Age-Associated B Cell Features of the Murine High-Grade B Cell Lymphoma Bc.DLFL1 and Its Extranodal Expansion in Abdominal Adipose Tissues.

Diffuse large B cell lymphoma comprises a heterogeneous group of B cell-derived tumors, with different degrees of aggressiveness, as defined by their cellular origin and tissue microenvironment. Using the spontaneous Bc.DLFL1 lymphoma originating from a BALB/c mouse as a diffuse large B cell lymphoma model, in this study we demonstrate that the lymphoma cells display surface phenotype, IgH V-region somatic mutations, transcription factor characteristics and in vivo location to splenic extrafollicular regions of age-associated B cells (ABCs), corresponding to T-bet+ and Blimp-1+/CD138- plasmablasts derivation. The expansion of lymphoma cells within lymphoid tissues took place in a close arrangement with CD11c+ dendritic cells, whereas the extranodal infiltration occurred selectively in the mesentery and omentum containing resident gp38/podoplanin+ fibroblastic reticular cells. Antagonizing BAFF-R activity by mBR3-Fc soluble receptor fusion protein led to a significant delay of disease progression. The extranodal expansion of Bc.DLFL1 lymphoma within the omental and mesenteric adipose tissues was coupled with a significant change of the tissue cytokine landscape, including both shared alterations and tissue-specific variations. Our findings indicate that while Bc.DLFL1 cells of ABC origin retain the positioning pattern within lymphoid tissues of their physiological counterpart, they also expand in non-lymphoid tissues in a BAFF-dependent manner, where they may alter the adipose tissue microenvironment to support their extranodal growth.

Incidence, features, and outcome of disease relapse after COVID-19 vaccination in patients with idiopathic inflammatory myopathies.

INTRODUCTION/AIMS: Vaccination against coronavirus disease 2019 (COVID-19) is relatively safe in patients with idiopathic inflammatory myopathies (IIM); however, myositis flares following vaccination have been poorly studied. We aimed to evaluate the frequency, features, and outcomes of disease relapses in patients with IIM following COVID-19 vaccination. METHODS: A cohort of 176 IIM patients were interviewed after the third wave of the COVID-19 pandemic and followed prospectively. Relapses were determined using the disease state criteria and the outcome of the flares with myositis response criteria, calculating the total improvement score (TIS). RESULTS: A total of 146 (82.9%) patients received a vaccination, 17/146 (11.6%) patients had a relapse within 3 mo, and 13/146 (8.9%) patients within 1 mo. The relapse rate of unvaccinated patients was 3.3%. Three months after the post-vaccination relapses, 70.6% of the patients (12/17) achieved an improvement of disease activity (average TIS score: 30 ± 15.81; seven minor, five moderate, and zero major improvements). Six months after flares improvement was detected in 15/17(88.2%) of relapsed patients (average TIS score: 43.1 ± 19.53; 3 minimal, 8 moderate, and 4 major). Forward stepwise logistic regression analysis revealed that the active state of myositis at the time of injection (p < .0001; odds ratio, 33; confidence interval, 9-120) was significantly associated with the occurrence of a relapse. DISCUSSION: A minority of the vaccinated IIM patients had a confirmed disease flare after COVID-19 vaccination and the majority of the relapses improved after individualized treatment. An active disease state at the time of vaccination probably contributes to the increased risk of a post vaccination myositis flare.

The effect of COVID-19 pandemic on idiopathic inflammatory myositis patients: a single centre experience.

OBJECTIVES: Pandemic caused by coronavirus disease (COVID-19) determines the life of clinicians and patients since 2 years. We have a lot of information about disease course, treatment and protection against virus, but less on the prognosis of infection in patients with idiopathic inflammatory myopathies (IIM). Also few data are available on triggered humoral response and side effects after vaccination. METHODS: Our goal was to assess by a retrospective cross-sectional study the above data in our cohort (176 IIM patients) by identifying COVID-19 positive patients and follow disease course. Incidence and complications of vaccination were determined by questionnaires. 101 patients volunteered for complex blood test. RESULTS: By June 1st, 2021 significantly higher incidence of COVID 19 infections (34.7%) were identified comparing to the national prevalence (8.2%). A third of these infections occurred asymptomatically or mild. Patients requiring hospitalisation had a significantly longer disease duration and a higher incidence of anti-Jo-1 antibody. All patients infected by COVID-19 became seropositive regardless the immunosuppressive therapy or symptoms severity. 54.3% of the patients received anti-COVID-19 vaccine. 72.3% of patients became seropositive after vaccination. Higher antibody titer against spike protein was detected after Pfizer-BioNTech vaccination compared to others. Patients receiving steroid therapy had decreased post-vaccination antibody response compared to those without steroid treatment. No major post-vaccination infection was observed. CONCLUSIONS: Based on our results, myositis may be associated with an increased risk of COVID-19 infection. Independent risk factor for hospitalisation are longer disease duration and anti-Jo1 positivity. Anti-SARS-CoV2 vaccines seem safe and tolerable and strongly recommended for that population.

