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Michael Busse,1 David Stevens,3 Annette Kraegeloh,2 Christian Cavelius,2 Mathias Vukelic,1 Eduard Arzt,2 Daniel J Strauss1,2 1Systems Neuroscience and Neurotechnology Unit, Saarland University, Faculty of Medicine, Neurocenter, and Saarland University of Applied Sciences, Homburg/Saarbruecken, Germany; 2Leibniz Institute for New Materials, Saarbruecken, Germany; 3Department of Physiology, Saarland University, Faculty of Medicine, Homburg/Saarbruecken, Germany Background: Beside the promising application potential of nanotechnologies in engineering, the use of nanomaterials in medicine is growing. New therapies employing innovative nanocarrier systems to increase specificity and efficacy of drug delivery schemes are already in clinical trials. However the influence of the nanoparticles themselves is still unknown in medical applications, especially for complex interactions in neural systems. The aim of this study was to investigate in vitro effects of coated silver nanoparticles (cAgNP) on the excitability of single neuronal cells and to integrate those findings into an in silico model to predict possible effects on neuronal circuits. Methods: We first performed patch clamp measurements to investigate the effects of nanosized silver particles, surrounded by an organic coating, on excitability of single cells. We then determined which parameters were altered by exposure to those nanoparticles using the Hodgkin–Huxley model of the sodium current. As a third step, we integrated those findings into a well-defined neuronal circuit of thalamocortical interactions to predict possible changes in network signaling due to the applied cAgNP, in silico. Results: We observed rapid suppression of sodium currents after exposure to cAgNP in our in vitro recordings. In numerical simulations of sodium currents we identified the parameters likely affected by cAgNP. We then examined the effects of such changes on the activity of networks. In silico network modeling indicated effects of local cAgNP application on firing patterns in all neurons in the circuit. Conclusion: Our sodium current simulation shows that suppression of sodium currents by cAgNP results primarily by a reduction in the amplitude of the current. The network simulation shows that locally cAgNP-induced changes result in changes in network activity in the entire network, indicating that local application of cAgNP may influence the activity throughout the network. Keywords: coated silver nanoparticles, modeling, patch clamp recordings, neuronal circuit model, neuromodulatory effect, nanocarriers, nonviral vectors, Llinás model

This systematic review explores the relationship between achieving minimal disease activity in psoriasis and the progression of atherosclerosis. It investigates how biologic therapies and other treatments impact atherosclerosis markers, offering insights into therapeutic strategies. A comprehensive search of PubMed, Embase, and Web of Science was conducted from January 1, 2000, to April 1, 2023, using terms such as psoriasis, psoriatic arthritis, atherosclerosis, biologic therapy, vascular stiffness, carotid intima-media thickness (CIMT), and coronary computed tomography angiography (CCTA). Eligible studies were those involving human subjects over 18, written in English, that provided quantitative atherosclerosis markers, including CIMT, CCTA, arterial pulse wave velocity (aPWV), fat attenuation index (FAI), and augmentation index (Aix). From an initial pool of 217 studies, 21 were included, grouped by treatments, including TNF-α inhibitors, IL-12/23 inhibitors, IL-17 inhibitors, DMARDs, phototherapy, and fumaric acid esters. The review found that TNF-α inhibitors significantly improved atherosclerosis markers such as CIMT, aPWV, FAI, and C-reactive protein (CRP), with reductions in these markers compared to no treatment, phototherapy, and IL-12/23 inhibitors. Additionally, IL-17 inhibitors demonstrated similar reductions in FAI compared to TNF-α inhibitors but showed a greater effect in reducing non-calcified plaque burden (12% vs. 5% for TNF-α inhibitors, p < 0.001) and also decreased CRP levels. Fumaric acid improved cholesterol metabolism (p < 0.04), and TNF-α inhibitors enhanced endothelial function (p < 0.01). Mixed results were observed when compared to DMARDs, indicating that patient-specific factors should guide treatment choices. In conclusion, TNF-α inhibitors are highly effective in reducing atherosclerosis progression in psoriasis patients, consistently improving vascular health markers like CIMT, aPWV, FAI, and CRP. IL-17 inhibitors also show significant efficacy, particularly in reducing non-calcified plaque burden, making them a valuable alternative to TNF-α inhibitors. Fumaric acid's role in cholesterol metabolism suggests its potential in combination therapies. These findings support integrating TNF-α and IL-17 inhibitors into treatment protocols for psoriasis patients with comorbid atherosclerosis, improving cardiovascular outcomes., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s).)

