THE THERAPEUTIC TREATMENT OF PEPITEM INCREASES THE PROTEIN EXPRESSION OF SIRT1 IN A MOUSE MODEL OF EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS (EAE) AS A MODEL FOR HUMAN MS

Objective: To investigate the effect of the prophylactic and therapeutic treatment of the immunopeptide PEPITEM on the protein expression of SIRT1 in a mouse model of experimental autoimmune encephalomyelitis (EAE) as a model for human MS.   Methods: Using C57BL/6 female mice, we dosed the PEPITEM in the EAE model via intraperitoneal injections either prophylactically or therapeutically. The disease was induced using MOG35-55 and complete Freund's adjuvants augmented with pertussis toxin. The EAE score was recorded daily until the end of the experiment (21 days). A Western blot analysis was performed on the brain lysate to measure the protein concentration of SIRT1. Results: The therapeutic treatment with PEPITEM increased the protein expressions of SIRT1 on the EAE mice whereas the prophylactic injections did not affect the protein expression of SIRT1. Conclusion: Collectively, the therapeutic treatment with PEPITEM suggesting anti-inflammatory effect of PEPITEM on the brain damage in EAE mice which offers a novel and safe strategy for drug therapy in MS, opening new avenues for research and treatment

Characterising the PEPITEM pathway in patients with atherosclerosis

Atherosclerosis is an asymptomatic disease which is regarded as one of the most fatal diseases. However, the mechanism of the immune response is not well understood. There is accumulated evidence supporting the idea that inflammatory response initiates the disease. A new novel peptide has been discovered in our lab which down-regulates T cell recruitment during inflammation called PEPITEM (Peptide Inhibitor of Trans Endothelial Migration). We are interested in testing the action of PEPITEM on PBL isolated from atherosclerosis patients. We first demonstrated that PEPITEM did not affect the levels of adhesion of PBL from either diseased or healthy donors. Interestingly however, we did observe that PBL isolated from atherosclerosis patients adhere more readily than those isolated from healthy control subjects. Therefore, we studied the surface expression of certain adhesion molecules and chemokine receptors on the PBL of atherosclerosis patients. We found significantly higher surface expression of Beta-receptor family (Beta-1 and Beta-2) and PSGL-1 receptors in some PBL subsets in atherosclerosis patients. In addition, we looked at the effect of PEPITEM and adiponectin (AQ) treatment on the migration of PBL and we revealed for the first time based on our knowledge that there was no effect of treatment on PBL isolated from atherosclerosis patients. These observations will contribute to understanding the potential therapeutic applications of PEPITEM on atherosclerosis

The usage, self-presentation via Facebook, and its psychological and sociological consequences towards Saudi Arabia University students / Abdullah Ali Alassiri

Prompted by the widespread saturation of Facebook usage in Saudi Arabia, among university students to socialize with online members, this study investigated the usage, self-presentation, psychological and sociological consequences of the Facebook social networking site among undergraduate students in Saudi Arabia. The problem statements of this study were addressed by answering the seven research questions: 1) What motivation does undergraduate students have for joining Facebook? 2) How undergraduate students do consume Facebook? 3) In what condition does undergraduate students need Facebook? 4) How do undergraduate students manage their self-presentation via Facebook? 5) What are the experiences obtained by the undergraduate students from Facebook psychologically? 6) What are the experiences obtained by the undergraduate students from Facebook sociologically? 7) How have Facebook activities affected the lifestyle of the undergraduate students? The research questions were answered by analysing in-depth interview data collected from twenty male undergraduate students between the ages of 18 and 24 years selected from King Saud University (KSU) and King Khalid University (KKU) Saudi Arabia. Using thematicanalysis, informants data were coded 'Rl to R20\ validated and was transcribed to minimize error from translating into the research items from Arabic back to English Language. Using purposive sampling method informant perspective within the research context were explored. Data collection confined to motivations students have for engaging in online activities, self-presentation, psychological and sociological consequences to their everyday life was investigated based on the theoretical and philosophical perspective underpinnings media and gratification paradigm and social influence theory. The research findings contributed to the development of important research themes that supported the development of a new research framework. Based on the analysis, all the research questions were answered. The findings foe this study showed that the students use Facebook for the prupose of interacting with others, getting information and as knowledge sources. In terms of self-presentation, this study revealed that the students portray theselves in real and not fake image while socializing with others.psychological and sociological consequences from the usage of Facebook are recorded ranging from cheerful to stress and from lonliness to having many friends. As a conclusion, this study conclusively drawn that Facebook is a very persuasive medium of communication among the University students in Saudi Arabia that bridges across socio-cultural boundaries and unites students to interact as a community

