Search results for: psoriatic arthritis
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 143

Search results for: psoriatic arthritis

83 Association of Musculoskeletal and Radiological Features with Clinical and Serological Findings in Systemic Sclerosis: A Single-Centre Registry Study

Authors: Nasrin Azarbani

Abstract:

Aim: Systemic sclerosis (SSc) is a chronic connective tissue disease with the clinical hallmark of skin thickening and tethering. Correlation of musculoskeletal features with other parameters should be considered in SSc patients. Methods: We reviewed the records of all patients who had more than one visit and standard anteroposterior radiography of hand. We used univariate analysis, and factors with p<0.05 were included in logistic regression to find out dependent factors. Results: Overall, 180 SSc patients were enrolled in our study, 161 (89.4%) of whom were women. Median age (IQR) was 47.0 years (16), and 52% had diffuse subtype of the disease. In multivariate analysis, tendon friction rubs (TFRs) was associated with the presence of calcinosis, muscle tenderness, and flexion contracture (FC) on physical examination (p<0.05). Arthritis showed no differences in the two subtypes of the disease (p=0.98), and in multivariate analysis, there were no correlations between radiographic arthritis and serological and clinical features. The radiographic results indicated that disease duration correlated with joint erosion, acro-osteolysis, resorption of distal ulna, calcinosis and radiologic FC (p< 0.05). Acro-osteolysis was more frequent in the dcSSc subtype, TFRs, and anti-TOPO I antibody. Radiologic FC showed an association with skin score, calcinosis and haematocrit <30% (p<0.05). Joint flexion on radiography was associated with disease duration, modified Rodnan skin score, calcinosis, and low haematocrit (P<0.01). Conclusion: Disease duration was a main dependent factor for developing joint erosion, acro-osteolysis, bone resorption, calcinosis, and flexion contracture on hand radiography. Acro-osteolysis presented in the severe form of the disease. Acro-osteolysis was the only dependent variable associated with bone demineralization.

Keywords: sclerosis, disease subsets, joint erosion, musculoskeletal

Procedia PDF Downloads 41
82 Evaluation of Anti-Arthritic Activity of Eulophia ochreata Lindl and Zingiber cassumunar Roxb in Freund's Complete Adjuvant Induced Arthritic Rat Model

Authors: Akshada Amit Koparde, Candrakant S. Magdum

Abstract:

Objective: To investigate the anti-arthritic activity of chloroform extract and Isolate 1 of Eulophia ochreata Lindl and dichloromethane extract and Isolate 2 of Zingiber cassumunar Roxb in adjuvant arthritic (AA) rat model induced by Freund’s complete adjuvant (FCA). Methods: Forty two healthy albino rats were selected and randomly divided into six groups. Freund’s complete adjuvant (FCA) was used to induce arthritis and then treated with chloroform extract, isolate 1 and dichloromethane extract, isolate 2 for 28 days. The various parameters like paw volume, haematological parameters (RBC, WBC, Hb and ESR), were studied. Structural elucidation of active constituents isolate 1 and isolate 2 from Eulophia ochreata Lindl and Zingiber cassumunar Roxb will be done using GCMS and H1NMR. Results: In FCA induced arthritic rats, there was significant increase in rat paw volume whereas chloroform extract and Isolate 1 of Eulophia ochreata Lindl and dichloromethane extract and Isolate 2 of Zingiber cassumunar Roxb treated groups showed strong significant reduction in paw volume. The altered haematological parameters in the arthritic rats were significantly recovered to near normal by the treatment with extracts at the dose of 200 mg/kg. Further histopathological studies revealed the anti-arthritic activity of Eulophia ochreata Lindl and Zingiber cassumunar Roxb by preventing cartilage and bone destruction of the arthritic joints of AA rats. Conclusion: Extracts and isolates of Eulophia ochreata Lindl and Zingiber cassumunar Roxb have shown anti-arthritic activity. Decrease in paw volume and normalization of haematological abnormalities in adjuvant induced arthritic rats is significantly seen in the experiment. Further histopathological studies confirmed the anti-arthritic activity of Eulophia ochreata Lindl and Zingiber cassumunar Roxb.

Keywords: arthritis, Eulophia ochreata Lindl, Freund's complete adjuvant, paw volume, Zingiber cassumunar Roxb

Procedia PDF Downloads 141
81 Factors Associated with Hand Functional Disability in People with Rheumatoid Arthritis: A Systematic Review and Best-Evidence Synthesis

Authors: Hisham Arab Alkabeya, A. M. Hughes, J. Adams

Abstract:

Background: People with Rheumatoid Arthritis (RA) continue to experience problems with hand function despite new drug advances and targeted medical treatment. Consequently, it is important to identify the factors that influence the impact of RA disease on hand function. This systematic review identified observational studies that reported factors that influenced the impact of RA on hand function. Methods: MEDLINE, EMBASE, CINAL, AMED, PsychINFO, and Web of Science database were searched from January 1990 up to March 2017. Full-text articles published in English that described factors related to hand functional disability in people with RA were selected following predetermined inclusion and exclusion criteria. Pertinent data were thoroughly extracted and documented using a pre-designed data extraction form by the lead author, and cross-checked by the review team for completion and accuracy. Factors related to hand function were classified under the domains of the International Classification of Functioning, Disability, and Health (ICF) framework and health-related factors. Three reviewers independently assessed the methodological quality of the included articles using the quality of cross-sectional studies (AXIS) tool. Factors related to hand function that was investigated in two or more studies were explored using a best-evidence synthesis. Results: Twenty articles form 19 studies met the inclusion criteria from 1,271 citations; all presented cross-sectional data (five high quality and 15 low quality studies), resulting in at best limited evidence in the best-evidence synthesis. For the factors classified under the ICF domains, the best-evidence synthesis indicates that there was a range of body structure and function factors that were related with hand functional disability. However, key factors were hand strength, disease activity, and pain intensity. Low functional status (physical, emotional and social) level was found to be related with limited hand function. For personal factors, there is limited evidence that gender is not related with hand function; whereas, conflicting evidence was found regarding the relationship between age and hand function. In the domain of environmental factors, there was limited evidence that work activity was not related with hand function. Regarding health-related factors, there was limited evidence that the level of the rheumatoid factor (RF) was not related to hand function. Finally, conflicting evidence was found regarding the relationship between hand function and disease duration and general health status. Conclusion: Studies focused on body structure and function factors, highlighting a lack of investigation into personal and environmental factors when considering the impact of RA on hand function. The level of evidence which exists was limited, but identified that modifiable factors such as grip or pinch strength, disease activity and pain are the most influential factors on hand function in people with RA. The review findings suggest that important personal and environmental factors that impact on hand function in people with RA are not yet considered or reported in clinical research. Well-designed longitudinal, preferably cohort, studies are now needed to better understand the causality between personal and environmental factors and hand functional disability in people with RA.