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by defective regulatory T (T reg ) cells. Here, we demonstrate that a T cell-specific deletion of calcium/calmodulin-dependent protein kinase 4 (CaMK4) improves disease in B6. lpr lupus-prone mice and expands T reg cells. Mechanistically, CaMK4 phosphorylates the glycolysis rate-limiting enzyme 6-phosphofructokinase, platelet type (PFKP) and promotes aerobic glycolysis, while its end product fructose-1,6-biphosphate suppresses oxidative metabolism. In T reg cells, a CRISPR-Cas9-enabled Pfkp deletion recapitulated the metabolism of Camk4 -/- T reg cells and improved their function and stability in vitro and in vivo. In SLE CD4 + T cells, PFKP enzymatic activity correlated with SLE disease activity and pharmacologic inhibition of CaMK4-normalized PFKP activity, leading to enhanced T reg cell function. In conclusion, we provide molecular insights in the defective metabolism and function of T reg cells in SLE and identify PFKP as a target to fine-tune T reg cell metabolism and thereby restore their function.

Background: Periodontal complications are one of the common side effects associated with orthodontic therapy., Objective: This study aimed to evaluate the periodontal changes in patients before, during, and after the therapy with a fixed orthodontic appliance., Methods: Out of 38 healthy adolescents with permanent dentition who were indicated for fixed orthodontic therapy were included in this study. Patients were selected from Class I, treated by non-extraction methods, by using conventional orthodontic braces. After their examination and treatment by an orthodontist, the patients were referred to the periodontist before the placement of a fixed orthodontic appliance. The patients underwent the application of a periodontal anamnestic-diagnostic protocol, and the clinical-radiological evaluation. After a fixed orthodontic appliance was placed, the respondents were referred to the periodontist for regular mandatory check-ups, initially, after three months, and later on-after 6 months, after 1 year and after 2 years until the end of orthodontic therapy., Results: An increase in the mean value of the Plaque Index and Sulcus Bleeding Index was found at each check-up after the placement of a fixed orthodontic appliance. There is a statistically significant difference in the presence of gingival hyperplasia found by monitoring the changes after three and six months, and after one and two years following the start of orthodontic therapy., Conclusion: The assessment of periodontal changes in patients before, during and after the completion of fixed orthodontic therapy revealed that there is a strong need for mutual and close cooperation between orthodontist and periodontist during orthodontic therapy., Competing Interests: None declared., (© 2022 Sanja Hadzic, Mirjana Gojkov-Vukelic, Enes Pasic, Indira Mujic Jahic, Arma Muharemovic, Lejla Redzepagic-Vrazalica, Azra Jeleskovic, Enita Nakas.)

Background: Dentine hypersensitivity (DH) is a frequent clinical problem that represents a long-term painful discomfort for the patients, and for the dentists, it represents a diagnostic and therapeutic challenge., Objective: The aim of the research is to verify the effect of the treatment with diode laser SiroLaser Blue (660nm) of DH alone or in combination with different impregnating agents., Methods: Fifty patients were included in this research, separated into five groups. All the patients have been asked to define the level of dentine hypersensitivity using VAS (0-10). The first group was treated with Fluor Protector, the second group after the application of Fluor Protector has undergone irradiation with SiroLaser Blue (660nm), the third group was treated with impregnating agent Vivasens, the fourth group, after the application of impregnating agent Vivasens, has had SiroLaser Blue (660nm) irradiation. The fifth group has just been treated with SiroLaser Blue (660nm). The efficiency of the treatment was checked using VAS for every group immediately after the conducted treatment, after 7 days and 1 month., Results: Our results showed that all of the desensitizing agents used in the research alone or in combination with a diode laser (660nm) have shown a reduction of DH. The difference has been proven statistically significant in mean values by groups and examinations. Vivasens and diode laser irradiation have provided the best results in the review of mean values after the first examination and one month after the treatment of DH (p<0,05). In our research, the application of diode laser alone has not proven superior to other treatment methods that have been used in the research., Conclusion: Vivasens plus diode laser irradiation has provided the best results even after one month since the treatment of DH., Competing Interests: None declared., (© 2021 Mirjana Gojkov-Vukelic, Sanja Hadzic, Indira Mujic Jahic, Enes Pasic, Arma Muharemovic.)