Mycotic aortic aneurysm due to brucellosis

Brucellosis is a multisystem zoonotic disease. Mycotic aneurysm due to Brucella is rare and has no clear management approach. Here, we present two cases of mycotic aortic aneurysm due to Brucella. The first patient was treated with surgical resection of a symptomatic infrarenal abdominal aortic aneurysm combined with lifelong doxycycline and rifampicin. The second patient improved with conservative treatment including a 6-month course of antibiotics and regular clinical and radiologic monitoring. Through these cases, we hope to draw attention to this serious adverse effect of Brucella and the importance of management of its local arterial complications, especially in endemic areas

Utility of active MMP-8 as a test biomarker in periodontal and peri-implant diseases : diagnosis, prevention and treatment outcomes

Active Matrix Metalloproteinase (aMMP-8), collagenase-2, is a key mediator in the destruction of tissues seen in periodontitis and peri-implantitis. It can be detected in oral fluid samples, including gingival crevicular fluid (GCF), saliva, mouth rinse and peri-implant sulcular fluid (PISF). Active MMP-8, which is mainly expressed by neutrophils, can degrade almost all extracellular matrix and basement membrane components; it is causes particularly high levels of degradation in type I collagen, which is present in periodontal ligaments. In the first part of this thesis, we demonstrated that during an experimental gingivitis study aMMP-8 was not detectable in saliva. Therefore, this study confirms the evidence; aMMP-8 is detected in periodontitis. Simultaneously, the lateral-flow chairside aMMP-8 immunotests, PerioSafe and ImplantSafe with the Oralyzer reader, which are based on Professor Timo Sorsa’s research, were introduced and validated to analyse the levels of aMMP-8 in mouth rinse or PISF. Thus, the last parts of the thesis evaluate the accuracy and reliability of these developed tools: PerioSafe and ImplantSafe/Oralyzer, and whether they could provide an easy-to-use and quick way of identifying periodontitis and peri-implantitis. Our results indicated that the tools were successful in their detection. They were also very accurate in terms of both sensitivity and specificity with clinical periodontal parameters, such as bleeding on probing (BOP) and plaque index (PI). In addition, study V has investigated the effectiveness of sub-antimicrobial doses of doxycycline (SDD) treatment when combined with non-surgical periodontal therapy, and their effect on potential GCF biomarkers in periodontal tissue destruction over a period of twelve months. The analysed biomarkers were MMP-8, -9, -13, myeloperoxidase (MPO), osteoprotegerin (OPG), and tartrate-resistant acid phosphatase 5 (TRAP 5), which were determined by various immunofluorometric analyses (IFMA) and enzyme-linked immunosorbent assays (ELISA). The results demonstrated reduced GCF levels in two MMPs that most commonly associated with periodontitis; MMP-8 and -9, and MPO, which potentially causes oxidative activation in them. However, MMP-13 and TRAP could be detected in the relevant GCF samples, whereas the OPG levels also decreased significantly as a result of adjunctive SDD therapy. This thesis showed the reliability of these tools, PerioSafe and ImplantSafe/Oralyzer, for the successful detection, prediction and monitoring of the progress of periodontitis and peri-implantitis, and their response to treatment. Additionally, we delved further in to the beneficial effects of sub-antimicrobial doses of doxycycline therapy.Active Matrix Metalloproteinase (aMMP-8), collagenase-2, is a key mediator in the destruction of tissues seen in periodontitis and peri-implantitis. It can be detected in oral fluid samples, including gingival crevicular fluid (GCF), saliva, mouth rinse and peri-implant sulcular fluid (PISF). Active MMP-8, which is mainly expressed by neutrophils, can degrade almost all extracellular matrix and basement membrane components; it is causes particularly high levels of degradation in type I collagen, which is present in periodontal ligaments. In the first part of this thesis, we demonstrated that during an experimental gingivitis study aMMP-8 was not detectable in saliva. Therefore, this study confirms the evidence; aMMP-8 is detected in periodontitis. Simultaneously, the lateral-flow chairside aMMP-8 immunotests, PerioSafe and ImplantSafe with the Oralyzer reader, which are based on Professor Timo Sorsa’s research, were introduced and validated to analyse the levels of aMMP-8 in mouth rinse or PISF. Thus, the last parts of the thesis evaluate the accuracy and reliability of these developed tools: PerioSafe and ImplantSafe/Oralyzer, and whether they could provide an easy-to-use and quick way of identifying periodontitis and peri-implantitis. Our results indicated that the tools were successful in their detection. They were also very accurate in terms of both sensitivity and specificity with clinical periodontal parameters, such as bleeding on probing (BOP) and plaque index (PI). In addition, study V has investigated the effectiveness of sub-antimicrobial doses of doxycycline (SDD) treatment when combined with non-surgical periodontal therapy, and their effect on potential GCF biomarkers in periodontal tissue destruction over a period of twelve months. The analysed biomarkers were MMP-8, -9, -13, myeloperoxidase (MPO), osteoprotegerin (OPG), and tartrate-resistant acid phosphatase 5 (TRAP 5), which were determined by various immunofluorometric analyses (IFMA) and enzyme-linked immunosorbent assays (ELISA). The results demonstrated reduced GCF levels in two MMPs that most commonly associated with periodontitis; MMP-8 and -9, and MPO, which potentially causes oxidative activation in them. However, MMP-13 and TRAP could be detected in the relevant GCF samples, whereas the OPG levels also decreased significantly as a result of adjunctive SDD therapy. This thesis showed the reliability of these tools, PerioSafe and ImplantSafe/Oralyzer, for the successful detection, prediction and monitoring of the progress of periodontitis and peri-implantitis, and their response to treatment. Additionally, we delved further in to the beneficial effects of sub-antimicrobial doses of doxycycline therapy

