Preparation and in vitro Characterization of Porous Carrier–Based Glipizide Floating Microspheres for Gastric Delivery

Floating microspheres have been utilized to obtain prolonged and uniform release of drug in the stomach for development of once-daily formulations. A controlled-release system designed to increase residence time in the stomach without contact with the mucosa was achieved through the preparation of floating microspheres by the emulsion solvent diffusion technique, using (i) calcium silicate (CS) as porous carrier; (ii) glipizide, an oral hypoglycemic agent; and (iii) Eudragit® S as polymer. The effects of various formulations and process variables on the internal and external particle morphology, micromeritic properties, in vitro floating behavior, drug loading, and in vitro drug release were studied. The microspheres were found to be regular in shape and highly porous. The prepared microspheres exhibited prolonged drug release (~8 h) and remained buoyant for >10 h. The mean particle size increased and the drug release rate decreased at higher polymer concentrations. No significant effect of the stirring rate during preparation on drug release was observed. In vitro studies demonstrated diffusion-controlled drug release from the microspheres. Microsphere formulation CS4, containing 200 mg calcium silicate, showed the best floating ability (88% buoyancy) in simulated gastric fluid. The release pattern of glipizide in simulated gastric fluid from all floating microspheres followed the Higuchi matrix model and the Peppas-Korsmeyer model

Dietary habits and nutrition in rheumatoid arthritis: can diet influence disease development and clinical manifestations?

Rheumatoid arthritis (RA) is a systemic, autoimmune disease characterized by joint involvement, with progressive cartilage and bone destruction. Genetic and environmental factors determine RA susceptibility. In recent years, an increasing number of studies suggested that diet has a central role in disease risk and progression. Several nutrients, such as polyunsaturated fatty acids, present anti-inflammatory and antioxidant properties, featuring a protective role for RA development, while others such as red meat and salt have a harmful effect. Gut microbiota alteration and body composition modifications are indirect mechanisms of how diet influences RA onset and progression. Possible protective effects of some dietary patterns and supplements, such as the Mediterranean Diet (MD), vitamin D and probiotics, could be a possible future adjunctive therapy to standard RA treatment. Therefore, a healthy lifestyle and nutrition have to be encouraged in patients with RA

OP0086 GENDER INFLUENCE ON CLINICAL MANIFESTATIONS, DEPRESSIVE SYMPTOMS AND BRAIN-DERIVED NEUROTROPHIC FACTOR (BDNF) SERUM LEVELS IN PATIENTS AFFECTED BY FIBROMYALGIA

Background:Fibromyalgia (FM) is a common rheumatic disease characterized by chronic widespread pain, sleep and mood disorders. A higher prevalence of FM in women compared with men is well known, although the specific differences in clinical manifestations related to gender are still poorly defined. Brain-Derived Neurotrophic Factor (BDNF) is an endogenous growth factor that gained attention for its potential as biomarker of several diseases, including FM and depression.Objectives:The aims of this study were to investigate gender-related difference among males and females affected by FM in clinical manifestations, depressive features and BDNF serum level, evaluating also the diagnostic potential of the latter.Methods:We consecutively enrolled adult patients affected by FM (ACR 2016) referring to our out-patient clinic. Each subject underwent clinical and answered to questionnaires for the severity of FM symptoms (Revised Fibromyalgia Impact Questionnaire, R-FIQ) and depressive symptoms (Beck Depression Inventory-II, BDI-II). We collected blood samples from a subgroup of patients of both sexes, matched for age, for BDNF serum level dosage through ELISA. BDNF levels were assessed also in a control group, matched for sex and age.Results:The cohort was composed by 201 FM patients (172 F, 29 M), mean age 49.13. Females showed higher values of R-FIQ total score (p=0,0005) as well the specific items of the R-FIQ for pain (p=0,013), fatigue (p=0,014), memory problems (p=0,007), tenderness to touch (p<0,0001), balance problems (p<0,0001) and sensitivity to environmental stimuli (p=0,012) when compared with males (fig. 1). There was no difference in BDI-II between males and females, but notably male patients reported a significantly higher frequency of coexisting depressive disorder (p=0,038) (fig. 2). Serum BDNF levels were evaluated in 40 FM patients and 40 healthy controls (HC) (F:M 1:1). BDNF levels were significantly lower in FM patients compared with HC (p<0,0001). Among FM patients, BDNF levels were lower in males compared with females (p<0,0001) (fig.3). BDNF did not correlate with any clinical and clinimetric parameter. BDNF showed a good diagnostic performance (AUC=0,89, CI95%=0,82-0,9630, p<0,0001) (fig. 4). At a cut-off value <6,47 ng/dl, BDNF showed a specificity of 75% and a sensibility of 92,31%,(CI 95%=79,68-97.35) for FM identification (LR=3,692).Conclusion:FM clinical manifestations are strongly dependant from gender. While females present a more severe disease and a higher burden of symptoms, mood disorders tend to be a major characteristic of males with FM. Reduced BDNF serum levels have been reported as typical of depressive disorders. Our findings of lower BDNF levels in male FM patients compared to females support this hypothesis. BDNF have potential as biomarker of the disease and should be validated in larger cohorts.References:[1]Sarzi-Puttini et al. Nature Reviews 2020[2]Colucci-D'Amato et al. Int J Molecular Sciences 2020[3]Nugraha et al. Rheumatol Int 2012[4]Schmitt et al. Ann Med 2016[5]Melchior et al. Neuroscience 2016[6]Stefani et al. Neuroscience Letters 2012Disclosure of Interests:None declare