Aim: Interleukin-23 (IL-23) is a cytokine that promotes the differentiation of T cells into pro-inflammatory Th17. We have previously shown that IL-23 is upregulated in systemic lupus erythematosus (SLE) patients and lupus prone mice. As SLE is highly heterogeneous, we asked whether IL-23 production correlates with different manifestations of the disease. Methods: We recruited 56 subjects who fulfilled the ACR criteria for SLE. Interleukin-23 was measured in the serum by ELISA. Results: IL-23 levels were positively correlated with the overall SLE disease activity as measured with the SLEDAI. Moreover, IL-23 correlated with the skin, renal domains of SLEDAI and arthritis but not with cytopenias or serositis. IL-23 did also correlate with anti-dsDNA antibody positivity and inversely correlated with C3 levels. We found no relationship between patients' demographics, prior disease manifestations, medications, or autoantibody profile and IL-23 levels. No immunomodulatory medication seemed to be affecting IL-23 levels suggesting that current medications used in SLE are not as effective in shutting down the IL-23/IL-17 axis. Conclusions: IL-23 levels track SLE disease activity mostly in the renal, skin and musculoskeletal domains. Our data suggest that IL-23 inhibitors may be helpful in combination with current standard of care in alleviating arthritis, renal and cutaneous manifestations of the disease.

Introduction: Cigarette or hookah smoking, as well as alcohol consumption and abuse, are considered to be the most common etiological factors for the onset of oral cavity diseases, such as changes on the lips, tongue, stomatopyrosis, glossopyrosis, candidiasis., Aim: Research aims to determine the harmful effect of smoking the hookah as well as other harmful factors on the oral health of the student population of the Faculty of Dentistry in Sarajevo., Methods: The fourth, fifth, and sixth-year students of the Faculty of Dentistry in Sarajevo participated in this cross-sectional study. All of them are systemically healthy and consume some harmful habits: smoking cigarettes, alcohol consumption, and hookah. All students participated in the study voluntarily and they signed informed consent before the clinical examination. All the subjects gave an extensive medical history which recorded all the data on oral hygiene, harmful habits, manner and length of consumption; they were also given a clinical examination of the oral mucosa and the periodontium, as well as determining periodontal indices, and oral tests that are used for diagnostic purposes. The data is entered into work charts specially designed for these purposes., Results: The results are statistically processed in the SPSS Statistics 21.0 program and are discussed along with the results of other authors, published in relevant databases., Conclusion: The conclusion consists of important facts that originate from the results and the discussion., Competing Interests: None declared., (© 2020 Sanja Hadzic, Mirjana Gojkov-Vukelic, Enes Pasic, Indira Mujic Jahic, Arma Muharemovic, Amina Huseinbegovic-Cengic.)

Abnormal T cell responses are central to the development of autoimmunity and organ damage in systemic lupus erythematosus. Following stimulation, naïve T cells undergo rapid proliferation, differentiation and cytokine production. Since the initial report, approximately two decades ago, that engagement of CD28 enhances glycolysis but PD-1 and CTLA-4 decrease it, significant information has been generated which has linked metabolic reprogramming with the fate of differentiating T cell in health and autoimmunity. Herein we summarize how defects in mitochondrial dysfunction, oxidative stress, glycolysis, glutaminolysis and lipid metabolism contribute to pro-inflammatory T cell responses in systemic lupus erythematosus and discuss how metabolic defects can be exploited therapeutically., Competing Interests: CONFLICTS OF INTEREST The authors declare that they have no conflicts of interest.

