Objectives: Peptidylarginine deiminases (PADs) are a family of calcium-dependent enzymes catalysing the conversion of arginine residues to citrulline, which may constitute a risk factor in rheumatoid ...arthritis (RA) pathogenesis. We investigated PAD activation by serum (PAD
Act
) in early RA, and the associations between PAD activation and disease characteristics, treatment response, and progression of radiographic damage.
Method: Sera from disease-modifying anti-rheumatic drug (DMARD)-naïve early RA patients (n = 225), classified according to the 2010 American College of Rheumatology/European League Against Rheumatism criteria, and healthy controls (n = 63) were analysed for PAD4 activating capacity at 0, 3, 12, and 24 months using a high-performance liquid chromatography fluorometric method. Associations for PAD
Act
were evaluated by Mann-Whitney U and chi-squared tests. Changes in PAD
Act
levels were compared using the Wilcoxon signed-rank test.
Results: PAD
Act
positivity occurred in 42% (n = 95) of the patients and was more prevalent in anti-citrullinated protein antibody (ACPA)-positive vs ACPA-negative patients (47% vs 20%, p = 0.002), but not in rheumatoid factor (RF)-positive vs RF-negative patients (44% vs 38%, p = 0.49). PAD
Act
-positive were younger than PAD
Act
-negative patients mean ± sd 48.7 ± 13.5 vs 53.2 ± 13.7 years, p = 0.011. Median 25th, 75th percentile PAD
Act
levels were higher in patients than in controls (8768 7491, 11 393 vs 7046 6347, 7906, p < 0.0001) and decreased after initiation of DMARD treatment, but were not associated with treatment response or progression of radiographic damage after 2 years of follow-up.
Conclusion: Serum capacity to activate PAD4 was associated with ACPA and RF positivity and earlier disease onset in early RA patients, and decreased after initiation of DMARD treatment, indicating that anti-PAD treatment could potentially be beneficial in RA.
Background and Objective
Nutrition and body weight are modifying factors for periodontitis. The purpose of this study was to quantify two molecules (ghrelin and chemerin), released in association ...with food intake and obesity, in periodontally healthy and diseased individuals with respect to different body mass categories.
Material and Methods
The two main groups (patients with chronic periodontitis and periodontally healthy/gingivitis volunteers) were subdivided into groups of subjects with normal weight body mass index (BMI) <25 and groups of overweight/obese subjects (BMI ≥25). Subgingival bacteria were analysed and the levels of acylated and total ghrelin, chemerin and interleukin‐1β (IL‐1β) were assessed in saliva, gingival crevicular fluid and serum.
Results
The amount of Treponema denticola present subgingivally was significantly higher in the groups of patients with chronic periodontitis as well as in periodontally healthy/gingivitis individuals with BMI ≥25 than in periodontally healthy/gingivitis individuals with BMI <25. The amount of total ghrelin in gingival crevicular fluid differed significantly between the groups, with the lowest levels found in the group of patients with chronic periodontitis and BMI ≥25. The levels of chemerin in gingival crevicular fluid were significantly higher in each chronic periodontitis group than in periodontally healthy/gingivitis individuals with BMI <25. However, the level of IL‐1β in the gingival crevicular fluid was most differentiating between the groups, with the highest levels found in the group of patients with chronic periodontitis and BMI <25 and the lowest levels in periodontally healthy/gingivitis individuals with BMI <25. No significant differences between any groups were seen for chemerin or for acylated ghrelin in the stimulated whole saliva, or for acylated and total ghrelin in peripheral blood serum. The BMI correlated with the serum level of chemerin.
Conclusion
Low ghrelin and high chemerin levels in the gingival crevicular fluid might be linked to periodontal disease and overweight/obesity. However, unlike IL‐1β, the levels of chemerin and ghrelin in gingival crevicular fluid are not reliable indicators of periodontal destruction.
Summary
In periodontitis, an effective host‐response is primarily related to neutrophils loaded with serine proteases, including elastase (NE) and protease 3 (PR3), the extracellular activity of ...which is tightly controlled by endogenous inhibitors. In vitro these inhibitors are degraded by gingipains, cysteine proteases produced by Porphyromonas gingivalis. The purpose of this study was to determine the level of selected protease inhibitors in gingival crevicular fluid (GCF) in relation to periodontal infection. The GCF collected from 31 subjects (nine healthy controls, seven with gingivitis, five with aggressive periodontitis and 10 with chronic periodontitis) was analyzed for the levels of elafin and secretory leukocyte protease inhibitor (SLPI), two main tissue‐derived inhibitors of neutrophil serine proteases. In parallel, activity of NE, PR3 and arginine‐specific gingipains (Rgps) in GCF was measured. Finally loads of P. gingivalis, Aggregatibacter actinomycetemcomitans, Tannerella forsythia and Treponema denticola were determined. The highest values of elafin were found in aggressive periodontitis and the lowest in controls. The quantity of elafin correlated positively with the load of P. gingivalis, Ta. forsythia and Tr. denticola, as well as with Rgps activity. In addition, NE activity was positively associated with the counts of those bacterial species, but not with the amount of elafin. In contrast, the highest concentrations of SLPI were found in periodontally healthy subjects whereas amounts of this inhibitor were significantly decreased in patients infected with P. gingivalis. Periodontopathogenic bacteria stimulate the release of NE and PR3, which activities escape the control through degradation of locally produced inhibitors (SLPI and elafin) by host‐derived and bacteria‐derived proteases.