Keywords: factors, hand function, rheumatoid arthritis, systematic review

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80 Development of Ketorolac Tromethamine Encapsulated Stealth Liposomes: Pharmacokinetics and Bio Distribution

Authors: Yasmin Begum Mohammed

Abstract:

Ketorolac tromethamine (KTM) is a non-steroidal anti-inflammatory drug with a potent analgesic and anti-inflammatory activity due to prostaglandin related inhibitory effect of drug. It is a non-selective cyclo-oxygenase inhibitor. The drug is currently used orally and intramuscularly in multiple divided doses, clinically for the management arthritis, cancer pain, post-surgical pain, and in the treatment of migraine pain. KTM has short biological half-life of 4 to 6 hours, which necessitates frequent dosing to retain the action. The frequent occurrence of gastrointestinal bleeding, perforation, peptic ulceration, and renal failure lead to the development of other drug delivery strategies for the appropriate delivery of KTM. The ideal solution would be to target the drug only to the cells or tissues affected by the disease. Drug targeting could be achieved effectively by liposomes that are biocompatible and biodegradable. The aim of the study was to develop a parenteral liposome formulation of KTM with improved efficacy while reducing side effects by targeting the inflammation due to arthritis. PEG-anchored (stealth) and non-PEG-anchored liposomes were prepared by thin film hydration technique followed by extrusion cycle and characterized for in vitro and in vivo. Stealth liposomes (SLs) exhibited increase in percent encapsulation efficiency (94%) and 52% percent of drug retention during release studies in 24 h with good stability for a period of 1 month at -20°C and 4°C. SLs showed about maximum 55% of edema inhibition with significant analgesic effect. SLs produced marked differences over those of non-SL formulations with an increase in area under plasma concentration time curve, t₁/₂, mean residence time, and reduced clearance. 0.3% of the drug was detected in arthritic induced paw with significantly reduced drug localization in liver, spleen, and kidney for SLs when compared to other conventional liposomes. Thus SLs help to increase the therapeutic efficacy of KTM by increasing the targeting potential at the inflammatory region.

Keywords: biodistribution, ketorolac tromethamine, stealth liposomes, thin film hydration technique

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79 Determination of Cyclic Citrullinated Peptide Antibodies on Quartz Crystal Microbalance Based Nanosensors

Authors: Y. Saylan, F. Yılmaz, A. Denizli

Abstract:

Rheumatoid arthritis (RA) which is the most common autoimmune disorder of the body's own immune system attacking healthy cells. RA has both articular and systemic effects.Until now romatiod factor (RF) assay is used the most commonly diagnosed RA but it is not specific. Anti-cyclic citrullinated peptide (anti-CCP) antibodies are IgG autoantibodies which recognize citrullinated peptides and offer improved specificity in early diagnosis of RA compared to RF. Anti-CCP antibodies have specificity for the diagnosis of RA from 91 to 98% and the sensitivity rate of 41-68%. Molecularly imprinted polymers (MIP) are materials that are easy to prepare, less expensive, stable have a talent for molecular recognition and also can be manufactured in large quantities with good reproducibility. Molecular recognition-based adsorption techniques have received much attention in several fields because of their high selectivity for target molecules. Quartz crystal microbalance (QCM) is an effective, simple, inexpensive approach mass changes that can be converted into an electrical signal. The applications for specific determination of chemical substances or biomolecules, crystal electrodes, cover by the thin films for bind or adsorption of molecules. In this study, we have focused our attention on combining of molecular imprinting into nanofilms and QCM nanosensor approaches and producing QCM nanosensor for anti-CCP, chosen as a model protein, using anti-CCP imprinted nanofilms. For this aim, anti-CCP imprinted QCM nanosensor was characterized by Fourier transform infrared spectroscopy, atomic force microscopy, contact angle measurements and ellipsometry. The non-imprinted nanosensor was also prepared to evaluate the selectivity of the imprinted nanosensor. Anti-CCP imprinted QCM nanosensor was tested for real-time detection of anti-CCP from aqueous solution. The kinetic and affinity studies were determined by using anti-CCP solutions with different concentrations. The responses related with mass shifts (Δm) and frequency shifts (Δf) were used to evaluate adsorption properties and to calculate binding (Ka) and dissociation (Kd) constants. To show the selectivity of the anti-CCP imprinted QCM nanosensor, competitive adsorption of anti-CCP and IgM was investigated.The results indicate that anti-CCP imprinted QCM nanosensor has a higher adsorption capabilities for anti-CCP than for IgM, due to selective cavities in the polymer structure.

Keywords: anti-CCP, molecular imprinting, nanosensor, rheumatoid arthritis, QCM

Procedia PDF Downloads 336
78 Revision of Arthroplasty in Rheumatoid and Osteoarthritis: Methotrexate and Radiographic Lucency in RA Patients

Authors: Mike T. Wei, Douglas N. Mintz, Lisa A. Mandl, Arielle W. Fein, Jayme C. Burket, Yuo-Yu Lee, Wei-Ti Huang, Vivian P. Bykerk, Mark P. Figgie, Edward F. Di Carlo, Bruce N. Cronstein, Susan M. Goodman

Abstract:

Background/Purpose: Rheumatoid arthritis (RA) patients have excellent total hip arthroplasty (THA) survival, and methotrexate (MTX), an anti-inflammatory disease modifying drug which may affect bone reabsorption, may play a role. The purpose of this study is to determine the diagnosis leading to revision THA (rTHA) in RA patients and to assess the association of radiographic lucency with MTX use. Methods: All patients with validated diagnosis of RA in the institution’s THA registry undergoing rTHA from May 2007 - February 2011 were eligible. Diagnosis leading to rTHA and medication use was determined by chart review. Osteolysis was evaluated on available radiographs by measuring maximum lucency in each Gruen zone. Differences within RA patients with/without MTX in osteolysis, demographics, and medications were assessed with chi-squared, Fisher's exact tests or Mann-Whitney U tests as appropriate. The error rate for multiple comparisons of lucency in the different Gruen zones was corrected via false discovery rate methods. A secondary analysis was performed to determine differences in diagnoses leading to revision between RA and matched OA controls (2:1 match by sex age +/- 5 years). OA exclusion criteria included presence of rheumatic diseases, use of MTX, and lack of records. Results: 51 RA rTHA were identified and compared with 103 OA. Mean age for RA was 57.7 v 59.4 years for OA (p = 0.240). 82.4% RA were female v 83.5% OA (p = 0.859). RA had lower BMI than OA (25.5 v 28.2; p = 0.166). There was no difference in diagnosis leading to rTHA, including infection (RA 3.9 v OA 6.8%; p = 0.719) or dislocation (RA 23.5 v OA 23.3%; p = 0.975). There was no significant difference in the length of time the implant was in before revision: RA 11.0 v OA 8.8 years (p = 0.060). Among RA with/without MTX, there was no difference in use of biologics (30.0 v 43.3%, p = 0.283), steroids (47.6 v 50.0%, p = 0.867) or bisphosphonates (23.8 v 33.3%, p = 0.543). There was no difference in rTHA diagnosis with/without MTX, including loosening (52.4 v 56.7%, p = 0.762). There was no significant difference in lucencies with MTX use in any Gruen zone. Patients with MTX had femoral stem subsidence of 3.7mm v no subsidence without MTX (p = 0.006). Conclusion: There was no difference in the diagnosis leading to rTHR in RA and OA, although RA trended longer prior to rTHA. In this small retrospective study, there were no significant differences associated with MTX exposure or radiographic lucency among RA patients. The significance of subsidence is not clear. Further study of arthroplasty survival in RA patients is warranted.