Th1 and Th17 are important in the pathogenesis of autoimmune diseases and they depend on glycolysis as a source of energy. T cell antigen receptor signaling phosphorylates a serine/threonine kinase, calcium/calmodulin-dependent protein kinase IV (CaMK4), and promotes glycolysis. Based on these findings we hypothesized that CaMK4 promotes glycolysis. Camk4-deficient CD4+ T cells and cells treated with a CaMK4 inhibitor had less glycolysis compared with their counterparts. Pull-down of CaMK4 and mass spectrometry identified pyruvate kinase muscle isozyme (PKM), the final rate-limiting enzyme in glycolysis, as a binding partner. Coimmunoprecipitation and Western blotting showed that CaMK4 interacts directly with PKM2. Camk4-deficient CD4+ T cells displayed decreased pyruvate kinase activity. Silencing or pharmacological inhibition of PKM2 reduced glycolysis and in vitro differentiation to Th1 and Th17 cells, while PKM2 overexpression restored Th17 cell differentiation. Treatment with a PKM2 inhibitor ameliorated experimental autoimmune encephalomyelitis and CD4+ T cells treated with PKM2 inhibitor or Pkm2-shRNA caused limited disease activity in an adoptive cell transfer model of experimental autoimmune encephalomyelitis. Our data demonstrate that CaMK4 binds to PKM2 and promotes its activity, which is requisite for Th1 and Th17 differentiation in vitro and in vivo. PKM2 represents a therapeutic target for T cell-dependent autoimmune diseases.

Purpose of Review: The standard treatment options for systemic lupus erythematosus (SLE) are focused on non-specific immunosuppression. Over the past few years, scientific studies and ongoing clinical trials have shifted the paradigm with rapid advances in developing biologics and small molecules. A number of monoclonal antibodies and small molecule inhibitors have been developed to target specific pathways involved in SLE. Many of these novel therapeutic agents are already being tested in clinical trials and they may 1 day reshape the landscape of SLE treatment. Herein we review potential future therapeutic options for SLE.

Laser ablation is recently suggested as a most effective and reliable technique for depigmentation of melanin hyperpigmented gingiva. To date, different lasers have been used for gingival depigmentation (CO 2 , diode, Nd:YAG, Er:YAG and Er,Cr:YSGG lasers). The use of Er:YAG laser for depigmentation of melanin hyperpigmented gingiva has gained increasing importance in recent years. The purpose of this study was to report removal of gingival melanin pigmentation using an Er:YAG laser in a literature review. The main outcomes, such as improvement of signs (clinical parameters of bleeding, erythema, swelling and wound healing), symptoms (pain) and melanin recurrence/repigmentation were measured. The literature demonstrated that depigmentation of gingival melanin pigmentation can be performed safely and effectively by Er:YAG laser resulting in healing and an esthetically significant improvement of gingival discoloration. Thus, Er:YAG laser seems to be safe and useful in melanin depigmentation procedure. However, the main issue in giving the final conclusion of the optimal Er:YAG laser use in melanin depigmentation is that, to date, studies are offering completely discrepant Er:YAG laser procedure protocols (complex settings of laser parameters), and different criteria for the assessment of depigmentation and repigmentation (recurrence), thus hampering the comparison of the results. Therefore, further studies are necessary to give an optimal recommendation on the use of Er:YAG laser in gingival melanin hyperpigmentation.

