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Background: In psoriatic arthritis (PsA), musculoskeletal ultrasound is a complementary tool to physical examination, useful even in patients in remission to detect subclinical activity. Objectives: The objective of the study was to assess the ultrasound prevalence of active enthesitis and synovitis in patients who reached the therapeutic target. Methods: This cross-sectional study included patients with at least 6 months of therapy with a targeted synthetic or biological disease-modifying antirheumatic drug who were in treatment target (i.e., DAPSA < 14). Patients underwent bilateral clinical and ultrasound examination of the elbow lateral epicondyle, quadriceps insertion, distal patellar tendon insertion, and Achilles enthesis for assessing enthesitis, and hand and foot joints for assessing synovitis. Enthesitis and synovitis were considered active if the power Doppler signal showed at least a score of one. Results: The study included 51 PsA patients, women (52.9%), with an average age of 55 years. Although the patients were within the DAPSA treatment target, 21.6% had at least one painful enthesis at clinical examination, 19.6% had ultrasound evidence of at least one active enthesitis and 15.7% had ultrasound signs of at least one active synovitis. Conclusions: Among PsA patients thought to be within the therapeutic target, ultrasound detected a non-negligible percentage of active enthesitis and synovitis.

Two series, " a " and " b ", each consisting of nine chemical compounds, with 2,3-disubstituted quinazolin-4(3H)-one scaffold, were synthesized and evaluated for their anticonvulsant activity. They were investigated as dual potential positive allosteric modulators of the GABA A receptor at the benzodiazepine binding site and inhibitors of carbonic anhydrase II. Quinazolin-4(3H)-one derivatives were evaluated in vivo (D 1-3 = 50, 100, 150 mg/kg, administered intraperitoneally) using the pentylenetetrazole (PTZ)-induced seizure model in mice, with phenobarbital and diazepam, as reference anticonvulsant agents. The in silico studies suggested the compounds act as anticonvulsants by binding on the allosteric site of GABA A receptor and not by inhibiting the carbonic anhydrase II, because the ligands-carbonic anhydrase II predicted complexes were unstable in the molecular dynamics simulations. The mechanism targeting GABA A receptor was confirmed through the in vivo flumazenil antagonism assay. The pentylenetetrazole experimental anticonvulsant model indicated that the tested compounds, 1a - 9a and 1b - 9b , present a potential anticonvulsant activity. The evaluation, considering the percentage of protection against PTZ, latency until the onset of the first seizure, and reduction in the number of seizures, revealed more favorable results for the " b " series, particularly for compound 8b .

Lipophilicity, a significant physicochemical parameter of bioactive molecules, along with absorption, distribution, metabolism, excretion parameters and toxicity risk, was investigated for 32 thiazolo[3,2-b][1,2,4]triazole and imidazo[2,1-b][1,3,4]thiadiazole derivatives with anti-inflammatory potential. The experimental lipophilicity study was carried out by reversed-phase thin-layer chromatography in a binary isopropanol-water mobile phase, and the obtained results were compared with the theoretical lipophilicity parameters estimated by various computational methods. Strong correlations were found between the experimental retention factors and calculated partition coefficients. A modified Petra/Osiris/Molinspiration analysis was performed on the previously synthesized compounds, using SwissADME, Osiris and Molinspiration web tools. The predicted in silico parameters highlighted the most promising compounds as potential drug candidates. The compounds showed good gastrointestinal absorption, moderate activity according to the bioactivity score (values situated between -1.25 and -0.06), and a safe toxicity profile. The results obtained in this study will contribute to lipophilicity studies and other future studies focused on modulating new drug candidates starting from thiazolo[3,2-b][1,2,4]triazole and imidazo[2,1-b][1,3,4]thiadiazole derivatives, which are important heterocycles in medicinal chemistry.