Keywords: hip arthroplasty, methotrexate, revision arthroplasty, rheumatoid arthritis

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77 Development of 90y-Chitosan Complex for Radiosynovectomy

Authors: A. Mirzaei, S. Zolghadri, M. Athari-Allaf, H. Yousefnia, A. R. Jalilian

Abstract:

Rheumatoid arthritis is the most common autoimmune disease, leading to the destruction of the joints. The aim of this study was the preparation of 90Y-chitosan complex as a novel agent for radiosynovectomy. The complex was prepared in the diluted acetic acid solution. At the optimized condition, the radiochemical purity of higher than 99% was obtained by ITLC method on Whatman No. 1 and by using a mixture of methanol/water/acetic acid (4:4:2) as the mobile phase. The complex was stable in acidic media (pH=3) and its radiochemical purity was above 98% even after 48 hours. The biodistribution data in rats showed that there was no significant leakage of the injected activity even after 48 h. Considering all of the excellent features of the complex, 90Y-chitosan can be used to manipulate synovial inflammation effectively.

Keywords: chitosan, Y-90, radiosynovectomy, biodistribution

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76 Glycosaminoglycan, a Cartilage Erosion Marker in Synovial Fluid of Osteoarthritis Patients Strongly Correlates with WOMAC Function Subscale

Authors: Priya Kulkarni, Soumya Koppikar, Narendrakumar Wagh, Dhanshri Ingle, Onkar Lande, Abhay Harsulkar

Abstract:

Cartilage is an extracellular matrix composed of aggrecan, which imparts it with a great tensile strength, stiffness and resilience. Disruption in cartilage metabolism leading to progressive degeneration is a characteristic feature of Osteoarthritis (OA). The process involves enzymatic depolymerisation of cartilage specific proteoglycan, releasing free glycosaminoglycan (GAG). This released GAG in synovial fluid (SF) of knee joint serves as a direct measure of cartilage loss, however, limited due to its invasive nature. Western Ontario and McMaster Universities Arthritis Index (WOMAC) is widely used for assessing pain, stiffness and physical-functions in OA patients. The scale is comprised of three subscales namely, pain, stiffness and physical-function, intends to measure patient’s perspective of disease severity as well as efficacy of prescribed treatment. Twenty SF samples obtained from OA patients were analysed for their GAG values in SF using DMMB based assay. LK 1.0 vernacular version was used to attain WOMAC scale. The results were evaluated using SAS University software (Edition 1.0) for statistical significance. All OA patients revealed higher GAG values compared to the control value of 78.4±30.1µg/ml (obtained from our non-OA patients). Average WOMAC calculated was 51.3 while pain, stiffness and function estimated were 9.7, 3.9 and 37.7, respectively. Interestingly, a strong statistical correlation was established between WOMAC function subscale and GAG (p = 0.0102). This subscale is based on day-to-day activities like stair-use, bending, walking, getting in/out of car, rising from bed. However, pain and stiffness subscale did not show correlation with any of the studied markers and endorsed the atypical inflammation in OA pathology. On one side, where knee pain showed poor correlation with GAG, it is often noted that radiography is insensitive to cartilage degenerative changes; thus OA remains undiagnosed for long. Moreover, active cartilage degradation phase remains elusive to both, patient and clinician. Through analysis of large number of OA patients we have established a close association of Kellgren-Lawrence grades and increased cartilage loss. A direct attempt to correlate WOMAC and radiographic progression of OA with various biomarkers has not been attempted so far. We found a good correlation in GAG levels in SF and the function subscale.

Keywords: cartilage, Glycosaminoglycan, synovial fluid, western ontario and McMaster Universities Arthritis Index

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75 Procedure to Use Quantitative Bone-Specific SPECT/CT in North Karelia Central Hospital

Authors: L. Korpinen, P. Taskinen, P. Rautio

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This study aimed to describe procedures that we developed to use in the quantitative, bone-specific SPECT/CT at our hospital. Our procedures included the following questions for choosing imaging protocols, which were based on a clinical doctor's referral: (1) Is she/he a cancer patient or not? (2) Are there any indications of inflammatory rheumatoid arthritis? We performed about 1,106 skeletal scintigraphies over two years. About 394 patients were studied with quantitative bone-specific single-photon emission computed tomography/computerized tomography (SPECT/CT) (i.e., about 36% of all bone scintigraphies). Approximately 64% of the patients were studied using the conventional Anterior-Posterior/Posterior-Anterior imaging. Our procedure has improved efficiency and decreased cycle times.

Keywords: skeletal scintigraphy, SPECT/CT, imaging, procedure

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74 Factors Affecting General Practitioners’ Transfer of Specialized Self-Care Knowledge to Patients

Authors: Weidong Xia, Malgorzata Kolotylo, Xuan Tan

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This study examines the key factors that influence general practitioners’ learning and transfer of specialized arthritis knowledge and self-care techniques to patients during normal patient visits. Drawing on the theory of planed behavior and using matched survey data collected from general practitioners before and after training sessions provided by specialized orthopedic physicians, the study suggests that the general practitioner’s intention to use and transfer learned knowledge was influenced mainly by intrinsic motivation, organizational learning culture and absorptive capacity, but was not influenced by extrinsic motivation. The results provide both theoretical and practical implications.

Keywords: empirical study, healthcare knowledge management, patient self-care, physician knowledge transfer

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73 TNF-Kinoid® in Autoimmune Diseases

Authors: Yahia Massinissa, Melakhessou Med Akram, Mezahdia Mehdi, Marref Salah Eddine

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Cytokines are natural proteins which act as true intercellular communication signals in immune and inflammatory responses. Reverse signaling pathways that activate cytokines help to regulate different functions at the target cell, causing its activation, its proliferation, the differentiation, its survival or death. It was shown that malfunctioning of the cytokine regulation, particularly over-expression, contributes to the onset and development of certain serious diseases such as chronic rheumatoid arthritis, Crohn's disease, psoriasis, lupus. The action mode of Kinoid® technology is based on the principle vaccine: The patient's immune system is activated so that it neutralizes itself and the factor responsible for the disease. When applied specifically to autoimmune diseases, therapeutic vaccination allows the body to neutralize cytokines (proteins) overproduced through a highly targeted stimulation of the immune system.