Introduction: One of the most important goals of periodontitis therapy is the elimination of deep periodontal pockets. In regenerative periodontal therapy, different types of bone grafts, membranes, growth factors, etc. are used to improve regeneration of lost periodontal tissue. The aim of this study was to evaluate the effect of surgical therapy supported by the use of bone replacement material in the treatment of deep intrabony pockets, compared to surgical treatment (flap surgery) without the use of bone replacement in advanced periodontitis., Methods and Materials: The study included 50 patients of both sexes with advanced periodontitis, divided into two groups. After initial periodontal therapy was performed, plaque index (PI), papillary bleeding index (PBI) were verified, and depth of periodontal pockets was measured in both groups. One group (group 1) of the patients underwent surgical therapy, open flap surgery, while the other group (group 2) underwent the same surgical treatment method (open flap surgery), during which bone defects were filled with bone replacement material., Results: The results showed that both group 1 and group 2 experienced improvements after periodontal surgical therapy. In group 1, there are no statistically significant changes in all three plaque index measurements (PI), while there has been a significant reduction in PI in group 2 following the surgery. For the PBI index, it was determined that there were statistically significant changes in values in group 1, both after surgical procedures and six months later, as well as in group 2. Statistical analysis of the results of the probing depth of pockets has shown that there are significant changes in the measurement of the depth of periodontal pocket one month after the surgery, as well as six months later, meaning that there has been a significant reduction in the depth of the periodontal pocket one month following the surgery as well as six months later, for both groups. However, we did not determine a statistically significant difference in the probing depth of pockets between these two groups., Conclusion: Six months after a surgical therapy, clinical parameters showed a reduction of the probing depth of the periodontal pocket in both examined groups. The use of bone replacement did not yield significantly better results in reducing the depth of probing compared to the standard flap surgery. We believe that future research should focus on testing the effectiveness of new regenerative methods and materials (bone replacements with various properties, membranes, and surgical methods) that will result in better treatment results with predictable outcomes., Competing Interests: • Authors’ contributions: Conception and design: MGV and SH; Acquisition, analysis and interpretation of data: MGV, SH and EP; Drafting the article: MGV and EP; Revising it critically for important intellectual content: MGV and SH.

Objective: The aim of this study was to assess the importance of early diagnosis of potentially malignant lesions in the prevention of oral cancer., Material and Methods: In order to achieve the set objectives, we selected our participant pool. Of the 340 patients who came to the initial examination at the Clinic for Oral Medicine and Periodontology, we selected 40 patients with potentially malignant oral lesions (PMOL) of both sexes and of different ages. After an extensive anamnesis and a clinical examination of all mucous membranes, we documented potentially malignant lesions, their localization, subjective and objective symptoms, duration of pathological lesion, and bad habits (smoking and alcohol). All lesions were colored with Toluidine blue, which indicates malignancy in 75% of cases. Patients who had a positive Toluidine blue staining test were sent to biopsy and pathohistological analysis., Results: The most common potentially malignant lesions are Lichen reticularis (25%), Lichen erosivus (20%), and Leukoplakia (15%). The most common localization of lesions is the buccal mucosa bilaterally (26%), buccal mucosa unilaterally (10%), and the lower lip (10%). The staining test with Toluidine blue was positive at 23% PMOLs. In patients with positive Toluidine staining findings, biopsy and pathohistological analysis were performed, which showed that 20% of all lesions are carcinoma (CIS, Baseocellular Carcinoma, Squamocellular Carcinoma), while 14% are mucosal epithelial dysplasia. Statistical analysis confirmed the significance of positive staining of Toluidine blue and Leukoplakia (Spearman's coefficient = 0.427, p = 0.006, N = 40), and statistically significant positive association of Squamocellular Carcinoma and Toluidine blue staining (Spearman's coefficient = 0.619, p = 0.000, N = 40)., Conclusion: Most oral cancers are caused by potentially malignant lesions, which is why a very detailed clinical examination with the visualization of pathological lesions is very important. Toluidine blue test can be an auxiliary tool for clinical diagnosis but does not replace the pathohistological finding. Biopsy and pathohistological findings are the gold standard in the diagnosis of oral cancers, as confirmed in our research., Competing Interests: • Conflict of interest: none declared.

