our results confirm the significant impact of chronic stress on T cell function and production of Th1/Th2 mediators H4R

Regulation of TNF-α and NF-κB activation through the JAK/STAT signaling pathway downstream of histamine 4 receptor in a rat model of LPS-induced joint inflammation.

Histamine 4 receptor (H4R) is a novel target for the pharmacological modulation of histamine-mediated immune signals during inflammatory diseases. The purpose of this study was to assess the effects of the H4R agonist 4-methylhistamine dihydrochloride (4-MeH) and antagonist JNJ7777120 (JNJ) in the inflamed rat knee. Animals were fasted for 18h before a single dose of 4-MeH or JNJ (30mg/kg) was administered intraperitoneally (i.p.), both followed by intra-articular (i.a.) injection of LPS 2h later. Blood and synovial fluid were collected after a short incubation period and TNF-α, NF-κB, and IkB-α levels were measured via flow cytometry. Additionally, we assessed the effects of H4R engagement on the expression of IL-1β, TNF-α, and NF-κB mRNAs and the protein levels of TNF-α, NF-κB, JAK-1, and STAT-3 in the inflamed knee tissue. These results revealed increased TNF-α and NF-κB expression and decreased IkB-α levels in both the LPS alone and 4-MeH treated groups in whole blood and synovial fluid. Further, IL-1β, TNF-α, and NF-κB mRNA levels were significantly increased and western blot analysis confirmed increased expression of TNF-α, NF-κB, JAK-1, and STAT-3 in both LPS and 4-MeH treatment groups. Furthermore, these increases were completely inhibited in the inflamed knee tissue of the JNJ-treated group. Thus, the inhibition of inflammatory mediators and signaling pathways by the H4R antagonist JNJ suggests the anti-arthritic importance of this molecule

Naringin attenuates the development of carrageenan-induced acute lung inflammation through inhibition of NF-κb, STAT3 and pro-inflammatory mediators and enhancement of IκBα and anti-inflammatory cytokines

Naringin has been reported to possess diverse pharmacological properties, including anti-arthritic and anti-inflammatory activities. The aim of the present study was to determine the potential anti-inflammatory effect of naringin in a mouse model of carrageenan-induced pleurisy. A single dose of naringin (40 and 80 mg/kg) was administered per oral (p.o.) 1 h before carrageenan (Cg) administration. Pro- and anti-inflammatory cytokines were analysed in pleural fluid. We also assessed the effects of naringin on the expression levels of iNOS, inducible cyclooxygenase isoform (COX-2), ICAM-1, MIP-2, PGE2, STAT3, TGF-β1, nuclear factor kappa B (NF-κB) and inhibitor of kappa B (IκBα) in lung tissue. The histological examinations revealed anti-inflammatory effect of naringin while Cg group deteriorated. Naringin downregulated Th1 and upregulated Th2 cytokines. Western blot analyses revealed increased protein expression of NF-κB, STAT3 and COX-2 and decreased IκBα in response to Cg treatment, which were reversed by the treatment with naringin. In the Cg group, mRNA expression levels of pro-inflammatory mediators upregulated and anti-inflammatory mediators downregulated. Naringin reversed these actions

Design and Synthesis of <i>N</i>‑Arylphthalimides as Inhibitors of Glucocorticoid-Induced TNF Receptor-Related Protein, Proinflammatory Mediators, and Cytokines in Carrageenan-Induced Lung Inflammation

<i>N</i>-Arylphthalimides (<b>1</b>–<b>10P</b>) derived from thalidomide by insertion of hydrophobic groups were evaluated for anti-inflammatory activity, and (4-(1,3-dioxo-1,3-dihydro-2<i>H</i>-isoindol-2-yl)-<i>N</i>′-[(4-ethoxyphenyl)­methylidene]­benzohydrazide <b>6P</b> was identified as a promising anti-inflammatory agent. Further testing confirmed that compared with the control, <b>6P</b> treatment resulted in a considerable decrease in CD4⁺, NF-κB p65⁺, TNF-α⁺, IL-6⁺, GITR⁺, and IL-17⁺ cell populations and an increase in the Foxp3⁺, CD4⁺Foxp3⁺, and IκBα⁺ populations in whole blood and pleural fluid of a mouse model of lung inflammation. Moreover, treatment with compound <b>6P</b> decreased the proteins associated with inflammation including TNF-α, IL-6, IL-17, GITR, NF-κB, COX-2, STAT-3, and iNOS and increased the anti-inflammatory mediators such as IL-10 and IL-4. Further, histopathological examination confirmed the potent anti-inflammatory effects of compound <b>6P</b>. Thus, the <i>N</i>-arylphthalimide derivative <b>6P</b> acts as a potent anti-inflammatory agent in the carrageenan-induced lung inflammation model, suggesting that this compound may be useful for the treatment of inflammation in a clinical setting