Keywords: cytokines, Kinoid tech, auto-immune diseases, vaccination

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72 Hybrid versus Cemented Fixation in Total Knee Arthroplasty: Mid-Term Follow-Up

Authors: Pedro Gomes, Luís Sá Castelo, António Lopes, Marta Maio, Pedro Mota, Adélia Avelar, António Marques Dias

Abstract:

Introduction: Total Knee Arthroplasty (TKA) has contributed to improvement of patient`s quality of life, although it has been associated with some complications including component loosening and polyethylene wear. To prevent these complications various fixation techniques have been employed. Hybrid TKA with cemented tibial and cementless femoral components have shown favourable outcomes, although it still lack of consensus in the literature. Objectives: To evaluate the clinical and radiographic results of hybrid versus cemented TKA with an average 5 years follow-up and analyse the survival rates. Methods: A retrospective study of 125 TKAs performed in 92 patients at our institution, between 2006 to 2008, with a minimum follow-up of 2 years. The same prosthesis was used in all knees. Hybrid TKA fixation was performed in 96 knees, with a mean follow-up of 4,8±1,7 years (range, 2–8,3 years) and 29 TKAs received fully cemented fixation with a mean follow-up of 4,9±1,9 years (range, 2-8,3 years). Selection for hybrid fixation was nonrandomized and based on femoral component fit. The Oxford Knee Score (OKS 0-48) was evaluated for clinical assessment and Knee Society Roentgenographic Evaluation Scoring System was used for radiographic outcome. The survival rate was calculated using the Kaplan-Meier method, with failures defined as revision of either the tibial or femoral component for aseptic failures and all-causes (aseptic and infection). Analysis of survivorship data was performed using the log-rank test. SPSS (v22) was the computer program used for statistical analysis. Results: The hybrid group consisted of 72 females (75%) and 24 males (25%), with mean age 64±7 years (range, 50-78 years). The preoperative diagnosis was osteoarthritis (OA) in 94 knees (98%), rheumatoid arthritis (RA) in 1 knee (1%) and Posttraumatic arthritis (PTA) in 1 Knee (1%). The fully cemented group consisted of 23 females (79%) and 6 males (21%), with mean age 65±7 years (range, 47-78 years). The preoperative diagnosis was OA in 27 knees (93%), PTA in 2 knees (7%). The Oxford Knee Scores were similar between the 2 groups (hybrid 40,3±2,8 versus cemented 40,2±3). The percentage of radiolucencies seen on the femoral side was slightly higher in the cemented group 20,7% than the hybrid group 11,5% p0.223. In the cemented group there were significantly more Zone 4 radiolucencies compared to the hybrid group (13,8% versus 2,1% p0,026). Revisions for all causes were performed in 4 of the 96 hybrid TKAs (4,2%) and 1 of the 29 cemented TKAs (3,5%). The reason for revision was aseptic loosening in 3 hybrid TKAs and 1 of the cemented TKAs. Revision was performed for infection in 1 hybrid TKA. The hybrid group demonstrated a 7 years survival rate of 93% for all-cause failures and 94% for aseptic loosening. No significant difference in survivorship was seen between the groups for all-cause failures or aseptic failures. Conclusions: Hybrid TKA yields similar intermediate-term results and survival rates as fully cemented total knee arthroplasty and remains a viable option in knee joint replacement surgery.

Keywords: hybrid, survival rate, total knee arthroplasty, orthopaedic surgery

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71 Evaluation of Computer Usage and Related Health Hazards

Authors: B. O. Adegoke, B. O. Ola, D. T. Ademiluyi

Abstract:

This paper examines the use of computer and its related health hazard among computer users in South-Western zone of Nigeria. Two hundred and eighteen (218) computer users constituted the population used to evaluate association between posture, extensive computer use and related health hazard. The instruments for the study are a questionnaire on demographics, lifestyle, body features and work ability index while mean rating, standard deviation and t test were used for data analysis. Identified health related hazard include damages to the eyesight, bad posture, arthritis, musculoskeletal disorders, headache, stress and so on. The results showed that factors such as work demand, posture, closeness to computer screen and excessive working hours on computers constitute health hazards in both old and young computer users of various gender. It is therefore recommended that total number of hours spent with computer should be monitored and controlled.

Keywords: computer-related health hazard, musculoskeletal disorders, computer usage, work ability index

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70 Static and Dynamic Load on Hip Contact of Hip Prosthesis and Thai Femoral Bones

Authors: K. Chalernpon, P. Aroonjarattham, K. Aroonjarattham

Abstract:

Total hip replacement had been one of the most successful operations in hip arthritis surgery. The purpose of this research had been to develop a dynamic hip contact of Thai femoral bone to analyze the stress distribution on the implant and the strain distribution on the bone model under daily activities and compared with the static load simulation. The results showed the different of maximum von Mises stress 0.14 percent under walking and 0.03 percent under climbing stair condition and the different of equivalent total strain 0.52 percent under walking and 0.05 percent under climbing stair condition. The muscular forces should be evaluated with dynamic condition to reduce the maximum von Mises stress and equivalent total strain.

Keywords: dynamic loading, static load, hip prosthesis, Thai femur, femoral bone, finite element analysis

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69 Effects of Dietary Factors on Gout

Authors: Olor Obi, Ishiekwen Bridget, Ekpeyong Edom

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Even though gout is becoming more common, the role of dietary risk factors in the development and management of this condition remains unclear. Therefore, this review work will aim at clarifying the role of dietary factors in the risk and management of gout. An extensive search of literature published between 1960 and 2018 will be performed on the databases of PubMed, CINAHL, Science Direct, Cochrane, BMJ, Ann Rheum Dis, and BioMed to identify relevant cohort, prospective, population-based, or cross-sectional studies that examined the effect of diet on gout. About 19 studies will be included in this review work. The methodological quality of these studies will be evaluated using the quality assessment tool for observational and cross-sectional studies developed by the National Heart, Lungs, and Blood Institute. This work intends to reveal that a positive association exists between the intake of sugary, sweetened beverages and the risk of gout. It will also reveal the relationship between the increase in coffee consumption and the risk of gout.

Keywords: gout, dietary factors, management of gout, gouty arthritis

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68 PolyScan: Comprehending Human Polymicrobial Infections for Vector-Borne Disease Diagnostic Purposes

Authors: Kunal Garg, Louise Theusen Hermansan, Kanoktip Puttaraska, Oliver Hendricks, Heidi Pirttinen, Leona Gilbert

Abstract:

The Germ Theory (one infectious determinant is equal to one disease) has unarguably evolved our capability to diagnose and treat infectious diseases over the years. Nevertheless, the advent of technology, climate change, and volatile human behavior has brought about drastic changes in our environment, leading us to question the relevance of the Germ Theory in our day, i.e. will vector-borne disease (VBD) sufferers produce multiple immune responses when tested for multiple microbes? Vector diseased patients producing multiple immune responses to different microbes would evidently suggest human polymicrobial infections (HPI). Ongoing diagnostic tools are exceedingly unequipped with the current research findings that would aid in diagnosing patients for polymicrobial infections. This shortcoming has caused misdiagnosis at very high rates, consequently diminishing the patient’s quality of life due to inadequate treatment. Equipped with the state-of-art scientific knowledge, PolyScan intends to address the pitfalls in current VBD diagnostics. PolyScan is a multiplex and multifunctional enzyme linked Immunosorbent assay (ELISA) platform that can test for numerous VBD microbes and allow simultaneous screening for multiple types of antibodies. To validate PolyScan, Lyme Borreliosis (LB) and spondyloarthritis (SpA) patient groups (n = 54 each) were tested for Borrelia burgdorferi, Borrelia burgdorferi Round Body (RB), Borrelia afzelii, Borrelia garinii, and Ehrlichia chaffeensis against IgM and IgG antibodies. LB serum samples were obtained from Germany and SpA serum samples were obtained from Denmark under relevant ethical approvals. The SpA group represented chronic LB stage because reactive arthritis (SpA subtype) in the form of Lyme arthritis links to LB. It was hypothesized that patients from both the groups will produce multiple immune responses that as a consequence would evidently suggest HPI. It was also hypothesized that the multiple immune response proportion in SpA patient group would be significantly larger when compared to the LB patient group across both antibodies. It was observed that 26% LB patients and 57% SpA patients produced multiple immune responses in contrast to 33% LB patients and 30% SpA patients that produced solitary immune responses when tested against IgM. Similarly, 52% LB patients and an astounding 73% SpA patients produced multiple immune responses in contrast to 30% LB patients and 8% SpA patients that produced solitary immune responses when tested against IgG. Interestingly, IgM immune dysfunction in both the patient groups was also recorded. Atypically, 6% of the unresponsive 18% LB with IgG antibody was recorded producing multiple immune responses with the IgM antibody. Similarly, 12% of the unresponsive 19% SpA with IgG antibody was recorded producing multiple immune responses with the IgM antibody. Thus, results not only supported hypothesis but also suggested that IgM may atypically prevail longer than IgG. The PolyScan concept will aid clinicians to detect patients for early, persistent, late, polymicrobial, & immune dysfunction conditions linked to different VBD. PolyScan provides a paradigm shift for the VBD diagnostic industry to follow that will drastically shorten patient’s time to receive adequate treatment.

Keywords: diagnostics, immune dysfunction, polymicrobial, TICK-TAG

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67 ANA Negative but FANA Positive Patients with Clinical Symptoms of Rheumatic Disease: The Suggestion for Clinicians

Authors: Abdolreza Esmaeilzadeh, Mehri Mirzaei

Abstract:

Objective: Rheumatic disease is a chronic disease that causes pain, stiffness, swelling and limited motion and function of many joints. RA is the most common form of autoimmune arthritis, affecting more than 1.3 million Americans. Of these, about 75% are women. Materials and Methods: This study was formed due to the misconception about ANA test, which is frequently performed with methods based upon solid phase as ELISA. This experiment was conducted on 430 patients, with clinical symptoms that are likely affected with rheumatic diseases, simultaneously by means of ANA and FANA. Results: 36 cases (8.37%) of patients, despite positive ANA, have demonstrated negative results via Indirect Immunofluorescence Assay (IIFA), (false positive). 116 cases (27%) have demonstrated negative ANA results, by means of the ELISA technique, although they had positive IIFA results. Conclusion: Other advantages of IIFA are antibody titration and specific pattern detection that have the capability of distinguishing positive dsDNA results. According to the restrictions and false negative cases, in patients, IIFA test is highly recommended for these disease's diagnosis.

Keywords: autoimmune disease, IIFA, EIA, rheumatic disease

Procedia PDF Downloads 475
66 The Impact of Technology on Computer Systems and Technology

Authors: Bishoy Abouelsoud Saad Amin

Abstract:

This paper examines the use of computer and its related health hazard among computer users in South-Western zone of Nigeria. Two hundred and eighteen (218) computer users constituted the population used to evaluate association between posture, extensive computer use and related health hazard. The instruments for the study are a questionnaire on demographics, lifestyle, body features and work ability index while mean rating, standard deviation and t test were used for data analysis. Identified health related hazard include damages to the eyesight, bad posture, arthritis, musculoskeletal disorders, headache, stress and so on. The results showed that factors such as work demand, posture, closeness to computer screen and excessive working hours on computers constitute health hazards in both old and young computer users of various gender. It is therefore recommended that total number of hours spent with computer should be monitored and controlled.

Keywords: computer game, metaphor, middle school students, virtual environments computer auditing, risk, measures to prevent, information management computer-related health hazard, musculoskeletal disorders, computer usage, work ability index

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65 Self-Regenerating, Vascularizing Hybrid Scaffold-Hydrogel For Bone Tissue Engineering

Authors: Alisha Gupta

Abstract:

Osteoarthritis (OA) is the most common form of arthritis which is a degenerative joint disease causing joints to begin to break down and underlying bones to change. This “wear and tear” most frequently affects hands, hips, and knees. This is important because OA pain is considered to be a leading cause of mobility impairment in older adults, with hip and knee OA ranked 11th highest contributors to global disability. Bone tissue engineering utilizing polymer scaffolds and hydrogels is an emerging field for treating osteoarthritis. Polymer scaffolds provide a three-dimensional structure for tissue growth, and hydrogels can be used to deliver drugs and growth factors. The combination of the two materials creates a hybrid structure that can better withstand physiological and mechanical demands while also providing a more controlled environment for drug and nutrient delivery. I think using bone tissue engineering for making scaffold-hydrogel composites that are self-regenerating and vascularizing might be useful in solving this problem. Successful implementation can reconstruct healthy, simulated bone tissue on deficient applicants.

Keywords: tissue engineering, regenerative medicine, scaffold-hydrogel composites, osteoarthritis

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64 Pulsatile Drug Delivery System for Chronopharmacological Disorders

Authors: S. S. Patil, B. U. Janugade, S. V. Patil

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Pulsatile systems are gaining a lot of interest as they deliver the drug at the right site of action at the right time and in the right amount, thus providing spatial and temporal delivery thus increasing patient compliance. These systems are designed according to the circadian rhythm of the body. Chronotherapeutics is the discipline concerned with the delivery of drugs according to inherent activities of a disease over a certain period of time. It is becoming increasingly more evident that the specific time that patients take their medication may be even more significant than was recognized in the past. The tradition of prescribing medication at evenly spaced time intervals throughout the day, in an attempt to maintain constant drug levels throughout a 24-hour period, may be changing as researcher’s report that some medications may work better if their administration is coordinated with day-night patterns and biological rhythms. The potential benefits of chronotherapeutics have been demonstrated in the management of a number of diseases. In particular, there is a great deal of interest in how chronotherapy can particularly benefit patients suffering from allergic rhinitis, rheumatoid arthritis and related disorders, asthma, cancer, cardiovascular diseases, and peptic ulcer disease.