Introduction: Dentine hypersensitivity is characterized by acute, sharp pain arising from the exposed dentine, most commonly in response to thermal, tactile, or chemical stimuli, and which cannot be linked to any other pathological changes in the tooth or the environment. Therapy uses various impregnating agents in the form of solutions or gels and, in more recent times, laser., Aim: The aim of this research was to examine the effects of treatment of hypersensitive dental cervix with diode laser., Materials and Methods: The study included 18 patients with 82 sensitive teeth. The degree of dentine hypersensitivity was evaluated by visual analogue scale (VAS), and the treatment was carried out by application of low-power diode laser over the span of three visits, which depended on the initial sensitivity., Results: There is a significant difference in VAS values measured at the onset of treatment (baseline) and immediately after the first laser treatment (t=9.275; p=0.000), after 7 days, after the second laser treatment (14 days) (t=7.085, p=0.000), as well as after 14 days and the third laser treatment (t=5.517, p=0.000), which confirms the effectiveness of this therapeutic procedure. The results showed a reduction of hypersensitivity in response to tactile stimulus with a probe after the third treatment, even with teeth whose value on the VAS was very high at the beginning of treatment (baseline)., Conclusion: Within the scope of the conducted study, laser therapy has provided extremely safe and effective results in the treatment of cervical dentine hypersensitivity.

Objective: Pregnancies in women with the antiphospholipid syndrome (APS) are frequently complicated by fetal loss and intrauterine growth restriction (IUGR). How circulating antiphospholipid antibodies (aPL) cause pregnancy complications in APS is poorly understood. We sought to determine whether the low-density lipoprotein receptor family member apolipoprotein E receptor 2 (ApoER2) mediates trophoblast dysfunction and pregnancy complications induced by aPL., Methods: Placental and trophoblast ApoER2 expression was evaluated by immunohistochemistry and immunoblotting. Normal human IgG and aPL were purified from healthy individuals and APS patients, respectively. The role of ApoER2 in aPL-induced changes in trophoblast proliferation and migration and in kinase activation was assessed using RNA interference in HTR-8/SVneo cells. The participation of ApoER2 in aPL-induced pregnancy loss and IUGR was evaluated in pregnant ApoER2(+/+) and ApoER2(-/-) mice injected with aPL or normal human IgG., Results: We found that ApoER2 is abundant in human and mouse placental trophoblasts and in multiple trophoblast-derived cell lines, including HTR-8/SVneo cells. ApoER2 and its interaction with the cell surface protein β2 -glycoprotein I were required for aPL-induced inhibition of cultured trophoblast proliferation and migration. In parallel, aPL antagonism of Akt kinase activation by epidermal growth factor in trophoblasts was mediated by ApoER2. Furthermore, in a murine passive-transfer model of pregnancy complications of APS, ApoER2(-/-) mice were protected from both aPL-induced fetal loss and aPL-induced IUGR., Conclusion: ApoER2 plays a major role in the attenuation of trophoblast function by aPL, and the receptor mediates aPL-induced pregnancy complications in vivo in mice. ApoER2-directed interventions can now potentially be developed to combat the pregnancy complications associated with APS., (© 2015, American College of Rheumatology.)

