Our observations indicated that short-term nonsurgical therapy resulted in a significant improvement in periodontal indices and in a marked decrease of IL-1β, IL-8 and MMP-8 gingival crevicular fluid levels. Nevertheless, no significant correlations were found between clinical parameters and amounts of humoral factors after therapy.

It is well known that mast cell number increases in local tissues under different pathophysiologic conditions, although the humoral factors that stimulate local mast cell accumulation within tissues are not yet well known. Taking into account that tumor necrosis factor (TNF) influences tissue mast cell activity in various ways, the aim of the present study was to investigate the chemotactic activity of TNF for rat peritoneal mast cells. We have found that TNF induces mast cell migratory response in a dose-dependent manner, even in the absence of extracellular matrix (ECM) proteins. Significant migration was observed at concentrations of TNF as low as approximately 3 fM; higher TNF concentrations caused significant inhibition of spontaneous mast cell migration. In the presence of ECM proteins, TNF induced migration of mast cells in a biphasic manner, with peaks of migration occurring at approximately 0.3 fM and approximately 60 pM (in the presence of fibronectin) and at approximately 0.6 fM and approximately 600 pM (in the presence of laminin). Under the same experimental conditions, RANTES induced dose-dependent mast cell migration, and the optimal concentration of this chemokine for maximal migration was approximately 13 nM. The mast cell migratory response to lower concentrations of TNF was chemotactic and to higher TNF concentrations was due to chemokinesis. TNF-induced mast cell migration was completely blocked by neutralizing anti-TNF and anti-TNFR1 antibodies. The tyrosine kinase inhibitor, genistein, significantly abrogated mast cell migration toward TNF. Additionally, we have documented that TNF does not induce degranulation of rat mast cells. Taken together, our results indicate that TNF serves as an extremely potent chemotactic factor for rat mast cells that would cause accumulation of these cells at the site of diverse pathophysiologic conditions accompanied by inflammation.

The aim of our study was to determine whether some bacterial components as well as some proinflammatory cytokines can affect surface mast cell levels. By the use of flow cytometry technique, we documented that freshly isolated mature rat peritoneal mast cells do express surface TLR2 and TLR4 protein, but not CD14 molecules, and respond to stimulation with TLR2 and TLR4 ligands by cysteinyl leukotriene generation. The level of TLR2 protein is modulated by PGN and CCL5 treatment, but not by LPS, LAM, TNF, or IL-6. Surface mast cell TLR4 expression is affected by LPS, LAM, IL-6, and CCL5. Considering that TLR-mediated activation conditions not only engaged these cells in antibacterial defense and development of inflammation but also might influence allergic processes, our observations that surface TLR2 and TLR4 expression can be regulated both bacterial components and proinflammatory cytokines seem to be very intriguing and importance.

IntroductionChronic urticaria (CU) belongs to a group of psychodermatological disorders, thus stress can play a significant role in this dermatosis onset and/or exacerbation. On the other hand, the disease itself accompanied by itch, may be a source of distress and could worsen patients’ quality of life (QoL).AimThe first goal of our study was to compare stress intensity between CU subjects and the control group. The second aim was to investigate the relationships between disease-related parameters (CU severity, itch) and psychological variables (stress and QoL) in CU patients.Material and methodsForty-six female patients with CU participated in our study. Thirty-three healthy females constituted a control group. The following methods were applied: Urticaria Activity Score (UAS), Itch Severity Evaluation Questionnaire, Visual analogue scale (VAS), Social Readjustment Rating Scale (SRRS) and the Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL).ResultsChronic urticaria patients demonstrated a significantly higher stress level in comparison to the control group (z = 2.699; p < 0.001). Regarding the total pruritus score, all CU-Q2oL dimensions were affected, except for subscale swelling/mental status. The strongest link was revealed between global itch and QoL subscale embarrassment (r = 0.51, p < 0.001). There were also statistically significant correlations between stress (VAS scale and SRRS) and QoL (all at least p < 0.05).Conclusions: Taking into account the significant pruritus contribution to QoL impairment, it would be worth employing itch-coping trainings in the CU group. As a consequence, feeling of self-control and self-efficacy could be enhanced, thus resulting in the well-being improvement.