Keywords: pulsatile drug delivery, chronotherapeutics, circadian rhythm, asthma, chronobiology

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63 Glycyrrhizic Acid Inhibits Lipopolysaccharide-Stimulated Bovine Fibroblast-Like Synoviocyte, Invasion through Suppression of TLR4/NF-κB-Mediated Matrix Metalloproteinase-9 Expression

Authors: Hosein Maghsoudi

Abstract:

Rheumatois arthritis (RA) is progressive inflammatory autoimmune diseases that primarily affect the joints, characterized by synovial hyperplasia and inflammatory cell infiltration, deformed and painful joints, which can lead tissue destruction, functional disability systemic complications, and early dead and socioeconomic costs. The cause of rheumatoid arthritis is unknown, but genetic and environmental factors are contributory and the prognosis is guarded. However, advances in understanding the pathogenesis of the disease have fostered the development of new therapeutics, with improved outcomes. The current treatment strategy, which reflects this progress, is to initiate aggressive therapy soon after diagnosis and to escalate the therapy, guided by an assessment of disease activity, in pursuit of clinical remission. The pathobiology of RA is multifaceted and involves T cells, B cells, fibroblast-like synoviocyte (FLSc) and the complex interaction of many pro-inflammatory cytokine. Novel biologic agents that target tumor necrosis or interlukin (IL)-1 and Il-6, in addition T- and B-cells inhibitors, have resulted in favorable clinical outcomes in patients with RA. Despite this, at least 30% of RA patients are résistance to available therapies, suggesting novel mediators should be identified that can target other disease-specific pathway or cell lineage. Among the inflammatory cell population that might participated in RA pathogenesis, FLSc are crucial in initiaing and driving RA in concert of cartilage and bone by secreting metalloproteinase (MMPs) into the synovial fluid and by direct invasion into extracellular matrix (ECM), further exacerbating joint damage. Invasion of fibroblast-like synoviocytes (FLSc) is critical in the pathogenesis of rheumatoid-arthritis. The metalloproteinase (MMPs) and activator of Toll-like receptor 4 (TLR4)/nuclear factor- κB pthway play a critical role in RA-FLS invasion induced by lipopolysaccharide (LPS). The present study aimed to explore the anti-invasion activity of Glycyrrhizic Acid as a pharmacologically safe phytochemical agent with potent anti-inflammatory properties on IL-1beta and TNF-alpha signalling pathways in Bovine fibroblast-like synoviocyte ex- vitro, on LPS-stimulated bovine FLS migration and invasion as well as MMP expression and explored the upstream signal transduction. Results showed that Glycyrrhizic Acid suppressed LPS-stimulated bovine FLS migration and invasion by inhibition MMP-9 expression and activity. In addition our results revealed that Glycyrrhizic Acid inhibited the transcriptional activity of MMP-9 by suppression the nbinding activity of NF- κB in the MMP-9 promoter pathway. The extract of licorice (Glycyrrhiza glabra L.) has been widely used for many centuries in the traditional Chinese medicine as native anti-allergic agent. Glycyrrhizin (GL), a triterpenoidsaponin, extracted from the roots of licorice is the most effective compound for inflammation and allergic diseases in human body. The biological and pharmacological studies revealed that GL possesses many pharmacological effects, such as anti-inflammatory, anti-viral and liver protective effects, and the biological effects, such as induction of cytokines (interferon-γ and IL-12), chemokines as well as extrathymic T and anti-type 2 T cells. GL is known in the traditional Chinese medicine for its anti-inflammatory effect, which is originally described by Finney in 1959. The mechanism of the GL-induced anti-inflammatory effect is based on different pathways of the GL-induced selective inhibition of the prostaglandin E2 production, the CK-II- mediated activation of both GL-binding lipoxygenas (gbLOX; 17) and PLA2, an anti-thrombin action of GL and production of the reactive oxygen species (ROS; GL exerts liver protection properties by inhibiting PLA2 or by the hydroxyl radical trapping action, leading to the lowering of serum alanine and aspartate transaminase levels. The present study was undertaken to examine the possible mechanism of anti-inflammatory properties GL on IL-1beta and TNF-alpha signalling pathways in bovine fibroblast-like synoviocyte ex-vivo, on LPS-stimulated bovine FLS migration and invasion as well as MMP expression and explored the upstream signal transduction. Our results clearly showed that treatment of bovine fibroblast-like synoviocyte with GL suppressed LPS-induced cell migration and invasion. Furthermore, it revealed that GL inhibited the transcription activity of MMP-9 by suppressing the binding activity of NF-κB in the MM-9 promoter. MMP-9 is an important ECM-degrading enzyme and overexpression of MMPs in important of RA-FLSs. LPS can stimulate bovine FLS to secret MMPs, and this induction is regulated at the transcription and translational levels. In this study, LPS treatment of bovine FLS caused an increase in MMP-2 and MMP-9 levels. The increase in MMP-9 expression and secretion was inhibited by ex- vitro. Furthermore, these effects were mimicked by MMP-9 siRNA. These result therefore indicate the the inhibition of LPS-induced bovine FLS invasion by GL occurs primarily by inhibiting MMP-9 expression and activity. Next we analyzed the functional significance of NF-κB transcription of MMP-9 activation in Bovine FLSs. Results from EMSA showed that GL suppressed LPS-induced NF-κB binding to the MMP-9 promotor, as NF-κB regulates transcriptional activation of multiple inflammatory cytokines, we predicted that GL might target NF-κB to suppress MMP-9 transcription by LPS. Myeloid differentiation-factor 88 (MyD88) and TIR-domain containing adaptor protein (TIRAP) are critical proteins in the LPS-induced NF-κB and apoptotic signaling pathways, GL inhibited the expression of TLR4 and MYD88. These results demonstrated that GL suppress LPS-induced MMP-9 expression through the inhibition of the induced TLR4/NFκB signaling pathway. Taken together, our results provide evidence that GL exerts anti-inflammatory effects by inhibition LPS-induced bovine FLSs migration and invasion, and the mechanisms may involve the suppression of TLR4/NFκB –mediated MMP-9 expression. Although further work is needed to clarify the complicated mechanism of GL-induced anti-invasion of bovine FLSs, GL might be used as a further anti-invasion drug with therapeutic efficacy in the treatment of immune-mediated inflammatory disease such as RA.

