Adhesion molecules and their ligands in nasal polyps of aspirin-hypersensitive patients.

BACKGROUND: Chronic inflammation with tissue eosinophilia plays a key role in the pathogenesis of asthma and nasal polyps in patients with aspirin hypersensitivity. OBJECTIVE: To evaluate the expression of vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule I (ICAM-1) and their ligands (the integrins lymphocyte function-associated antigen 1 and very late-activation antigen 4 [VLA-4]) in nasal polyps of patients with aspirin hypersensitivity compared with aspirin-tolerant individuals. METHODS: Immunohistochemical studies were performed using a peroxidase method and monoclonal antibodies on 6-microm-thick cryostat sections cut from frozen polyps collected during elective surgery from 21 aspirin-sensitive and 23 aspirin-tolerant patients. RESULTS: The mean +/- SD values of the semiquantitatively evaluated immunoexpression of ICAM-1, VCAM-1, and VLA-4 were significantly increased in patients with aspirin hypersensitivity compared with aspirin-tolerant patients (1.7 +/- 0.8 vs 0.9 +/- 0.8, P < .003; 1.8 +/- 0.8 vs 0.8 +/- 0.8, P < .001; and 2.2 +/- 0.7 vs 1.3 +/- 0.7, P < .001, respectively), whereas the mean +/- SD values of the expression of lymphocyte function-associated antigen 1 did not differ significantly (2.4 +/- 0.5 vs 2.2 +/- 0.9; P = .57). We found a correlation between the immunoexpression of VCAM-1 and its ligand VLA-4 in all studied tissue samples (r = 0.4; P < .02). CONCLUSIONS: In nasal polyps of aspirin-hypersensitive patients, up-regulation of the adhesion molecules ICAM-1 and VCAM-1 and the integrin VLA-4 may play an important role in the development of chronic eosinophilic inflammation.     

Nerve growth factor (NGF) promotes angiogenesis in the quail chorioallantoic membrane.

Angiogenesis, the formation of new blood vessels, is tightly regulated by growth factors, such as vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF). The authors hypothesize that nerve growth factor (NGF), a well known neurotrophin, may play a direct angiogenic role. To test this hypothesis, the authors measured the effects of NGF on the natural vascularization of the quail chorioallantoic membrane (CAM). The angiogenic effect of NGF was compared to that of human recombinant VEGF165 (rhVEGF) and basic FGF (rhbFGF). In comparison to phosphate-buffered saline-treated controls, NGFs from different biological sources (mouse, viper, and cobra) increased the rate of angiogenesis in a dose-dependent fashion from 0.5 to 5 microg. For quantitative morphometry, grayscale images of the blood vessels end points of the CAM arteries were binarized for visualization and skeletonized for quantization by fractal analysis. In mouse NGF-treated embryos the fractal dimension (Df), indicative of arterial vessel length and density, increased to 1.266 +/- 0.021 compared to 1.131 +/- 0.018 (p < .001) for control embryos. This effect was similar to that of 0.5 microg rhVEGF (1.290 +/- 0.021, p < .001) and 1.5 microg rhbFGF (1.264 +/- 0.028, p < .001). The mouse NGF-induced angiogenic effect was blocked by 1 microM K252a (1.149 +/- 0.018, p < .001), an antagonist of the NGF/trkA receptor, but not by 1 microM SU-5416 (1.263 +/- 0.029, p < .001), the VEGF/Flk1 receptor antagonist, indicating a direct, selective angiogenic effect of NGF via quail embryo trkA receptor activation. These results confirm previous observations that NGF has angiogenic activity and suggest that this neurotrophin may also play an important role in the cardiovascular system, besides its well-known effects in the nervous system. The angiogenic properties of NGF may be beneficial in engineering new blood vessels and for developing novel antiangiogenesis therapies for cancer.     

Reduction of soluble adhesion molecules (sICAM-1, sVCAM-1, and sE-selectin) and vascular endothelial growth factor levels in serum of rheumatoid arthritis patients following multiple intravenous infusions of infliximab