Bioactive Potential of Elderberry (Sambucus nigra L.): Antioxidant, Antimicrobial Activity, Bioaccessibility and Prebiotic Potential.

Due to its abundance of physiologically active ingredients, one of the oldest medicinal herbs, elderberry (EB) Sambucus nigra L., is beneficial for both therapeutic and dietary purposes. This study determined the bioaccessibility of the phenolic compounds and the prebiotic potential of the polyphenols from freeze-dried EB powder (FDEBP), along with the antioxidant and antimicrobial activities of this extract. The most significant phenolic compounds in black EB are represented by anthocyanins (41.8%), predominating cyanidin-sambubiosides and cyanidin-glucosides (90.1% of the identified anthocyanins). The FRAP assay obtained the highest antioxidant activity value (185 ± 0.18 µmol Fe2+/g DW). The most sensitive to the antimicrobial activity of the extract was proven to be Staphylococcus aureus, and Pseudomonas aeruginosa had the lowest minimum inhibitory concentration of 1.95 mg/mL. To determine the prebiotic potential of the polyphenols, the cell growth of five probiotic strains (Lactobacillus plantarum, L. casei, L. rhamnosus, L. fermentum and Saccharomyces boulardii) was tested. The influence on cell growth was positive for all five probiotic strains used. Overall, the most significant increase (p < 0.05) was recorded at 1.5% FDEBP, on L. casei with a growth index (GI) of 152.44%, very closely followed by GI at 0.5% and 1% concentrations. The stability of the total phenolic compounds through simulated gastronitestinal digestion was increased (93%), and the bioaccessibility was also elevated (75%).

Developed rapid and simple RP-HPLC method for simultaneous separation and quantification of bovine milk protein fractions and their genetic variants.

The aim was to develop a reliable rapid reversed-phase high-performance liquid chromatography (RP-HPLC) method to simultaneously determine the main bovine milk protein fractions, including their genetic variants. Compared to the previous studies, our method is able to separate the main protein fractions within 20 min of total run time. The method validation consisted of testing repeatability, reproducibility linearity, repeatability, and accuracy. The procedure was developed using raw individual, bulk, and commercially available heat-treated cow milk samples. The RSD of peak areas ranged from 1.43 to 3.16% within analytical day and from 3.29 to 6.70% across analytical days. The method can be applied to investigate both raw and heat-treated milk samples.

Evaluation of the Astragalus exscapus L. subsp. transsilvanicus Roots' Chemical Profile, Phenolic Composition and Biological Activities.

Novel and natural molecules for pharmaceutical applications are a contemporary preoccupation in science which prompts research in underexplored environments. Astragalus exscapus ssp. transsilvanicus (Schur) Nyár. (ASTRA) is a plant species endemic to Transylvania, having a very similar root system with that of A. membranaceus (Fisch.) Bunge, known for its health promoting properties. The present study endeavored to perform basic characterization of the ASTRA roots by proximate analysis, to investigate the fatty acid profile of the lipids extracted from the ASTRA roots, to examine the phenolic composition of the root extracts by liquid chromatography, and to evaluate the biological activities through determination of the antioxidant, antimicrobial and cytotoxic capacities of the extracts. The primary compounds found in the ASTRA roots were carbohydrates and lipids, and the fatty acid composition determined by GC-MS showed linoleic acid as preponderant compound with 31.10%, followed by palmitic, oleic and α-linolenic acids with 17.30%, 15.61% and 14.21%, respectively. The methanol extract of the ASTRA roots presented highest phenolic content, Astragaloside IV being the predominant compound with 425.32 ± 0.06 µg/g DW. The antimicrobial assay showed remarkable antimicrobial potential of the extract at a concentration of 0.356 and 0.703 mg ASTRA root powder (DW)/mL, highlighting its efficacy to inhibit S. aureus and S. epidermidis bacterial strains. Furthermore, the cell proliferation assessment showed the noteworthy proficiency of the treatment in inhibiting the proliferation of B16F10 melanoma cells.