Gellan hydrogel as a powerful tool in paper cleaning process: a detailed study

Hypothesis: Wet cleaning of ancient papers is one of the most critical steps during a conservation treatment. It is used to improve the optical qualities of a graphic work and remove dust and by-products resulting from cellulose degradation. Nevertheless, washing treatment usually involves a substantial impact on the original morphological structure of paper and can sometimes be dangerous for water sensitive inks and pigments. Experiments: The use of rigid hydrogel of Gellan gum as an alternative paper cleaning treatment is developed. The application of a rigid hydrogel minimizes damages caused by the use of water, and therefore is much more respectful for the original integrity of ancient paper. Findings: Gellan hydrogel has been used to clean paper samples belonging to different centuries (from XVI to XIX) and therefore, characterized by a different story in terms of degradation condition and paper composition. Several techniques, such as high-performance liquid chromatography, Fourier transform infrared spectroscopy, scanning electron microscopy and pH measurements, has been employed to assess the effectiveness and safety of the proposed cleaning method

POS1464-HPR ASSESSMENT OF EMOTIONAL WELL-BEING IN RHEUMATIC PATIENTS DURING COVID-19 LOCKDOWN THROUGH A WEB-BASED SURVEY APPROACH

Background:The severe measures of lockdown imposed in Italy to limit the SARS coronavirus 2 disease (COVID-19) spread caused an increase of reported anxiety, depression and suicidal rate among general population. Patients affected by rheumatic disorders feature an increased risk of mood disorders for the chronic course of the disease itself and for the related disability.Objectives:Aim of this study was to investigate the impact of COVID-19 lockdown on emotional well-being of a large cohort of rheumatic patients through a telemedicine approach.Methods:Patients in follow-up in rheumatologic out-patient clinics of our hospital were invited to participate to an online survey. They were asked also to invite their best friend, matched for age and sex, to participate the survey, as control group. The online survey included demographic questions and validated, psychometric scales for stress vulnerability (Stress Vulnerability Scale-SVS), resilience (Resilience Scale-RS), depression (Zung's depression questionnaire-Zung-D) and anxiety (Zung's anxiety questionnaire-Zung-A) evaluation.Results:The cohort was composed by 484 subjects (84,1% F, 15,9% M). The number of subjects and the frequency of various diagnosis are shown in Table 1. According to the psychometric scales, 55,5% and 43,3% of subject showed respectively an increased stress vulnerability and a reduced resiliency. Moreover, 64% and 40,5% of the enrolled subjects reported respectively anxiety and depressive symptoms worthy of psychiatric attention. There was a significant different distribution of scores for SVS (p<0,0001), Zung-A (p<0,0001) and Zung-D (p<0,0001) among the various diagnosis. In comparison with controls, higher scores of SVS were present in connective tissue diseases (CTD) (p=0,007), Sjogren's Syndrome (SSJ) (p=0,0029) and fibromyalgia (FM) (p<0,0001) patients, higher scores of Zung-A were present in SSJ (p=0,006) and FM (p<0,0001) patients and higher scores of Zung-D were present in FM (p<0,0001) patients (Figure 1). Ordinal regression analysis showed that higher classes of anxiety were independently predicted by the Tension (β=0,32;CI=0,13-0,52;p=0,003) and Demoralization (β=0,22;CI=0,04-0,44;p=0,046) components of SVS and by the Zung-D score (β=0,09;CI=0,05-0,1;p<0,001), while higher classes of depression were independently predicted by SVS total (β=0,17;CI=0,03-0,30;p=0,012), by its subcomponent Demoralization (β=0,22;CI=0,01-0,43;p=0,038), by a lower absolute RS score (β=-0,083;CI=-0,1--0,06;p<0,001) and by the Zung-A score (β=0,11;CI=0,06-0,15;p<0,001). In both cases, a specific diagnosis was not associated to a higher risk of advanced anxiety and depression classes.Conclusion:Rheumatic patients developed a high frequency of anxiety and depressive symptoms following COVID-19 lockdown, of which a large part should be referred for specialist attention according to their severity. There was a large variability of the symptoms reported among the various diagnosis. CTD, SSJ and FM patients were the most susceptible to the development of anxiety, depression and stress vulnerability. The application of psycometric scales through a telemedicine approach represents a useful tool to identify patients with higher levels of anxiety and depression.Table 1.DIAGNOSISFrequencyPercentControls459,3RA8216,9PSA214,3UA40,8SPA71,4CTD7014,5FM7916,3Myositis81,7Behcet's112,3Vasculitis163,3APS61,2Other AID132,7SSJ12225,2Total484100RA: Rheumatoid Arthritis, PSA: Psoriatic Arthritis; UA: Undifferentiated Arthritis; SPA: Spondyloarthritis; CTD: Connective tissues diseases (including Systemic Lupus Erythematosus, Scleroderma, Undifferentiated Connettivitis, Mixed Connettivitis); FM: Fibromyalgia; APS: Anti-phospholipid syndrome; Other AID: Other autoimmune/inflammatory disorders (including Adult-onset Still disease, IgG4 related disease); SSJ: Sjogren SyndromeFigure 1.Disclosure of Interests:None declare