Keywords: glycyrrhizic acid, bovine fibroblast-like synoviocyte, tlr4/nf-κb, metalloproteinase-9

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62 Methotrexate Associated Skin Cancer: A Signal Review of Pharmacovigilance Center

Authors: Abdulaziz Alakeel, Abdulrahman Alomair, Mohammed Fouda

Abstract:

Introduction: Methotrexate (MTX) is an antimetabolite used to treat multiple conditions, including neoplastic diseases, severe psoriasis, and rheumatoid arthritis. Skin cancer is the out-of-control growth of abnormal cells in the epidermis, the outermost skin layer, caused by unrepaired DNA damage that triggers mutations. These mutations lead the skin cells to multiply rapidly and form malignant tumors. The aim of this review is to evaluate the risk of skin cancer associated with the use of methotrexate and to suggest regulatory recommendations if required. Methodology: Signal Detection team at Saudi Food and Drug Authority (SFDA) performed a safety review using National Pharmacovigilance Center (NPC) database as well as the World Health Organization (WHO) VigiBase, alongside with literature screening to retrieve related information for assessing the causality between skin cancer and methotrexate. The search conducted in July 2020. Results: Four published articles support the association seen while searching in literature, a recent randomized control trial published in 2020 revealed a statistically significant increase in skin cancer among MTX users. Another study mentioned methotrexate increases the risk of non-melanoma skin cancer when used in combination with immunosuppressant and biologic agents. In addition, the incidence of melanoma for methotrexate users was 3-fold more than the general population in a cohort study of rheumatoid arthritis patients. The last article estimated the risk of cutaneous malignant melanoma (CMM) in a cohort study shows a statistically significant risk increase for CMM was observed in MTX exposed patients. The WHO database (VigiBase) searched for individual case safety reports (ICSRs) reported for “Skin Cancer” and 'Methotrexate' use, which yielded 121 ICSRs. The initial review revealed that 106 cases are insufficiently documented for proper medical assessment. However, the remaining fifteen cases have extensively evaluated by applying the WHO criteria of causality assessment. As a result, 30 percent of the cases showed that MTX could possibly cause skin cancer; five cases provide unlikely association and five un-assessable cases due to lack of information. The Saudi NPC database searched to retrieve any reported cases for the combined terms methotrexate/skin cancer; however, no local cases reported up to date. The data mining of the observed and the expected reporting rate for drug/adverse drug reaction pair is estimated using information component (IC), a tool developed by the WHO Uppsala Monitoring Centre to measure the reporting ratio. Positive IC reflects higher statistical association, while negative values translated as a less statistical association, considering the null value equal to zero. Results showed that a combination of 'Methotrexate' and 'Skin cancer' observed more than expected when compared to other medications in the WHO database (IC value is 1.2). Conclusion: The weighted cumulative pieces of evidence identified from global cases, data mining, and published literature are sufficient to support a causal association between the risk of skin cancer and methotrexate. Therefore, health care professionals should be aware of this possible risk and may consider monitoring any signs or symptoms of skin cancer in patients treated with methotrexate.

Keywords: methotrexate, skin cancer, signal detection, pharmacovigilance

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61 Application of Coaxial Electrospinning for the Encapsulation of Omega-3 Fatty Acids

Authors: Sokratis Koskinakis, Georgia Frakolaki, Magdalini Krokida

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Regular consumption of omega-3 fatty acid-rich lipids is said to provide a wide range of health benefits, including prevention of inflammation, cardiovascular disease, diabetes, arthritis, and ulcerative colitis. Because of their potential nutritional and health benefits, the omega-3 PUFAs are increasingly being supplemented in functional food products meant to improve human health and wellbeing. However, dietary fortification with PUFAs is difficult due to their low water solubility, tendency to oxidize quickly, and inconsistent bioavailability. These issues can be solved through application of modern encapsulation technologies, which typically entail integrating omega-3 oils into well-designed matrices made from food-grade components. Electrospinning, for example, is an effective encapsulation method for producing sub-micron or nano-scale polymer fibers. For this purpose, various combinations of hydroxypropyl-β-cyclodextrin and cellulose nanocrystals/ nanofibers were assessed for the encapsulation of omega-3 fatty acids through the innovative technology of electrospinning. The encapsulation yield was evaluated through GC-analysis, and the morphology of the final products was assessed through SEM analysis.

Keywords: electrospinning, encapsulation, omega-3 fatty acids, cellulose nanocrystals / nanofibers

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60 A Dynamic Model for Assessing the Advanced Glycation End Product Formation in Diabetes

Authors: Victor Arokia Doss, Kuberapandian Dharaniyambigai, K. Julia Rose Mary

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Advanced Glycation End (AGE) products are the end products due to the reaction between excess reducing sugar present in diabetes and free amino group in protein lipids and nucleic acids. Thus, non-enzymic glycation of molecules such as hemoglobin, collagen, and other structurally and functionally important proteins add to the pathogenic complications such as diabetic retinopathy, neuropathy, nephropathy, vascular changes, atherosclerosis, Alzheimer's disease, rheumatoid arthritis, and chronic heart failure. The most common non-cross linking AGE, carboxymethyl lysine (CML) is formed by the oxidative breakdown of fructosyllysine, which is a product of glucose and lysine. CML is formed in a wide variety of tissues and is an index to assess the extent of glycoxidative damage. Thus we have constructed a mathematical and computational model that predicts the effect of temperature differences in vivo, on the formation of CML, which is now being considered as an important intracellular milieu. This hybrid model that had been tested for its parameter fitting and its sensitivity with available experimental data paves the way for designing novel laboratory experiments that would throw more light on the pathological formation of AGE adducts and in the pathophysiology of diabetic complications.

Keywords: advanced glycation end-products, CML, mathematical model, computational model

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59 Aristotle University of Thessaloniki

Authors: Ail Akbar Emamverdian, Neriman Özada, Atabak Rahimzadeh Ilkhchi, Zahra Emamverdian

Abstract:

The reverse shoulder prosthesis is an innovative procedure design to treat of (GH) joint problems with severe rotator cuff deficiency. The original reverse shoulder prosthesis was invented by France surgery in1985 and has been in clinical use in the United States in 2004. These prostheses consist of baseplate that attached to the glenoid, in order to hold a spherical component, and humeral part consist of polyethylene insert which is flat. This prosthesis is the ‘reverse’ configuration. The indications for the reverse prosthesis are: (1) treating failed hemi arthroplasty with irrecoverable rotator cuff tears, (2) relief of painful arthritis associated with cuff tear arthropathy, (3) instauration after tumor resection, (4) pseudo paralysis because of irrecoverable rotator cuff tears (5) some fractures of the shoulder which reverse shoulder prostheses is only the option for treatment. This prosthesis resulting in relief of pain and decreasing the range of motion in above indications. However, this prosthesis and its applications such as notching of the scapula, dislocation of the prosthesis parts and acromial stress fractures. In this article the reverse shoulder prostheses, indication has been reviewed. This study can make clear aspect of reverse shoulder prosthesis that can help to find some solution in future.

Keywords: prostheses, complications, reverse shoulder prosthesis, indications

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58 Preparation and Characterization of Diclofenac Sodium Loaded Solid Lipid Nanoparticle

Authors: Oktavia Eka Puspita

Abstract:

The possibility of using Solid Lipid Nanoparticles (SLN) for topical use is an interesting feature concerning this system has occlusive properties on the skin surface therefore enhance the penetration of drugs through the stratum corneum by increased hydration. This advantage can be used to enhance the drug penetration of topical delivery such as Diclofenac sodium for the relief of signs and symptoms of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis. The purpose of this study was focused on the preparation and physical characterization of Diclofenac sodium loaded SLN (D-SLN). D loaded SLN were prepared by hot homogenization followed by ultrasonication technique. Since the occlusion factor of SLN is related to its particle size the formulation of D-SLN in present study two formulations different in its surfactant contents were prepared to investigate the difference of the particle size resulted. Surfactants selected for preparation of formulation A (FA) were lecithin soya and Tween 80 whereas formulation B (FB) were lecithin soya, Tween 80, and Sodium Lauryl Sulphate. D-SLN were characterized for particle size and distribution, polydispersity index (PI), zeta potential using Beckman-Coulter Delsa™ Nano. Overall, the particle size obtained from FA was larger than FB. FA has 90% of the particles were above 1000 nm, while FB has 90% were below 100 nm.