INTRODUCTION: The purpose of this study was to determine the effect of repeated infusions of infliximab, a chimeric anti-tumor necrosis factor (anti-TNF)-alpha antibody, on the levels of soluble adhesion molecules and vascular endothelial growth factor (VEGF) in patients with active rheumatoid arthritis (RA). MATERIALS AND METHODS: The treatment design consisted of 9 infusions of infliximab (3 mg/kg) at weeks 0, 2, 6, and every 8 weeks thereafter. All patients had been receiving methotrexate (MTX; 7.5-20 mg/week). Serum levels of soluble intercellular adhesion molecule (sICAM)-1, vascular cell adhesion molecule (sVCAM)-1, E-selectin (sE-selectin), and VEGF were measured by ELISA at weeks 0, 2, 6, 14, and 38 prior to infusion, and at week 62. RESULTS: A remarkable decrease in serum sICAM-1 (p<0.001), sVCAM-1 (p<0.01), sE-selectin (p<0.01) and VEGF (p<0.001) levels was observed in RA patients after the initial dose of infliximab. The second administration of the drug was followed by an even more significant suppression of serum sICAM-1, sVCAM-1, sE-selectin, and VEGF (p<0.001 in all cases). Further infliximab infusions also significantly reduced serum soluble adhesion molecules and VEGF concentrations, although these were less effective. Infliximab treatment induced a significant decrease in the number of monocytes observed until the end of the study. CONCLUSIONS: Our study, besides a rapid suppression of disease activity, showed that serum soluble adhesion molecules and VEGF concentrations are down-regulated following anti-TNF-alpha antibody therapy combined with MTX. Repeated doses of infliximab sustained the reductions in the soluble adhesion molecules and VEGF concentrations, although they were less effective than the first and second infusions of infliximab.     

Proanthocyanidins and Flavan-3-ols in the Prevention and Treatment of Periodontitis—Immunomodulatory Effects,Animal and Clinical Studies

This paper continues the systematic review on proanthocyanidins and flavan-3-ols in the prevention and treatment of periodontal disease and covers the immunomodulatory effects, and animal- and clinical studies, while the other part discussed the direct antibacterial properties. Inflammation as a major response of the periodontal tissues attacked by pathogenic microbes can significantly exacerbate the condition. However, the bidirectional activity of phytochemicals that simultaneously inhibit bacterial proliferation and proinflammatory signaling can provide a substantial alleviation of both cause and symptoms. The modulatory effects on various aspects of inflammatory and overall immune response are covered, including confirmed and postulated mechanisms of action, structure activity relationships and molecular targets. Further, the clinical relevance of flavan-3-ols and available outcomes from clinical studies is analyzed and discussed. Among the numerous natural sources of flavan-3-ols and proanthocyanidins the most promising are, similarly to antibacterial properties, constituents of various foods, such as fruits of Vaccinium species, tea leaves, grape seeds, and tannin-rich medicinal herbs. Despite a vast amount of in vitro and cell-based evidence of immunomodulatory there are still only a few animal and clinical studies. Most of the reports, regardless of the used model, indicated the efficiency of these phytochemicals from cranberries and other Vaccinium species and tea extracts (green or black). Other sources such as grape seeds and traditional medicinal plants, were seldom. In conclusion, the potential of flavan-3-ols and their derivatives in prevention and alleviation of periodontal disease is remarkable but clinical evidence is urgently needed for issuing credible dietary recommendation and complementary treatments.     

How Do Dieticians on Instagram Teach? The Potential of the Kirkpatrick Model in the Evaluation of the Effectiveness of Nutritional Education in Social Media

The growing popularity of health education on social media indicates the need for its appropriate evaluation. This paper aims to present the potential of the Kirkpatrick Model (KM) with New World Kirkpatrick Model (NWKM) additions to evaluate the nutritional education provided by dieticians via Instagram. Instagram profiles of ten dieticians providing nutritional education for their followers were analyzed in March and April 2021. The study sample included profiles of both macro- and micro-influencers. The analyzed quantitative data included Instagram Engagement Rate and the number of likes and comments per post. The qualitative analysis of the comments was performed following the theoretical framework provided by the KM and NWKM. Collected data showed followers’ satisfaction, commitment, and relevance of the presented content, fulfilling the Level 1 of NWKM. Level 2 of NWKM was represented by 4 out of 5 dimensions (knowledge, attitude, confidence, commitment). No comments were found only for skills. Both Levels 3 (Behavior) and 4 (Results) of the KM were met. However, the use of the NWKM for them seems limited. The KM can be used to evaluate nutritional education on social media. The NWKM additions seem applicable mostly for Levels 1 and 2.     