Summary
We have previously shown that benzamidine‐type compounds can inhibit the activity of arginine‐specific cysteine proteinases (gingipains HRgpA and RgpB); well‐known virulence factors of ...Porphyromonas gingivalis. They also hinder in vitro growth of this important periodontopathogenic bacterium. Apparently growth arrest is not associated with their ability to inhibit these proteases, because pentamidine, which is a 20‐fold less efficient inhibitor of gingipain than 2,6‐bis‐(4‐amidinobenzyl)‐cyclohexanone (ACH), blocked P. gingivalis growth far more effectively. To identify targets for benzamidine‐derived compounds other than Arg‐gingipains, and to explain their bacteriostatic effects, P. gingivalis ATCC 33277 and P. gingivalis M5‐1‐2 (clinical isolate) cell extracts were subjected to affinity chromatography using a benzamidine–Sepharose column to identify proteins interacting with benzamidine. In addition to HRgpA and RgpB the analysis revealed heat‐shock protein GroEL as another ligand for benzamidine. To better understand the effect of benzamidine‐derived compounds on P. gingivalis, bacteria were exposed to benzamidine, pentamidine, ACH and heat, and the expression of gingipains and GroEL was determined. Exposure to heat and benzamidine‐derived compounds caused significant increases in GroEL, at both the mRNA and protein levels. Interestingly, despite the fact that gingipains were shown to be the main virulence factors in a fertilized egg model of infection, mortality rates were strongly reduced, not only by ACH, but also by pentamidine, a relatively weak gingipain inhibitor. This effect may depend not only on gingipain inhibition but also on interaction of benzamidine derivatives with GroEL. Therefore these compounds may find use in supportive periodontitis treatment.
Proteases are of significant importance for the virulence of
Staphylococcus aureus. Nevertheless, their subset, the serine protease-like proteins, remains poorly characterized. Here presented is an ...investigation of SplB protease catalytic activity revealing that the enzyme possesses exquisite specificity and only cleaves efficiently after the sequence Trp-Glu-Leu-Gln. To understand the molecular basis for such selectivity, we solved the three-dimensional structure of SplB to 1.8 Å. Modeling of substrate binding to the protease demonstrated that selectivity relies in part on a canonical specificity pockets-based mechanism. Significantly, the conformation of residues that ordinarily form the oxyanion hole, an essential structural element of the catalytic machinery of serine proteases, is not canonical in the SplB structure. We postulate that within SplB, the oxyanion hole is only formed upon docking of a substrate containing the consensus sequence motif. It is suggested that this unusual activation mechanism is used in parallel with classical determinants to further limit enzyme specificity. Finally, to guide future development, we attempt to point at likely physiological substrates and thus the role of SplB in staphylococcal physiology.
The major Christian denominations over the centuries have developed structures of authority and decision-making. It is intended to prove, that in the Roman Catholic Church, the focus has shifted ...toward primacy, while the Orthodox Churches are considered to be governed in the most synodal manner. The existing models of authority have their advantages and disadvantages, influencing decision-making and shaping synodal structures. In the article, using the methods of analysis, interpretation and comparison, the structures of authority and decision-making in the Orthodox Churches and the Roman Catholic Church will be displayed, and on this basis, their strengths and weaknesses will be detected. The following questions will be answered in turn: how do primatial structures function in the churches? What is the shared responsibility for decision-making in synodal structures? What are the strong and weak points in the churches’ primatial and synodal structures? Based on the answers to these proposals, de-clericalisation of the primatial appointments and preventing synodal bodies from substantive failures will be formulated.
The article discusses the theological criticism of capitalism on the part of the Reformed Churches. The four main themes of criticism are: 1) immoderate accumulation of goods and capital and the ...commodification of man; 2) leading Third World countries to unpayable debt; 3) plundering of natural goods and environmental damage; 4) the trap of unrestrained growth. The idea of “degrowth” is proposed as an effective way out of these threats. This idea consists of moderation in the production of goods adapted in volume to real needs, respect for the environment by implementing the principles of sustainable development, and finally adopting the attitude of self-restraint as a necessary form of asceticism. “Degrowth” is therefore an idea that also brings together the ways to overcome the “economy of greed” and introduce the “economy of life.”
Współczesne rozumienie zjawiska przedsiębiorczości, znacznie odbiegające od klasycznego ekonomicznego ujęcia, sprawia, że coraz częściej łączymy je z edukacją rozumianą jako proces samodoskonalenia ...trwający całe życie. Jednym ze sposobów kształtowania cech przedsiębiorczości jest uczenie się zarządzania czasem. Ta umiejętność w znacznym stopniu decyduje o zaradności życiowej i pozwala osiągać sukcesy. Celem niniejszego artykułu jest przedstawienie sposobu organizacji różnorodnych aktywności dzieci w okresie edukacji wczesnoszkolnej w opinii rodziców i związanych z tym problemów. Badania zostały zrealizowane przy pomocy metody sondażu diagnostycznego z wykorzystaniem techniki ankiety online oraz wywiadów w formie rozmowy. Kształtowanie postaw życiowych dziecka w wieku wczesnoszkolnym jest nierozerwalnie związane z umiejętnością organizacji i planowania czasu. Stopień opanowania technik zarządzania czasem zarówno przez rodziców, jak i dzieci, jest zróżnicowany, co uwidoczniają badania. Postuluje się dalsze rozwijanie umiejętności w tym zakresie.
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