Keywords: solid lipid nanoparticles, hot homogenization technique, particle size analysis, topical administration

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57 Role of Interlukin-18 in Primary Knee Osteoarthritis: Clinical, Laboratory and Radiological Study

Authors: Ibrahim Khalil Ibrahim, Enas Mohamed Shahine, Abeer Shawky El Hadedy, Emmanuel Kamal Aziz Saba, Ghada Salah Attia Hussein

Abstract:

Osteoarthritis (OA) is a multifactorial disease characterized by a progressive degradation of articular cartilage and is the leading cause of disability in elderly persons. IL-18 contributes to the destruction of cartilage and bone in the disease process of arthritis. The aim of the study was to investigate the role of IL-18 in primary knee OA patients. Serum level of IL-18 was assessed by enzyme-linked immunosorbent assay in 30 primary knee OA patients and compared to 20 age and gender-matched healthy volunteers as a control group. Radiographic severity of OA was assessed by Kellgren and Lawrence (KL) global scale. Pain, stiffness and functional assessment were done using Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). OA patients had significantly higher serum IL-18 level than in control group (420.93 ± 345.4 versus 151.03 ± 144.16 pg/ml, P=0.001). Serum level of IL-18 was positively correlated with KL global scale (P=0.001). There were no statistically significant correlations between serum level of IL-18 and pain, stiffness, function subscales and total WOMAC index scores among the studied patients. In conclusions, IL-18 has a role in the pathogenesis of OA and it is positively correlated with the radiographic damage of OA.

Keywords: Interlukin-18, knee osteoarthritis, primary osteoarthritis, WOMAC scale

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56 Preparation and Antioxidant Activity of Heterocyclic Indole Derivatives

Authors: Tunca Gul Altuntas, Aziz Baydar, Cemre Acar, Sezen Yılmaz, Tulay Coban

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Free radicals, which are generated in many bioorganic redox processes, play a role in the pathogenesis of several diseases including cancer, arthritis, hemorrhagic shock, inflammatory, cardiovascular, neurodegenerative diseases and age-related degenerative brain diseases. Exposures of normal cell to free radical damages several structures, oxidizes nucleic acids, proteins, lipids, or DNA. Compounds interfere with the action of reactive oxygen species might be useful in prevention and treatment of these pathologies. A series of indole compounds containing piperazine ring were synthesized. Coupling of indole-2-carboxylic acid with monosubstituted piperazines was accomplished with 1,1’-carbonyldiimidazole (CDI) in a good yield. The structures of prepared compounds were verified in good agreement with their 1H NMR (nuclear magnetic resonance), MS (mass spectrophotometry), and IR (infrared spectrophotometry) characteristics. In this work, all synthetized indole derivatives were screened in vitro for their antioxidative potential against vitamin E (α-tocopherol) using different antioxidant assays such as superoxide anion formation, lipid peroxidation levels in rat liver, and 2,2-diphenyl-1-picrylhydrazyl (DPPH) stable radical scavenging activity. The synthesized compounds showed various levels of inhibition compared to vitamin E. This may give promising results for the development of new antioxidant agents.

Keywords: antioxidant, indoles, piperazines, reactive oxygen species

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55 Synthesis of a Library of Substituted Isoquinolines Based on a Triazolization Strategy, and Their Anti-HIV and C-X-C Chemokine Receptor Type 4 Antagonist Activity

Authors: Mastaneh Safarnejad Shad, Wim Dehaen, Steven De Jonghe

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Since CXCR4 is the main coreceptor of HIV-1 and plays an important role in human immunodeficiency virus (HIV) entry, numerous efforts were directed towards the discovery of new classes of small molecules that act as CXCR4 antagonists. In addition, CXCR4 antagonists are potentially useful in the treatment of several other disorders, such as cancer cell metastasis, leukemia cell proliferation, rheumatoid arthritis, and pulmonary fibrosis. Since AMD3100 (plerixafor) is the only CXCR4 antagonist which obtained approval by the Food and Drug Administration (FDA), we were motivated to investigate a new category of molecules as CXCR4 antagonists. Most of the scaffolds which have been studied so far as CXCR4 antagonists are based on the tetrahydroquinoline (THQ) moiety in which AMD11070 (mavorixafor), GSK-812394, and TIQ15 displayed the most potent CXCR4 antagonism. Due to the high potency of these scaffolds, two different series of compounds were prepared in this work. In the first set, the THQ moiety is coupled to an amine chain and various isoquinoline derivatives (prepared by an in-house developed triazolization strategy), of which the upper part of molecules is identical to AMD11070 and TIQ15. In the second category of compounds, the THQ moiety was simplified by the synthesis of a substituted pyridine moiety. In order to investigate if CXCR4 antagonism requires the presence of an isoquinoline moiety, the corresponding pyridine analogues were also prepared. In both series of compounds, potent CXCR4 antagonism was noticed.

Keywords: CXCR4 coreceptor, CXCR4 antagonists, HIV inhibitor, tetrahydroquinoline

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54 An Engineered Epidemic: Big Pharma's Role in the Opioid Crisis

Authors: Donna L. Roberts

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2019 marked 23 years since Purdue Pharma launched its flagship drug, OxyContin, that unleashed an unprecedented epidemic touching both celebrities and common citizens, metropolitan, suburbia and rural areas and all levels of socioeconomic status. From rural Appalachia to East LA individuals, families and communities have been devastated by a trajectory of addiction that often began with the legitimate prescription of a pain killer for anything from a tooth extraction to a sports injury to recovery from surgery or chronic arthritis. Far from being a serendipitous progression of events, the proliferation of this new breed of 'miracle drug' was instead a carefully crafted marketing program aimed at both the medical community and common citizens. This research represents and in-depth investigation of the evolution of the marketing, distribution and promotion of prescription opioids by pharmaceutical companies and its relationship to the propagation of the opioid crisis. Specifically, key components of Purdue Pharma’s aggressive marketing campaign, including its bonus system and sales incentives, were analyzed in the context of the sociopolitical environment that essential created the proverbial 'perfect storm' for the changing manner in which pain is treated in the U.S. The analyses of these series of events clearly indicate their role in first, the increase in prescription of opioids for non-terminal pain relief and subsequently, the incidence of related addiction, overdose, and death. Through this examination of the conditions that facilitated and maintained this drug crisis, perhaps we can begin to chart a course toward its resolution.

Keywords: addiction, opioid, opioid crisis, Purdue Pharma

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