Effect of nociceptin on alcohol intake in alcohol-preferring rats

The present study investigated the effect of nociceptin (NC), the endogenous ligand of the opioid-like orphan receptor ORL1, on ethanol intake in genetically selected Marchigian Sardinian alcohol-preferring (msP) rats. Acute intracerebroventricular (ICV) injection of 250 or 500 ng/rat of NC, just before access to 10% ethanol (offered 2 h/day), significantly increased ethanol intake. Subchronic (7 days) ICV injection of 500 ng/rat of NC, given just before access to 10% ethanol (for 30 min/day), resulted in a progressive decrease in ethanol consumption. After the end of NC treatment, rats progressively recovered their usual ethanol intake. When NC, 500 or 1000 ng/rat, was tested versus the effect of ethanol in the place conditioning paradigm, NC significantly reduced the increase in time spent in the ethanol-paired compartment after conditioning. This finding suggests that NC reduces the rewarding properties of ethanol in msP rats; thus, they may respond to the acute NC administration by increasing their ethanol intake in an attempt to achieve the usual reinforcing effect of ethanol, whereas subchronic NC treatment may result in extinction of ethanol drinking. The results of the present study suggest that the brain NC mechanisms may represent an interesting target of pharmacological interventions for the treatment of alcoholism. Received: 11 August 1998/Final version: 15 October 1998     

Chronopharmacokinetics of amitriptyline in rats

The circadian changes in absorption, tissue distribution and elimination of amitriptyline after single intravenous (i.v.) and intragastric (i.g.) administration, as well as the differences in pharmacokinetic profile after multiple i.g. administration (at 10:00 and 22:00 h) during a 12 h dosing interval, were investigated. The circadian changes of pharmacokinetic parameters of amitriptyline such as AUC (serum and tissues), clearance (i.v. and i.g.), volume of distribution, biological half-life and bioavailability were estimated. Acrophases for clearance appeared between 19:00 and 21:00 h; the bioavailability was highest during the dark phase at around 04:00 h. Higher values of AUC in serum were observed at the beginning of the light phase. A circadian rhythm of tissue distribution (AUC, K(D)) of amitriptyline with acrophase in the dark phase was observed for brain (12 h period), lung and liver (24 h), but not for heart or kidney. After single (i.v. and i.g.) amitriptyline administration, concentrations of its major metabolite, nortriptyline, were negligible; however, after ten doses, nortriptyline serum and tissue levels were similar to the concentrations of the parent drug with higher values during the day (light phase).     

Development of a CT Image Analysis Model for Cast Iron Products Based on Artificial Intelligence Methods

This paper presents an assessment of the possibility of using digital image classifiers for tomographic images concerning ductile iron castings. The results of this work can help the development of an efficient system suggestion allowing for decision making regarding the qualitative assessment of the casting process parameters. Special attention should be focused on the fact that automatic classification in the case of ductile iron castings is difficult to perform. The biggest problem in this aspect is the high similarity of the void image, which may be a sign of a defect, and the nodular graphite image. Depending on the parameters, the tests on different photos may look similar. Presented in this article are test scenarios of the module analyzing two-dimensional tomographic images focused on the comprehensive assessment by convolutional neural network models, which are designed to classify the provided image. For the purposes of the tests, three such models were created, different from each other in terms of architecture and the number of hyperparameters and trainable parameters. The described study is a part of the decision-making system, supporting the process of qualitative analysis of the obtained cast iron castings.     

Valorisation of Recycled Cement Paste: Feasibility of a Short-Duration Carbonation Process

Cement paste powder (CPP) is a by-product of the recycling process of concrete with an elevated carbonation capability and potential to be recycled as a binding material in new concrete batches. The application of a carbonation treatment to CPP improves this potential even more, besides the evident gains in terms of CO₂ net balance. However, the long duration usually adopted in this treatment, from 3 to 28 days, hampers the industrial viability of the process. We studied the feasibility of a short-duration carbonation process, with a duration of two hours, carrying out a comprehensive characterization of the material throughout the process. The test was performed on CPP with an average initial water content of 16.9%, exposed to a CO₂ concentration of 80%. The results demonstrate two main carbonation rates: a rapid growth rate in the first 18 minutes of the process, involving all the calcium-bearing compounds in CPP, and a slow growth rate afterwards, where only C-S-H contributes to the carbonation reaction. During the 2 h carbonation process, the main CPP compounds, calcium silicate hydrate (C-S-H) and calcium hydroxide (CH), reached different carbonation degrees, 31% and 94%, with, however, close CO₂ uptake values, 8% and 11%, respectively. Nevertheless, the total CO₂ uptake for this process (≈19%) attained values not distant from the values usually obtained in a carbonation of 12 days or more (19–25%). Hence, these findings highlight the blocking role of C-S-H in the carbonation process, indicating that longer carbonation periods are only going to be useful if an effective carbonation of this compound is accomplished. In the present scenario, where CH is the main contributor to the reaction, the reduction in the process duration is feasible.