Carotenoid Recovery from Tomato Processing By-Products through Green Chemistry.

The recovery of bioactive compounds from agro-industry-derived by-products sustains circular economy principles by encouraging maximized recycling and minimized waste. Tomato processing by-products are abundant in carotenoids, which have several health-promoting properties, and their reintegration into functional food products represents a major interest for scientists and manufacturers. In the present study, carotenoids were recovered from tomato processing by-products based on the principles of green chemistry by using generally recognized as safe (GRAS) solvents, freeze-drying as pretreatment, and ultrasound in the recovery procedure. Spectrophotometric measurements and HPLC were used to identify and quantify total and individual carotenoids from the extracts. The highest values for lycopene (1324.89 µg/g dw) were obtained when ethyl lactate was applied as a solvent, followed by ethyl acetate with slightly smaller differences (1313.54 µg/g dw). The extracts obtained from freeze-dried samples presented significantly lower amounts of lycopene, indicating that carotenoids are highly susceptible to degradation during lyophilization. Flaxseed, grape seed, and hempseed oils were enriched with carotenoids and their rheological measurements showed favorable viscoelastic properties, especially hempseed and flaxseed oil, with viscosity under 50 mPa·s. Considering the results and the economic perspective of carotenoid recovery from tomato processing by-products, ethyl acetate is suitable, sustainable, and environmentally friendly for carotenoid extraction.

Natural Polyphenol Recovery from Apple-, Cereal-, and Tomato-Processing By-Products and Related Health-Promoting Properties.

Polyphenols of plant origin are a broad family of secondary metabolites that range from basic phenolic acids to more complex compounds such as stilbenes, flavonoids, and tannins, all of which have several phenol units in their structure. Considerable health benefits, such as having prebiotic potential and cardio-protective and weight control effects, have been linked to diets based on polyphenol-enriched foods and plant-based products, indicating the potential role of these substances in the prevention or treatment of numerous pathologies. The most representative phenolic compounds in apple pomace are phloridzin, chlorogenic acid, and epicatechin, with major health implications in diabetes, cancer, and cardiovascular and neurocognitive diseases. The cereal byproducts are rich in flavonoids (cyanidin 3-glucoside) and phenolic acids (ferulic acid), all with significant results in reducing the incidence of noncommunicable diseases. Quercetin, naringenin, and rutin are the predominant phenolic molecules in tomato by-products, having important antioxidant and antimicrobial activities. The present understanding of the functionality of polyphenols in health outcomes, specifically, noncommunicable illnesses, is summarized in this review, focusing on the applicability of this evidence in three extensive agrifood industries (apple, cereal, and tomato processing). Moreover, the reintegration of by-products into the food chain via functional food products and personalized nutrition (e.g., 3D food printing) is detailed, supporting a novel direction to be explored within the circular economy concept.

The risk of fracture and prevalence of osteoporosis is elevated in patients with idiopathic inflammatory myopathies: cross-sectional study from a single Hungarian center.