Adjunctive Effects of a Sub-Antimicrobial Dose of Doxycycline on Clinical Parameters and Potential Biomarkers of Periodontal Tissue Catabolism

Objectives: The aim of the present randomized, double-blind, placebo-controlled, parallel-arm study was to examine the effectiveness of a sub-antimicrobial dose of doxycycline (SDD) in combination with nonsurgical periodontal therapy, compared to nonsurgical periodontal therapy alone, on potential gingival crevicular fluid (GCF) biomarkers of periodontal tissue catabolism related to the clinical outcomes over a 12-month period. Materials and Methods: GCF was collected and clinical parameters were recorded from 30 periodontitis patients randomized either to an SDD or placebo group. The SDD group received SDD (20 mg) b.i.d for 3 months plus scaling and root planing (SRP), while the placebo group was given placebo capsules b.i.d for 3 months plus SRP. The patients were evaluated every 3 months during the 12-month study period. At each visit, clinical parameters and GCF sampling were repeated. Matrix metalloproteinase (MMP)-8, MMP-9, MMP-13, myeloperoxidase (MPO), osteoprotegerin (OPG), and tartrate-resistant acid phosphatase-5 (TRAP-5) were determined by IFMA and ELISA. Results: Significant improvements were observed in all clinical parameters in both groups over 12 months (p < 0.0125) while the SDD group showed significantly better reduction in gingival index (GI) and pocket depth and a gain in clinical attachment compared to the placebo group (p < 0.05). GCF MMP-8 and OPG levels significantly reduced in the SDD group compared to baseline (p < 0.05). GCF MMP-9 significantly decreased in both groups compared to baseline (p < 0.05). GCF MPO significantly decreased at 3 and 9 months in the SDD group, while it significantly decreased at 6 months in the placebo group (p < 0.05). TRAP and MMP-13 could be detected in none of the samples. Conclusions: The present results indicate that three months of adjunctive usage of SDD to nonsurgical periodontal therapy compared to nonsurgical periodontal therapy alone in periodontitis patients results in further improvement of clinical periodontal parameters and GCF markers of periodontal tissue breakdown over a 12-month period. Beneficial effects of adjunctive SDD therapy is likely to be related to the reduced levels of two major periodontitis-associated MMPs, MMP-8 and -9, and their potential oxidative activator MPO