Introduction: Periodontal disease belongs to a group of diseases with more than one cause, it is a disease of a multifactorial etiology. Although bacteria are the main cause of the disease, immunoinflammatory reaction of the host is responsible for the majority of destructive changes in periodontal tissue. The main issue in the evaluation of the success of periodontal therapy is the pluralism of the bacteria and their dynamic changes during the duration, on the one hand, and the possible inaccuracy of classical microbiological analysis in determination of the dominant role of a microorganism, or the success of its reduction or elimination, on the other. Thanks to advances of microbiology and technological development, it is possible to make an assessment of specific microorganisms in a large number of samples of sub-gingival plaque with extreme precision, using checkerboard DNA-DNA hybridization and method of polymerase chain reaction (PCR). The development of laser technology and the discovery of its significant antimicrobial effects have introduced and presented this treatment modality as a possible auxiliary method of periodontitis treatment., Materials and Methods: The sample for the study estimating the efficiency of application of diode lasers in the reduction of periodontal pockets consisted of 1164 periodontal pockets in 24 subjects of both sexes. For laser irradiation of periodontal pockets a diode laser was used, a low-power laser (SmilePro 980, Biolitec, Germany), working in a mode precisely tuned for treatment of periodontal pockets. All subjects underwent: general anamnesis, periodontal status, and orthopantogram radiograph analysis. Following a standard periodontal preparation, a sample of subgingival plaque was collected for molecular-biological analysis (real-time PCR method) prior to laser irradiation of periodontal pockets, immediately following the irradiation, and during the control examination 3 months after irradiation., Results: The results of the molecular-biological analysis of target periodontal pathogens Actinobacillus (Aggregatibacter) actinomycetemcomitans (AA) and Porphyromonas gingivalis (PG) isolated from periodontal pockets prior to laser irradiation, immediately after laser irradiation, and at the control examination after 3 months were processed statistically (using real-time PCR method). The results showed that there was a statistically significant decrease in CT values for the tested bacteria immediately after treatment and the control examination, compared with the level of CT values for the same bacteria before treatment., Conclusions: Based on the obtained results, we concluded that diode laser irradiation reduces the number of active periodontal pathogens. We believe that the use of diode lasers, as a supplementary method in the treatment of periodontal disease, is extremely useful and efficient, and can be recommended as part of standard clinical practice.

Buerger's disease (BD) is a relatively rare thrombotic, occlusive and non-atherosclerotic clinical syndrome of unknown etiology. In recent years, numerous epidemiological studies confirmed the strong association between chronic anaerobic periodontal infection and development of cardiovascular diseases, including BD. Therefore, the aim of this study is to clarify association between periodontal pathogens and Buerger's disease. Confirmation of presence and identification of periopathogens in patients with BD can be considered crucial in developing novel therapies for BD. Further, periodontal therapy will lead to eventual improvement of BD patients' condition.

The Goal: The goal of this study was to determine the effect of psychoactive substances (drugs) on the presence and frequency of oral Candida species and Candida dubliniensis., Materials and Methods: For the purpose of achieving the set goals, we chose a sample. Sixty bed-ridden patients from the Institute for Alcoholism and Other Addictions in Sarajevo Canton, both males and females between 18 and 60 years of age, were included in the research and assigned to two different groups (alcohol addicts and opiate addicts). After extensive anamnesis and a clinical examination, samples of oral epithelia were taken for microbiological identification. Two confirmatory methods were used for the identification of Candida species: the blastesis test and cultivation in a chromatophilic medium (Chrom agar). A yeast assimilation test (API test) was used for the identification of non-albicans Candida. A separate test was used to identify Candida dubliniensis (PAL agar)., Results: The results of the microbiological analysis confirmed the frequency of Candida albicans (43%) in psychoactive substance addicts, as well as an increase in non-albicans Candida regardless of the type of addiction (34%). The presence of Candida dubliniensis was proven in psychoactive substance addicts (23%) and it was confirmed that the frequency of bacterial adherence of Candida dubliniensis is directly proportional to the duration of the drug-addiction., Conclusion: The abuse of psychoactive substances has an effect on the frequency of albicans and non-albicans species of oral Candida. Based on the findings, we have concluded that psychoactive substances (opiates and alcohol) lead to an increase in oral Candida dubliniensis regardless of the type of addictions.

Cholinergic neural output has been shown to modulate innate immune responses to infection, injury and ischemia through stimulation of α7 nicotinic acetylcholine receptors (α7nAChR) on mononuclear phagocytes. We tested the hypothesis that cholinergic neurotransmitters, similar to those released through activation of a neural reflex, regulate responses to products of the adaptive immune system, specifically immune complex (IC)-mediated activation of effector cells. In this study, we show that stimulation of α7nAChR on human polymorphonuclear neutrophils (PMNs) and blood mononuclear phagocytes in vitro attenuates C5aR- and FcγR-triggered generation of reactive oxygen species, expression of leukocyte markers involved in cell recruitment and adhesion, and release of TNF-α and other proinflammatory cytokines. We show that this pathway is operative in vivo. Ligation of cholinergic receptors blunts IC-triggered responses in the reverse peritoneal Arthus reaction in mice. The selective 7nAChR agonist GTS21 decreased PMN accumulation and release of cytokines and chemokines at sites of IC deposition. In addition, mice lacking α7nAChR had exaggerated responses to reverse peritoneal Arthus reaction characterized by increased infiltration of PMNs and elevated of levels of TNF-α and CXCL1 in peritoneal fluid compared with wild-type mice. Taken together, these findings suggest that cholinergic output has the potential to exert tonic inhibitory activity that dampens responses to ICs and C5a and thus may be a target to minimize tissue damage in autoimmune diseases.