BACKGROUND: The prevalence of osteoporosis and risk of fractures is elevated in rheumatoid arthritis (RA), but we have limited information about the bone mineral density (BMD) and fracture risk in patients with inflammatory myopathies. We intended to ascertain and compare fracture risk, bone mineral density and the prevalence of vertebral fractures in patients with inflammatory myositis and rheumatoid arthritis and to assess the effect of prevalent fractures on the quality of life and functional capacity. METHODS: Fifty-two patients with myositis and 43 patients with rheumatoid arthritis were included in the study. Fracture Risk was determined using FRAX® Calculation Tool developed by the University of Sheffield. Dual energy X-ray absorptiometry and bidirectional thoracolumbar radiographs were performed to assess BMD and vertebral fractures. Quality of life was measured with Short Form-36 (SF-36) and physical function assessment was performed using Health Assessment Questionnaire (HAQ). RESULTS: We found a significantly elevated fracture risk in RA as compared to myositis patients if the risk assessment was performed without the inclusion of the BMD results. If BMD results and glucocorticoid dose adjustment were taken into account, the differences in fracture risk were no longer significant. The prevalence of osteoporosis was found to be significantly higher in the myositis group (7% vs. 13.5%, p: 0.045), but the fracture prevalence was similar in the two groups (75% vs. 68%). The fracture rates were independently associated with age in the myositis group, and with lower BMD results in the RA patients. The number of prevalent fractures was significantly correlated to poorer physical function in both groups, and poorer health status in the myositis group, but not in the RA group. CONCLUSIONS: Our findings suggest that inflammatory myopathies carry significantly elevated risks for osteoporosis and fractures. These higher risks are comparable to ones detected with RA in studies and strongly affect the physical function and quality of life of patients. Therefore further efforts are required to make the fracture risk assessment reliable and to facilitate the use of early preventive treatments.

Adolescents' attitudes towards healthy eating: The role of self-control, motives and self-risk perception.

BACKGROUND: Adolescence is a critical stage in life course development. It is a particularly relevant stage regarding our understanding of eating behaviors since adolescent's evolving, more autonomous food preferences tend to be influenced by peers and media as much if not more than the family. Therefore, exploring adolescent's eating preferences could be an important focus to developing prevention programs. AIMS: To explore the role of psychological variables (namely, self-risk perception, self-control and eating motivations) and their relationships with healthy eating attitudes. METHODS: A sample of adolescents (Szeged, Hungary, N = 274, ages 14-19 years; mean age = 15.95 years, S.D. = 1.17 years; 54% males) was recruited to participate in the study. Data were collected from self-administered/anonymous questionnaires. Besides descriptive statistics, correlations and a path analysis were applied to examine the relationships between self-control, self-risk perception, eating motivations and healthy eating attitudes. RESULTS: Self-control played a decisive role, both directly and indirectly in healthy eating attitudes, while self-risk-perception had a less important mediating role. Eating motives were directly related to eating attitudes but in a different way: health motives were positively associated with healthy eating attitudes, while social and external motives had a negative relationship. CONCLUSIONS: The path analysis suggests that self-control indeed plays an important role in developing healthy attitudes. While health motives play a more decisive role in health-related attitudes than we might expect, self-risk perception plays a limited role perhaps due to the notion that adolescents typically present a feeling of invulnerability. These findings suggest that despite their diminished self-risk perception, adolescents tend to be health conscious in nutrition, particularly when it combines with the underlying impact of self-control and health motives.

Phenolic Compounds from Five Ericaceae Species Leaves and Their Related Bioavailability and Health Benefits.

Some species of the Ericaceae family have been intensively studied because of the beneficial health impact, known since ancient times, of their chemical components. Since most studies focus on the effects of fruit consumption, this review aims to highlight the phenolic components present in the leaves. For this purpose, five species from Ericaceae family (bilberry-Vaccinium myrtillus L., lingonberry-V. vitis-idaea L., bog bilberry-V. uliginosum L., blueberry-V. corymbosum L. and bearberry-Arctostapylos uva-ursi L.) were considered, four of which can be found in spontaneous flora. The chemical composition of the leaves revealed three major phenolic compounds: chlorogenic acid, quercetin and arbutin. The health promoting functions of these compounds, such as antioxidant and anti-inflammatory properties that could have preventive effects for cardiovascular disease, neurodegenerative disorders, cancer, and obesity, have been exemplified by both in vitro and in vivo studies in this review. Furthermore, the importance of bioaccessibility and bioavailability of the phenolic compounds have been summarized. The findings highlight the fact that leaves of some Ericaceae species deserve increased attention and should be studied more profoundly for their biological activities, especially those from spontaneous flora.

Fenugreek (Trigonella Foenum-Graecum) Seed Flour and Diosgenin Preserve Endothelium-Dependent Arterial Relaxation in a Rat Model of Early-Stage Metabolic Syndrome.