The current study aimed to evaluate rheumatoid arthritis (RA) patients with interstitial lung disease (ILD) in clinical practice and whether disease characteristics are associated with X-ray and high-resolution computed tomography (HR-CT) findings. Medical history of RA patients from a tertiary rheumatology clinic was retrieved from its electronic database starting from 1 January 2019 until the study date (8 August 2022) using International Classification of Disease version 10 codes for RA, ILD and exclusion criteria. The study included 78 RA patients (75.6% women, 15.4% active smokers), with average time from RA to ILD of 5.6 years. Regarding chest X-ray findings, men had a higher prevalence of nodules, combined fibrosis and nodules and combined bronchiectasis and nodules, rheumatoid factor (RF)-positive patients had a higher prevalence of fibrosis and anti-cyclic citrullinated peptide antibodies (ACPA)-positive patients had a higher prevalence of bronchiectasis. Regarding HR-CT findings, patients actively treated with methotrexate had a higher prevalence of nodules; a combination of fibrosis and nodules; combination of emphysema and nodules; and combination of fibrosis, emphysema and nodules. ILD develops within approximately 5 years from RA diagnosis, and ILD-associated imaging findings on chest X-rays and HR-CT are more prevalent among men with RA, among patients with positive RA serology (RF and/or ACPA) and RA patients on methotrexate.

Background: Pharmacogenetics (PGx) is an important component of personalized medicine that has the potential to improve medicines' effectiveness and safety. However, despite progress in technology and availability, PGx testing application into patient-care in Eastern Europe countries, has been slow. Objectives: Our aim was to describe knowledge and attitudes of Romanian pharmacists concerning PGx, and identify potential factors limiting PGx implementation. Method: An anonymous, web-based questionnaire was distributed to Romanian pharmacists registered in the National Pharmacists' Association (NPA) via an official e-mail sent by NPA representatives. Results: A total of 1,058 pharmacists completed the questionnaires, resulting in a response rate of 7.6%. Pharmacists were predominantly female (90.1%), younger than 49 years (87.5%) and mostly worked in community pharmacies (80.2%). Most pharmacists (64.8%) had a knowledge score between 30 and 49 points out of 60, and (75.4%) had attitude scores between 9 and 7 out of 10. Attitude and knowledge scores positively correlated. Conclusion: Despite performing fairly well on general questions regarding PGx, Romanian pharmacists may lack in-depth knowledge, which can affect their readiness to discuss PGx information with patients or other healthcare professionals. High pricing was considered an important impediment in PGx implementation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pop, Cristina, Iaru, Popa and Mogoșan.)

The aim of the present study was to investigate the polyphenolic profile and the anti-inflammatory and anti-nociceptive activities of four traditionally used medicinal plants from Burkina Faso: Parkia biglobosa, Detarium microcarpum, Vitellaria paradoxa and Sclerocarya birrea. The analysis of the main phenolic compounds was performed by the HPLC-UV-MS method. The anti-inflammatory effect of the aqueous bark extracts was investigated by the λ-carrageenan-induced rat paw edema test. The anti-nociceptive activity was evaluated by the Randall−Selitto test under inflammatory conditions. Seven phenolic acids (gallic, protocatechuic, gentisic, vanillic, p-coumaric, ferulic, and syringic acids), and three flavonoids (catechin, epicatechin, and quercitrin) were identified in the plant samples. High contents of gallic acid were determined in the D. microcarpum, P. biglobosa and S. birrea extracts (190−300 mg/100 g), and V. paradoxa extract was the richest in epicatechin (173.86 mg/100 g). The λ-carrageenan-induced inflammation was significantly reduced (p < 0.001) by the P. biglobosa and D. microcarpum extracts (400 mg/kg p.o.). Under the inflammatory conditions, a significant anti-nociceptive activity (p < 0.001) was obtained after 2−3 h from the induction of inflammation. The effects of the tested extracts could be related to the presence of polyphenols and could be useful in the management of certain inflammatory diseases.

Obesity induces hemodynamic and humoral changes that are associated with functional and structural cardiac remodeling, which ultimately result in the development of heart failure (HF) with preserved ejection fraction (HFpEF). In recent years, pharmacological studies in patients with HFpEF were mostly unsatisfactory. In these conditions, alternative new therapeutic approaches are necessary. The aim of our study was (1) to assess the effects of obesity on heart function in an experimental model and (2) to evaluate the efficacy of an alpha-lipoic acid (ALA) antioxidant treatment. Sprague-Dawley rats (7 weeks old) were either included in the control group ( n = 6) or subjected to abdominal aortic banding (AAB) and divided into three subgroups, depending on their diet: standard (AAB + SD, n = 8), hypecaloric (AAB + HD, n = 8) and hypercaloric with discontinuous ALA treatment (AAB + HD + ALA, n = 9). Body weight (BW), glycemia, echocardiography parameters and plasma hydroperoxides were monitored throughout the study. After 36 weeks, plasma adiposity (leptin and adiponectin) and inflammation (IL-6 and TNF-alpha) markers, together with B-type natriuretic peptide and oxidative stress markers (end-products of lipid peroxidation and endogenous antioxidant systems) were assessed. Moreover, cardiac fiber diameters were measured. In our experiment, diet-induced obesity generated cardiometabolic disturbances, and in association with pressure-overload induced by AAB, it precipitated the onset of heart failure, cardiac hypertrophy and diastolic dysfunction, while producing a pro-oxidant and pro-inflammatory plasmatic status. In relationship with its antioxidant effects, the chronic ALA-discontinuous treatment prevented BW gain and decreased metabolic and cardiac perturbations, confirming its protective effects on the cardiovascular system.