Adjunctive Effects of a Sub-Antimicrobial Dose of Doxycycline on Clinical Parameters and Potential Biomarkers of Periodontal Tissue Catabolism

Objectives: The aim of the present randomized, double-blind, placebo-controlled, parallel-arm study was to examine the effectiveness of a sub-antimicrobial dose of doxycycline (SDD) in combination with nonsurgical periodontal therapy, compared to nonsurgical periodontal therapy alone, on potential gingival crevicular fluid (GCF) biomarkers of periodontal tissue catabolism related to the clinical outcomes over a 12-month period. Materials and Methods: GCF was collected and clinical parameters were recorded from 30 periodontitis patients randomized either to an SDD or placebo group. The SDD group received SDD (20 mg) b.i.d for 3 months plus scaling and root planing (SRP), while the placebo group was given placebo capsules b.i.d for 3 months plus SRP. The patients were evaluated every 3 months during the 12-month study period. At each visit, clinical parameters and GCF sampling were repeated. Matrix metalloproteinase (MMP)-8, MMP-9, MMP-13, myeloperoxidase (MPO), osteoprotegerin (OPG), and tartrate-resistant acid phosphatase-5 (TRAP-5) were determined by IFMA and ELISA. Results: Significant improvements were observed in all clinical parameters in both groups over 12 months (p < 0.0125) while the SDD group showed significantly better reduction in gingival index (GI) and pocket depth and a gain in clinical attachment compared to the placebo group (p < 0.05). GCF MMP-8 and OPG levels significantly reduced in the SDD group compared to baseline (p < 0.05). GCF MMP-9 significantly decreased in both groups compared to baseline (p < 0.05). GCF MPO significantly decreased at 3 and 9 months in the SDD group, while it significantly decreased at 6 months in the placebo group (p < 0.05). TRAP and MMP-13 could be detected in none of the samples. Conclusions: The present results indicate that three months of adjunctive usage of SDD to nonsurgical periodontal therapy compared to nonsurgical periodontal therapy alone in periodontitis patients results in further improvement of clinical periodontal parameters and GCF markers of periodontal tissue breakdown over a 12-month period. Beneficial effects of adjunctive SDD therapy is likely to be related to the reduced levels of two major periodontitis-associated MMPs, MMP-8 and -9, and their potential oxidative activator MPO

Active MMP-8 (aMMP-8) as a Grading and Staging Biomarker in the Periodontitis Classification

The aim of this study was to investigate the utility of incorporating active matrix metalloproteinase-8 (aMMP-8) as a biomarker into the new periodontitis classification system (stage/grade) presented in 2018. This study included 150 Greek adults aged 25–78, of whom 74 were men and 76 women. Participants were tested with an aMMP-8 point-of-care mouthrinse test, after which a full-mouth clinical examination was performed to assess their periodontal and oral health. The aMMP-8 levels in mouthrinse were significantly lower among healthy patients compared with patients in more severe periodontitis stages and grades (Kruskal–Wallis test and Dunn–Bonferroni test for pairwise post-hoc comparisons; p < 0.01 and p < 0.05, respectively). Furthermore, aMMP-8 levels were less correlated with plaque levels than bleeding on probing (BOP) (Spearman’s rho = 0.269, p < 0.001; Spearman’s rho = 0.586, p < 0.001); respectively). Thus, aMMP-8 was more robust to the confounding effects of oral hygiene than traditional periodontal parameter bleeding on probing. The aMMP-8 point-of-care mouthrinse test can be utilized as an adjunctive and preventive diagnostic tool to identify periodontal disease, classified by stage and grade, and ongoing periodontal breakdown chairside in clinical practice in only 5 min. Overall, integrating aMMP-8 into the new periodontitis classification system seems beneficial