Fenugreek is a common herb possessing several bioactive components including diosgenin. Here, dietary fenugreek seed flour and diosgenin were evaluated on a model of endothelium-dependent vasorelaxation by abdominal aortas isolated from rats receiving high-fat, high-sugar diet (HFHSD). 60 male Wistar rats were randomized into six groups: (i) negative control getting conventional rat feed regimen; (ii) positive control receiving HFHSD; (iii) a test group fed 2 g/kg bw/day fenugreek seed flour (containing 10 mg/kg bw/day diosgenin) + HFHSD; (iv) three test groups fed 1, 10 and 50 mg/kg bw/day diosgenin + HFHSD. Alimentary treatments were carried out for six weeks. The abdominal aortas were isolated, and 2 mm wide rings were sectioned off and mounted at a resting tension of 10 mN in organ baths containing Krebs solution (36 °C) exposed to 95% O2 and 5% CO2. After 60-min incubation, a norepinephrine concentration-response (E/c) curve was generated to determine their half-maximal effective concentration (EC50) value. After 60-min wash-out, a pre-contraction with norepinephrine EC50 was made, followed by an acetylcholine E/c curve. Plasma glutathione levels, glutathione-handling enzyme activities and blood antioxidant capacities were also determined. HFHSD significantly decreased the dilatory response to acetylcholine and increased plasma glutathione levels and these effects were significantly reversed by fenugreek seed flour, 10 and 50 mg/kg bw/day diosgenin. Both fenugreek and diosgenin treatments prevent HFHSD-induced endothelial dysfunction and redox changes. As fenugreek treatment was more effective at lower acetylcholine concentrations than diosgenin treatments, components of fenugreek other than diosgenin may contribute to the beneficial effects of dietary fenugreek seed flour.

Insulin-Sensitizer Effects of Fenugreek Seeds in Parallel with Changes in Plasma MCH Levels in Healthy Volunteers.

In developed, developing and low-income countries alike, type 2 diabetes mellitus (T2DM) is one of the most common chronic diseases, the severity of which is substantially a consequence of multiple organ complications that occur due to long-term progression of the disease before diagnosis and treatment. Despite enormous investment into the characterization of the disease, its long-term management remains problematic, with those afflicted enduring significant degradation in quality-of-life. Current research efforts into the etiology and pathogenesis of T2DM, are focused on defining aberrations in cellular physiology that result in development of insulin resistance and strategies for increasing insulin sensitivity, along with downstream effects on T2DM pathogenesis. Ongoing use of plant-derived naturally occurring materials to delay the onset of the disease or alleviate symptoms is viewed by clinicians as particularly desirable due to well-established efficacy and minimal toxicity of such preparations, along with generally lower per-patient costs, in comparison to many modern pharmaceuticals. A particularly attractive candidate in this respect, is fenugreek, a plant that has been used as a flavouring in human diet through recorded history. The present study assessed the insulin-sensitizing effect of fenugreek seeds in a cohort of human volunteers, and tested a hypothesis that melanin-concentrating hormone (MCH) acts as a critical determinant of this effect. A test of the hypothesis was undertaken using a hyperinsulinemic euglycemic glucose clamp approach to assess insulin sensitivity in response to oral administration of a fenugreek seed preparation to healthy subjects. Outcomes of these evaluations demonstrated significant improvement in glucose tolerance, especially in patients with impaired glucose responses. Outcome data further suggested that fenugreek seed intake-mediated improvement in insulin sensitivity correlated with reduction in MCH levels.

FSCPX, a Chemical Widely Used as an Irreversible A1 Adenosine Receptor Antagonist, Modifies the Effect of NBTI, a Nucleoside Transport Inhibitor, by Reducing the Interstitial Adenosine Level in the Guinea Pig Atrium.

Based on in silico results, recently we have assumed that FSCPX, an irreversible A1 adenosine receptor antagonist, inhibits the action of NBTI that is apparent on E/c curves of adenosine receptor agonists. As a mechanism for this unexpected effect, we hypothesized that FSCPX might modify the equilibrative and NBTI-sensitive nucleoside transporter (ENT1) in a way that allows ENT1 to transport adenosine but impedes NBTI to inhibit this transport. This assumption implies that our method developed to estimate receptor reserve for agonists with short half-life such as adenosine, in its original form, overestimates the receptor reserve. In this study, therefore, our goals were to experimentally test our assumption on this effect of FSCPX, to improve our receptor reserve-estimating method and then to compare the original and improved forms of this method. Thus, we improved our method and assessed the receptor reserve for the direct negative inotropic effect of adenosine with both forms of this method in guinea pig atria. We have found that FSCPX inhibits the effects of NBTI that are mediated by increasing the interstitial concentration of adenosine of endogenous (but not exogenous) origin. As a mechanism for this action of FSCPX, inhibition of enzymes participating in the interstitial adenosine production can be hypothesized, while modification of ENT1 can be excluded. Furthermore, we have shown that, in comparison with the improved form, the original version of our method overestimates receptor reserve but only to a small extent. Nevertheless, use of the improved form is recommended in the future.