The most common oral solitary pigmented lesion is the dental amalgam tattoo. It occurs as a result of colouring of the tissue by alien pigment which was administered intra or subepidermaly either intentionally or accidentally. The most common material used for the colouring of the oral mucosa is amalgam from amalgam fillings and metal particles from prosthetic restorations which are absorbed accidentally. The oral mucosa tattoos are most often found in the area of the marginal gingiva or the buccal mucosa. The metal particles may accidentally reach the area of the oral mucosa during various dentistry interventions. The therapy most often involves surgical intervention with excisional biopsy while in the recent period the low power laser therapy has provided exceptional results. The aim of the paper was to present the successful removal of the oral mucosa tattoo in a single visit.

Objective: To construct a humanized mouse model of systemic lupus erythematosus (SLE) that resembles the human disease in order to define the pathophysiology and targets for treatments., Methods: We infused peripheral blood mononuclear cells (PBMCs) from SLE patients into BALB- RAG-2-/- IL-2Rγ-/- double-knockout (DKO) mice, which lack T cells, B cells, and natural killer cells. PBMCs from 5 SLE patients and 4 normal donors were infused intravenously/intraperitoneally at a density of 3-5×10(6) cells per animal into nonirradiated 4-5-week-old mice. We evaluated the engraftment of human CD45+ cells and monitored the plasma levels of human IgG, anti-double-stranded DNA (anti-dsDNA) antibody, and anticardiolipin antibody (aCL), as well as proteinuria and kidney histology., Results: There was 100% successful engraftment in 40 DKO mice infused with human PBMCs. In the PBMC fraction from SLE PBMC-infused DKO (SLE-DKO) mice and normal donor PBMC-infused DKO (ND-DKO) mice, an average of 41% and 53% human CD45+ cells, respectively, were observed at 4 weeks postengraftment, with 70-90% CD3+ cells. There were fewer CD3+CD4+ cells (mean±SEM 5.5±2.1%) and more CD3+CD8+ cells (79.4±3.6%) in the SLE-DKO mice as in the SLE patients from which the PBMCs were derived. CD19+ B cells and CD11c+ monocytic cells were found in the spleen, lung, liver, and bone marrow. There was no significant difference in plasma levels of human IgG and anti-dsDNA antibodies between SLE-DKO and ND-DKO mice. Levels of aCL were significantly higher in all SLE-DKO mice infused with PBMCs from an SLE patient who had high titers of aCL. SLE-DKO mice had proteinuria, human IgG deposits in the kidneys, and a shorter life span. In SLE-DKO mice engrafted with PBMCs from the aCL-positive patient, we found microthrombi and infiltration of CD3+, CD8+, and CD19+ cells in the glomeruli, recapitulating the human antiphospholipid syndrome in these mice., Conclusion: We established a novel humanized SLE-DKO mouse exhibiting many of the immunologic and clinical features of human SLE., (Copyright © 2011 by the American College of Rheumatology.)

Cheilitis granulomatosa is a rare disease characterised by the recurrent labial swelling of one or both lips with the possibility of the condition to remain on a permanent basis. The disease may appear independently or it may be linked to a paralysis such as the facial and lingua plicata which then characteristic of the Melcersson-Rosenthal Syndrome. The aim of this paper is to show a case of a patient with the granulomatosae cheilitis and lingua plicata whose reaction to the Chymoral Forte treatment was excellent.