MINT, the molecular interaction database: 2012 update

The Molecular INTeraction Database (MINT, http://mint.bio.uniroma2.it/mint/) is a public repository for protein-protein interactions (PPI) reported in peer-reviewed journals. The database grows steadily over the years and at September 2011 contains approximately 235,000 binary interactions captured from over 4750 publications. The web interface allows the users to search, visualize and download interactions data. MINT is one of the members of the International Molecular Exchange consortium (IMEx) and adopts the Molecular Interaction Ontology of the Proteomics Standard Initiative (PSI-MI) standards for curation and data exchange. MINT data are freely accessible and downloadable at http://mint.bio.uniroma2.it/mint/download.do. We report here the growth of the database, the major changes in curation policy and a new algorithm to assign a confidence to each interaction

Identification of MOR-positive B cell as possible innovative biomarker (Mu lympho-marker) for chronic pain diagnosis in patients with fibromyalgia and osteoarthritis diseases

Fibromyalgia (FM) diagnosis follows the American College of Rheumatology (ACR) criteria, based on clinical evaluation and written questionnaires without any objective diagnostic tool. The lack of specific biomarkers is a tragic aspect for FM and chronic pain diseases in general. Interestingly, the endogenous opioid system is close to the immune one because of the expression of opioid receptors on lymphocytes membrane. Here we analyzed the role of the Mu opioid receptor on B lymphocytes as a specific biomarker for FM and osteoarthritis (OA) patients. We enrolled three groups of females: FM patients, OA patients (chronic pain control group) and healthy subjects (pain-free negative control group). We collected blood samples to apply immunophenotyping analysis. Written tests were administrated for psychological analysis. Data were statistically analyzed. Final results showed that the percentage of Mu-positive B cells were statistically lower in FM and OA patients than in pain-free subjects. A low expression of Mu-positive B cell was not associated with the psychological characteristics investigated. In conclusion, here we propose the percentage of Mu-positive B cells as a biological marker for an objective diagnosis of chronic pain suffering patients, also contributing to the legitimacy of FM as a truly painful disease

The IMEx coronavirus interactome: an evolving map of Coronaviridae-host molecular interactions

The current coronavirus disease of 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus (SARS-CoV)-2, has spurred a wave of research of nearly unprecedented scale. Among the different strategies that are being used to understand the disease and develop effective treatments, the study of physical molecular interactions can provide fine-grained resolution of the mechanisms behind the virus biology and the human organism response. We present a curated dataset of physical molecular interactions focused on proteins from SARS-CoV-2, SARS-CoV-1 and other members of the Coronaviridae family that has been manually extracted by International Molecular Exchange (IMEx) Consortium curators. Currently, the dataset comprises over 4400 binarized interactions extracted from 151 publications. The dataset can be accessed in the standard formats recommended by the Proteomics Standards Initiative (HUPO-PSI) at the IntAct database website (https://www.ebi.ac.uk/intact) and will be continuously updated as research on COVID-19 progresses

Preliminary identification of key clinical domains for outcome evaluation in fibromyalgia using the Delphi method : the Italian experience

Objective: Fibromyalgia (FM) is a complex syndrome that, in Italy, affects at least 2% of the adult population. It is characterized by chronic widespread musculoskeletal pain often accompanied by multiple other symptoms. The aim of this study was to identify a set of clinical domains for FM considered relevant by both clinicians and patients using a consensus process. Methods: Consensus was achieved using the Delphi method based on questionnaires and systematic, controlled opinion feedback. The Delphi exercise involved a panel of 252 rheumatologists and 86 patients with FM as defined by the American College of Rheumatology criteria. All of the patients and clinicians were asked to rank the relative different domains of FM in order of priority. The content validity index (CVI) was used to establish the percentage agreement. The importance of each item was ranked on a 0-3 Likert scale. The frequency, mean relevance scores, and frequency importance product were also calculated. Results: The Delphi exercise showed that the domains ranked highest by patients were similar to those of the clinicians, with the exception of tender point intensity (considered relevant by the clinicians but not by the patients) and environmental sensitivity (considered important by the patients but not by the clinicians). A final 8-item model was developed which was considered to demonstrate adequate validity. Conclusions: The Delphi exercises identified and ranked relevant key clinical domains that need to be assessed in FM research. On the basis of these results, a new patient-reported composite outcome index can be developed and used in clinical trials