Introduction: Important drug safety issues are evaluated through a referral procedure in the EU by the Pharmacovigilance Risk Assessment Committee (PRAC) within the European Medicines Agency. We aim to describe all safety-related referrals assessed by the PRAC by June 2019., Methods: Publicly available data on safety issues assessed through referral procedures that reached a final decision during July 2012-June 2019 were identified, analyzed and classified according to predefined criteria., Results: Fifty-one safety issues were assessed by PRAC for 45 medicines/combinations/therapeutic classes during this timeframe. Referrals were initiated mostly by the European Commission (16) and France (8). Nine medicines were authorized in the last five years, the rest being well-established drugs. In four cases (flupirtine, hydroxyethyl-starch, valproate, codeine) PRAC re-assessed the same risks as previous recommendations have not been effective. Post-referral recommendations consisted of updates of the summary of product characteristics and package leaflet (42), Direct Healthcare Professional Communication (32), and other additional risk minimization measures (RMMs). Withdrawal was recommended for seven active substances., Conclusions: PRAC recommended routine or additional RMMs for most referrals. Complete withdrawal of a drug or withdrawal of certain pharmaceutical forms or concentrations was advised only when the risk could not be managed by RMMs.

Despite recent advances in disease management and prevention, heart failure (HF) prevalence is still high. Hypertension, inflammation and oxidative stress are being investigated as important causative processes in HF. L. barbarum L. polysaccharides (LBPs) are widely used for their anti-inflammatory and antioxidant properties. Thus, the aim of the present study was to evaluate the effects of LBPs on inflammation and oxidative stress markers in a pressure overload-induced HF rat model, surgically induced by abdominal aorta banding in Wistar rats (AAB) ( n = 28). Also, control rats ( n = 10) were subjected to a sham operation. After echocardiographic confirmation of HF (week 24), AAB rats were divided into three groups: rats treated with LBPs for 12 weeks: 100 mg/kg body weight /day (AAB&#95;100, n = 9), 200 mg/kg body weight /day (AAB&#95;200, n = 7) and no-treatment group (control AAB, n = 12). After 12 weeks of treatment with LBPs, the decline of cardiac function was prevented compared to the control AAB rats. Treatment with 200 mg/kg body weight /day LBPs significantly reduced the inflammation as seen by cytokine levels (IL-6 and TNF-α) and the plasma lipid peroxidation, as seen by malondialdehyde levels. These results suggest that LBPs present anti-inflammatory and antioxidant effects with utility in a HF animal model and encourage further investigation of the cardioprotective effects of these polysaccharides., Competing Interests: The authors declare no conflicts of interest.

Objective: The study aims to compare the efficacy and safety of biosimilar etanercept (SB4) to original etanercept (ETN) in a real-life national cohort of rheumatoid arthritis (RA)., Methods: Data from RA patients were retrieved electronically from the Romanian Registry of Rheumatic Diseases (RRBR), which contains all patients receiving biologics in the country., Results: The study included 242 patients with efficacy and safety data after 6 months of treatment: 123 (50.8%) with ETN, 119 (49.2%) with SB4. There were no significant differences after 6 months regarding composite scores of RA activity between patients on ETN and SB4 (e.g. DAS28 remission: 18.7% in ETN group and 17.6% in SB4 group, p = 0.823; Boolean remission: 11.4% in ETN group and 11.8% in SB4 group, p = 0.926). There were 11 adverse events (AE) in the ETN subgroup (including 3 severe AE: lower respiratory tract infection, enterocolitis and anaphylaxis) and 12 AE in SB4 subgroup (including 4 severe AE: lower respiratory tract infection, vasculitis, anaphylaxis and rash)., Conclusion: Biosimilar and original etanercept showed similar efficacy and safety after the first 6 months of treatment in RA patients from a national registry, which brings further evidence for biosimilarity in unselected patients in real-world setting., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Rheumatoid arthritis (RA) is associated with increased costs generated by resource utilization and loss of work productivity. We have studied 206 RA patients and analyzed indirect costs of RA in Romania (estimated using the human capital approach) in comparison with reported data for other countries. Data were collected using self-reported questionnaires. The average age at inclusion was 55 years, with mean disease duration of 9.4 years; 55 patients had permanent work disability due to RA; 6.35 days of sick leave per patient were reported for the entire year of follow-up; the cost of permanent work disability was 1256€ per patient. From a societal perspective, the average indirect costs for a patient with RA were 1506€, significantly lower than the ones reported by other countries, especially due to the low monetary value of paid work.