Stem Cell Transplantation in Pediatric Patients with Myelodysplastic Syndrome at a Single Institution

In MDS, the bone marrow produces abnormal, immature blood cells called blast cells. Imprecise, in half of pediatric MDS, blast count is normal. A retrospective observational study was conducted to review the outcome of our HCT in pediatric patients with MDS. Record of 35 MDS patients after BMT, 1993-2016, were reviewed. Median age at transplant was 4 yrs (0.8-14.8) and median time to transplant from diagnosis 8.1 (2.3-102.5) months. TRM was 17.1% (6); [low risk (LR) = 5 (19.2%) and high risk (HR) = 1 (11.1%)] MDS group succumbed within first 100 days. The rest were fully engrafted; [low risk = 21 (72.4%) and high risk = 8 (27.6%)]. Primary and secondary graft failure was observed in one patient each (2.9%). VOD was seen in 2 patients (5.7%) and 5 (14.3%) had hemorrhagic cystitis. With a median follow-up of 112.4 months and 12 events of mortality, 3-years OS was 68.1% ± 8.0%. No significant risk factor including age, time to transplant, disease risk group, gender, conditioning regimen, source of stem cells, or a GvHD through uni- or multi-variable analyses were found to be associated with OS. Bu/Cy/±ATG conditioning regimen showed a trend of superiority for OS and EFS in our small series. The relapse incidence in our cohort was 11.5% in LR MDS

Active MMP-8 point-of-care (PoC)/chairside enzyme-test as an adjunctive tool for early and real-time diagnosis of peri-implantitis

Objective: The aim of this study was to investigate the utility of the active matrix metalloproteinase (aMMP-8)-point-of-care (PoC) test as a quantitative real-time chair-side diagnostic tool for peri-implant diagnosis, as well as assess the potentially developing and ongoing risk relative to the traditional clinical methods. Background: Current peri-implant and periodontal disease diagnoses rely on clinical arid radiological examinations. This case-control study investigated the applicability of aMMP-8-PoC immunotest for quantitative real-time diagnosis and monitoring of dental implants in health and disease. Methods: Sixty-eight patients visiting a specialist clinic for maintenance following dental implant placement underwent assessment of their peri-implant health. aMMP-8-PoC peri-implant sulcular fluid (PISF) lateral-flow immunotests were performed using ImplantSafe (R) technology quantitated by ORALyzer (R). In addition, the PISF samples were analyzed for total MMP-8, calprotectin, and interleukin (IL)-6 by enzyme-linked immunosorbent assays (ELISA), aMMP-8 by western immunoblot, and MMP-2 and MMP-9 by gelatin zymography. Results: The aMMP-8-PoC test promptly recorded and reflected peri-implant disease, differentiating it clearly from health. X-ray findings (bone loss > 2 mm), peri-implant pocket depth >= 3 mm, and bleeding on probing were significantly more prevalent among implants positive for the aMMP-8-PoC test. aMMP-8/ORALyzer analysis was more precise in recording disease than total MMP-8, calprotectin, IL-6, MMP-2, and MMP-9. Conclusions: The aMMP-8-PoC test can be conveniently implemented to alert for and detect active collagenolysis affecting peri-implant tissues, both in the early and advanced stages of the disease. Active and fragmented MMP-8 exhibits a strong and significant association with peri-implantitis as compared to total MMP-8 arid other biomarkers and can be utilized as the POC/chairside biomarker of choice in the new classification of peri-implantitis.Peer reviewe