Bioactive Compounds Extracted from Tomato Processing by-Products as a Source of Valuable Nutrients.

Alongside paper, plastic, metal and glass, an important segment in the recycling area is represented by the wastes of different vegetal processing industries. These by-products gained interest lately, in the context of food waste prevention and growing population number. In the tomato processing industry approximately, 8.5 million tons of wastes are generated globally, each year. The present study highlights the valuable bioactive constituents as lycopene, beta-carotene, glutamic acid or aspartic acid from the by-products of tomato processing industries, which can be revalorized as incorporated nutrients in functional foods. Tomato consumption is directly associated with the prevention of different chronic diseases and carcinogenesis, however the carotenoids bioavailability is a key factor in this process. Further, fiber content together with protein content of tomato seeds and benefits of their consumption are emphasized. Value-added food products obtained by tomato peels or seeds addition are exemplified in this review (bakery, meat products, pasta and noodles, dairy and oil products as well as jams and functional ice cream), in order to embrace next prototypes that can transform vegetal by-products in functional nutrients.

[Study of eating attitudes, behaviour and information-seeking in relation to sociodemographic and psychological factors among adolescents]. / A táplálkozással kapcsolatos attitudök, magatartás és információkeresés vizsgálata és összefüggése szociodemográfiai és pszichológiai változókkal serdülok körében.

INTRODUCTION: Nutrition is one of the key factors in health maintainance. So developing appropriate eating habits is very important in adolescence. Dietary behaviour may be influenced by certain aspects of personality, e.g., self-efficacy, optimism/pessimism and self-control. AIM: We explored adolescents' eating behaviour, attitudes, and information seeking, and their relationship with psychological and sociodemographic factors. METHOD: Participants were high school students (n = 277; 54% boys; mean age: 16 years; SD = 1.25). Our self-administered questionnaire contained items on sociodemographics, eating behaviour and attitudes, and information-seeking as well as three psychological scales. RESULTS: We explored the main factors of behaviour (health-conscious, nonconscious, raw-based), attitudes (rejecting, ambivalent and accepting), and information-seeking (lay, professional, Internet) using factor analysis. Correlation analyses revealed adolescents' nutrition-related behaviour and attitudes were rather health-conscious, but rejecting and ambivalence in their behaviour and attitudes appeared as well. Self-efficacy, self-control and optimism played a role not only in developing health-conscious behaviour and accepting attitude but also in avoiding the nonconscious behaviour and rejecting attitude. Health-conscious behaviour was associated with higher socioeconomic status and parents' schooling but less with gender. Information-seeking was partly influenced by certain sociodemographics: professional resources were preferred by girls, students from grammar schools, and those with better school achievement. CONCLUSIONS: Our data draw attention to the extraordinary importance of mapping adolescent dietary habits; not only their behaviours but also attitudes and information-seeking. This life period is significant in terms of childhood nutrional socialization since youth's decisions become more and more autonomous in this field as well. Orv Hetil. 2018; 159(51): 2183-2192.

Glucopyranosylidene-Spiro-Thiazolinones: Synthetic Studies and Determination of Absolute Configuration by TDDFT-ECD Calculations.

Reactions of O-peracylated C-(1-bromo-ß-d-glucopyranosyl)formamides with thioamides furnished the corresponding glucopyranosylidene-spiro-thiazolin-4-one. While O-debenzoylations under a variety of conditions resulted in decomposition, during O-deacetylations the addition of MeOH to the thiazolinone moiety was observed, and with EtOH and water similar adducts were isolated or detected. The structure and stereochemistry of the new compounds were established by means of NMR and electronic circular dichroism (ECD) data supported by time-dependent density functional theory ECD (TDDFT-ECD) calculations. TDDFT-ECD calculations could efficiently distinguish the proposed epimeric products having different absolute configuration in the spiro heterocyclic ring.