Background: Safety monitoring of all drugs throughout their entire life cycle is mandatory in order to protect the public health. Our objective was to describe all new safety signals assessed at EU level by the Pharmacovigilance Risk Assessment Committee (PRAC)., Methods: Publicly available data on signals assessment from PRAC meeting minutes for the period January 2014-November 2017 were analyzed and classified., Results: A total of 239 new signals for 194 drugs/drug combinations/therapeutic classes were evaluated by PRAC. A total of 154 signals were triggered by spontaneous reporting, 31 by literature case reports, and 26 by observational studies. In 188 signals, the drugs involved were authorized for more than 5 years. The drug classes for which most signals were detected were antineoplastic/immunomodulators (n = 75), anti-infectives (n = 34), and drugs acting on the nervous system (n = 27). Signals were triggered for drug interactions (n = 15), in utero exposure (n = 7), medication errors (n = 6), and for different disorders, among which the skin/subcutaneous tissue disorders were more common. PRAC recommendations consisted in label updates (n = 86), in Direct Healthcare Professional Communications (n = 17), and in eight recommendations for a more complex evaluation through referral procedures., Conclusions: Most new signals assessed were triggered by spontaneous reporting and led to routine risk minimization measures, such as updating the product information.

Non-steroidal anti-inflammatory drugs (NSAIDs) are an important pharmacological class of drugs used for the treatment of inflammatory diseases. They are also characterized by severe side effects, such as gastrointestinal damage, increased cardiovascular risk and renal function abnormalities. In order to synthesize new anti-inflammatory and analgesic compounds with a safer profile of side effects, a series of 2,6-diaryl-imidazo[2,1- b ][1,3,4]thiadiazole derivatives 5a ⁻ l were synthesized and evaluated in vivo for their anti-inflammatory and analgesic activities in carrageenan-induced rat paw edema. Among all compounds, 5c showed better anti-inflammatory activity compared to diclofenac, the standard drug, and compounds 5g , 5i , 5j presented a comparable antinociceptive activity to diclofenac. None of the compounds showed ulcerogenic activity. Molecular docking studies were carried out to investigate the theoretical bond interactions between the compounds and target, the cyclooxygenases (COX-1/COX-2). The compound 5c exhibited a higher inhibition of COX-2 compared to diclofenac.

This study was performed to evaluate the phenolic profile, antioxidant and diuretic effects of black cumin and lady-in-a-mist seeds. In the phenolic profile, differences between the two species are significant. Qualitative and quantitative analyses of the phenolic compounds were performed using a HPLC-UV/MS method. Hyperoside was the only identified flavonoid glycoside (1.08 ± 0.01 μg∙g-1 dw plant material), in the N. damascena extract. Regarding the flavonol profile, kaempferol was identified before the hydrolysis, only in the N. sativa extract (6.06 ± 0.02 μg∙g-1 dw plant material) and quercetin only in N. damascena seeds (14.35 ± 0.02 μg∙g-1 dw plant material). The antioxidant potential of the two species was tested through several electron transfer assays, which indicated, excepting for the FRAP assay, N. damascena as exhibiting a higher free radical scavenging activity. The diuretic activity of the two extracts was tested using a rat-experimental model on acute diuresis. Administration of the ethanolic extract of N. sativa (100 mg∙kg-1) resulted in a significant increase in urine volume, although less than found with the reference drug; in addition N. damascena extract did not present a diuretic effect. In reference to the elimination of Na+, K+ and uric acid, the black cumin extract exhibited a higher natriuretic than kaluretic effect and a similar uricosuric effect with control and N. damascena. For N. damascena, the Na+/K+ ratio was sub unitary, but not due to an increasing of the kaluretic effect, but mostly to a decrease of Na+ excretion.