Cathelicidins represent a family of cationic peptides involved in host defense systems. Apart from exerting direct anti-microbial effects, cathelicidins can regulate immune responses by affecting the activity of cells playing a role in antibacterial defense. Taking into account that mast cells are critical components of host defense, the aim of this study was to determine whether rat cathelicidin-related anti-microbial peptide (rCRAMP) can influence mast cell activity. We have demonstrated that activation of fully mature rat mast cells with rCRAMP resulted in generation and release of cysteinyl leukotrienes (cysLTs). However, rCRAMP failed to induce mast cell degranulation and histamine release. We also found that rCRAMP stimulated rat mast cells to synthesize TNF, but not CXCL8. What is more, this peptide induced GM-CSF, IL-1β, CCL2 and CCL3 but not IL-33 mRNA expression in mast cells. Finally, we showed that this cathelicidin serves as potent chemoattractant for rat mast cells. rCRAMP-mediated cysLT synthesis and mast cell migration were strongly inhibited by IL-10 pre-treatment. With the use of specific inhibitors, we established that activation of PLC/A2 and ERK1/2, but not p38, was required for rCRAMP-induced mast cell stimulation, while PI3K-dependent pathway is involved in both TNF synthesis and mast cell migration. Our results suggest that cathelicidins can amplify inflammatory responses by causing mast cells accumulation and by stimulating these cells to release potent pro-inflammatory mediators.

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Cognitive impairment is a significant clinical problem both in multiple sclerosis (MS) and systemic lupus erythematosus (SLE) patients. In MS cognitive dysfunction has been associated with brain atrophy and total demyelinating lesion volume. In SLE cognitive impairment is much less understood, and its link to structural brain damage remains to be established. The aim of this study was to identify the relationship between subcortical gray matter volume and cognitive impairment in MS and SLE. We recruited 37 MS and 38 SLE patients matched by age, disease duration and educational level. Patients underwent magnetic resonance imaging (MRI) and a battery of psychometric tests. Severity of cognitive impairment was similar in both cohorts despite larger white matter lesion load in MS patients. Psychometric scores were associated with global and subcortical gray matter atrophy measures and lesion load in MS, but not in SLE. In SLE, the lack of a relationship between cognitive impairment and structural damage, defined either as atrophy or white matter lesions, indicates a different causal mechanism of cognitive deficit.

Introduction: Kufor-Rakeb syndrome (KRS) is a rare autosomal recessive neurodegenerative disorder manifesting as juvenile-onset atypical parkinsonism with pyramidal signs, supranuclear gaze palsy, dementia and characteristic minimyoclonus, with a notable phenotype variability. The responsible gene ATP13A2 was also associated with hereditary spastic paraplegia, uncomplicated early-or late-onset parkinsonism and a form of neuronal ceroid lipofuscinosis. We present clinical and ultrastructural findings in a 28-year-old woman with novel biallelic ATP13A2 mutations. Material and methods: An ultrastructural study of the skin and muscle sample was carried out. Sequence analysis of all protein coding exons and exon-intron boundaries of genes was performed on patient's genomic DNA. A proprietary oligonucleotide-selective sequencing method was used for capturing genomic targets and sequencing was performed using Illumina sequencing system. Results: The patient presented with juvenile-onset progressive parkinsonian syndrome and cognitive deterioration, accompanied by mild spastic paraplegia, supranuclear gaze palsy, cerebellar syndrome, peripheral neuropathy and fine myoclonus. Plentiful and varied osmiophilic deposits were found in skin and muscle biopsy. Sequence analysis identified two novel heterozygous variants in ATP13A2: a nonsense variant c.2209C>T, p.(Gln737*) and a 2-bp deletion c.2366_2367delTC, p.(Leu789Argfs*15) causing a frameshift leading to a premature stop codon. Oral levodopa treatment was initiated resulting in marked improvement of bradykinesia, rigidity, speech and swallowing. Conclusions: We report two novel ATP13A2 pathogenic mutations, further expanding the phenotype of Kufor-Rakeb syndrome with the unusual features of ataxia and polyneuropathy. We thoroughly describe ultrastructural findings and document a meaningful response to levodopa.