Methodical Challenges and a Possible Resolution in the Assessment of Receptor Reserve for Adenosine, an Agonist with Short Half-Life.

The term receptor reserve, first introduced and used in the traditional receptor theory, is an integrative measure of response-inducing ability of the interaction between an agonist and a receptor system (consisting of a receptor and its downstream signaling). The underlying phenomenon, i.e., stimulation of a submaximal fraction of receptors can apparently elicit the maximal effect (in certain cases), provides an opportunity to assess the receptor reserve. However, determining receptor reserve is challenging for agonists with short half-lives, such as adenosine. Although adenosine metabolism can be inhibited several ways (in order to prevent the rapid elimination of adenosine administered to construct concentration-effect (E/c) curves for the determination), the consequent accumulation of endogenous adenosine biases the results. To address this problem, we previously proposed a method, by means of which this bias can be mathematically corrected (utilizing a traditional receptor theory-independent approach). In the present investigation, we have offered in silico validation of this method by simulating E/c curves with the use of the operational model of agonism and then by evaluating them using our method. We have found that our method is suitable to reliably assess the receptor reserve for adenosine in our recently published experimental setting, suggesting that it may be capable for a qualitative determination of receptor reserve for rapidly eliminating agonists in general. In addition, we have disclosed a possible interference between FSCPX (8-cyclopentyl-N³-[3-(4-(fluorosulfonyl)benzoyloxy)propyl]-N¹-propylxanthine), an irreversible A1 adenosine receptor antagonist, and NBTI (S-(2-hydroxy-5-nitrobenzyl)-6-thioinosine), a nucleoside transport inhibitor, i.e., FSCPX may blunt the effect of NBTI.

Impact of rheumatoid arthritis in oral surgery and implantology treatment based on literature.

Rheumatoid arthritis (RA) is an autoimmune disease that results in a chronic, systemic inflammatory disorder that principally attacks synovial joints. The pathology of the disease process often leads to the destruction of articular cartilage and the bone. Normal bone remodeling cycle requires the balance between bone resorption and bone deposition which is determined by the activities of two principle cell types, namely, osteoclasts and osteoblasts. Osteoblasts and osteoclasts, coupled together via cytokine mediated cell signaling. The dominance of pro-inflammatory cytokines in bone homeostasis leads to osteolysis. Many articles have been published about the pathobiochemical similarity between rheumatoid arthritis and periodontitis, whereas the role of the disease in bone regeneration and osseointegration is less proven. According to the international literature in rheumatoid arthritis, due to frequent periodontitis, decreased salivary secretion, medication, as well as a decrease in bone regenerative potential, rheumatoid arthritis is considered as relative contraindication in implantology. In daily practice, we face more frequently with rheumatoid arthritis which makes the topic so important in oral surgery and implantology. It can be said that adequate preoperative preparation (healthy periodontal status, antibiotic protection, consultation with the rheumatologist to modify medication) interventions can be done more safely. The risk of failure is higher in patients suffering from rheumatoid arthritis of the underlying disease which fact is important to be communicated before surgical intervention.

[The shades of anti-Jo1 positive antisynthetase syndrome in a Hungarian cohort]. / Az anti-Jo-1-pozitív antiszintetáz szindróma jellegzetességei gondozott betegeink alapján.

INTRODUCTION: In idiopathic inflammatory myopathies, the presence of anti-Jo-1 antibody defines a distinct clinical phenotype (myositis, arthritis, interstitial lung disease, Raynaud's phenomenon fever, mechanic's hands), called antisynthetase syndrome. AIM: To determine the demographic data as well as clinical, laboratory and terapeutical features of anti-Jo1 positive patients, followed by the department of the authors. METHOD: The medical records of 49 consecutive anti-Jo1 patients were reviewed. RESULTS: Demographic and clinical results were very similar to those published by other centers. Significant correlation was found between the anti-Jo-1 titer and the creatine kinase and C-reactive protein levels. Distinct laboratory results measured at the time of diagnosis of the disease (C-reactive protein, antigen A associated with Sjogren's syndrome, positive rheumatoid factor), and the presence of certain clinical symptoms (fever, vasculitic skin) may indicate a worse prognosis within the antisyntetase positive patient group. CONCLUSION: In the cases above more agressive immunosuppressive therapy may be required.