Search Results (309)

Background: Rheumatoid arthritis (RA) is a debilitating autoimmune disorder characterized by chronic inflammation and joint damage. Despite advancements in treatment, complete remission remains elusive. Methods: In this study, we introduce a novel lipid nanoparticle formulation co-delivering hydroxychloroquine (HCQ) and siRNA targeting TNF-α (siTNF-α) using microfluidic technology, marking the first use of such a combination for RA therapy. Results: In LPS-stimulated RAW 264.7 cells, the nanoparticles effectively reduced inflammatory markers. When administered via an intra-articular injection in a rat model, they significantly decreased joint inflammation and demonstrated good biological safety. Conclusions: This pioneering approach highlights the potential of lipid nanoparticles as a dual-delivery platform for enhanced RA treatment through targeted intra-articular administration. Full article

Background/Objectives: Preclinical studies have shown that the anti-malarial drug hydroxychloroquine (HCQ) improves the anti-cancer effects of various therapeutic agents by impairing autophagy. These findings are difficult to translate in vivo as reaching an effective HCQ concentration at the tumor site for extended times is challenging. Previously, we found that free HCQ in combination with gefitinib (Iressa^®, ZD1839) significantly reduced tumor volume in immunocompromised mice bearing gefitinib-resistant JIMT-1 breast cancer xenografts. Here, we sought to evaluate whether a liposomal formulation of HCQ could effectively modulate autophagy in vivo and augment treatment outcomes in the same tumor model. Methods: We developed two liposomal formulations of HCQ: a pH-loaded formulation and a formulation based on copper complexation. The pharmacokinetics of each formulation was evaluated in CD1 mice following intravenous administration. An efficacy study was performed in immunocompromised mice bearing established JIMT-1tumors. Autophagy markers in tumor tissue harvested after four weeks of treatment were assessed by Western blot. Results: The liposomal formulations engendered ~850-fold increases in total drug exposure over time relative to the free drug. Both liposomal and free HCQ in combination with gefitinib provided comparable therapeutic benefits (p > 0.05). An analysis of JIMT-1 tumor tissue indicated that the liposomal HCQ and gefitinib combination augmented the inhibition of autophagy in vivo compared to the free HCQ and gefitinib combination as demonstrated by increased LC3-II and p62/SQSTM1 (p62) protein levels. Conclusions: The results suggest that liposomal HCQ has a greater potential to modulate autophagy in vivo compared to free HCQ; however, this did not translate to better therapeutic effects when used in combination with gefitinib to treat a gefitinib-resistant tumor model. Full article

Introduction: The autoimmune/inflammatory syndrome induced by adjuvants (ASIA) is a rare condition caused by an immune response associated with over-reactivity of the immune system, triggered by adjuvants. The most common adjuvants are aluminium salts but can also be bioimplants or infectious agents. It may lead to the development of various autoimmunologic diseases. Case Report: In the following article, we present the case of a 26-year-old woman who developed SLE likely induced by ASIA syndrome after the aesthetic medicine procedures. The patient was admitted because of arthralgia and fever. She also presented with a butterfly-shaped erythema on her face and erythematous and infiltrative skin lesions on the posterior surface of the thighs and buttocks. We performed numerous diagnostic tests, including laboratory tests, immunological tests, imaging diagnostics such as chest X-ray and USG of the abdomen and joints, and the biopsy of the skin lesion on the left thigh. The results of the diagnostic process led us to diagnose SLE. The patient fulfilled the ACR/EULAR 2019 classification criteria of the SLE. Laboratory results also led to the diagnosis of autoimmune haemolytic anaemia. Due to exposure to numerous adjuvants like tattoo ink, hyaluronic acid, and piercing and the development of the delayed inflammatory reaction (DIR) to hyaluronic acid (HAF), the patient also fulfilled the criteria of ASIA. In the treatment process we applied antibiotics, non-steroidal anti-inflammatory drugs (NSAIDs), steroids, hydroxychloroquine, and cyclosporine. The treatment resulted in an improvement in the general condition, resolution of swelling and joint pain, and improvement in skin lesions. Conclusions: ASIA syndrome after bioimplantation is still underdiagnosed, probably due to ignorance or diagnostic difficulties, as symptoms are uncharacteristic and there is no immunological marker for this syndrome. In addition, as in the presented case, it can develop several years after the procedure, and it is difficult for both patient and physician to become aware of the connection. Early diagnosis requires a multidisciplinary approach and may require immunosuppressive treatment in specific cases. Full article

Background/Objectives: Although hydroxychloroquine (HCQ) is used to treat systemic lupus erythematosus (SLE), it is associated with retinal toxicity. Early diagnosis can prevent the further progression of HCQ-associated retinopathy by discontinuing HCQ treatments. This study aimed to evaluate the early diagnostic parameters in patients with SLE treated with HCQ and identify the best approach using multifocal electroretinography (mfERG) and swept-source optical coherence tomography (SS-OCT) to reflect subclinical retinal toxicity. Methods: Thirty-eight patients with SLE (76 eyes) and 18 healthy controls (36 eyes) were enrolled. They were referred for HCQ retinopathy screening without visual field defects. The patients were tested using a standard 61-hexagon mfERG stimulus and SS-OCT. Ten groups of the mfERG responses from the sectors were averaged to compare the quadrants, hemiretinal areas, consecutive ring amplitudes, and ring ratios (R1/R2–R5) from the center to the periphery. Additionally, the ganglion cell complex (GCC) analyses were performed using SS-OCT. Results: No difference was observed in GCC thickness on the OCT images, in the P1 amplitudes, and in the implicit time of mfERG. However, the R1/Rx ring ratios, except the R1/R2 ratio, showed significant differences among the three groups (p = 0.759, 0.018, 0.029, and 0.029, respectively). The R1/R3, R1/R4, and R1/R5 ring ratios demonstrated a correlation with the duration of HCQ therapy (r = −0.303, −0.279, and −0.266; p = 0.003, 0.006, and 0.009). The areas under the receiver operating characteristic curve of the ring ratios R1/R3–R5 were 0.730, 0.702, and 0.724, respectively (p = 0.004, 0.012, and 0.006), indicating the likelihood of being categorized as a high-risk group for subclinical HCQ retinopathy. Conclusions: The ring ratio of mfERG reflects the subclinical electrophysiological alterations induced by HCQ and can become more clinically useful by simplifying screening examinations. Full article

Challenges in the treatment and removal of recalcitrant emerging organic pollutants in wastewater prompt the development of advanced oxidative processes (AOPs). Hydroxyl radicals are non-specific and capable of reacting with a diverse range of pollutants of emerging concern. In this study, hydroxychloroquine (HCQ) was removed from aqueous solutions with removal efficiencies between 80 and 90%. The presence of H₂O₂, humic acid, and other inorganic ions negatively influenced the degradation efficiency. However, the presence of S₂O₈²⁻ was found to increase the removal efficiency, which was attributed to the formation of SO₄^•− in addition to •OH radicals. Additionally, Fenton-assisted electron beam treatment showed an improved removal of 2.88 × 10⁻⁴ M of HCQ with an average improvement of ≈10% at doses between 0.5 to 2.0 kGy in addition to the total organic carbon and chemical oxygen demand reduction. The H₂O₂ concentration and molar ratio of H₂O₂: Fe²⁺ influenced the removal capacity of the Fenton-assisted electron beam process. A degradation mechanism for HCQ has been proposed based on the reactions of •OH radicals and e_aq⁻. Full article

Hearing impairment in patients with rheumatoid arthritis has been underestimated for decades. Rheumatoid arthritis can affect both the middle ear (specifically, the incudomalleolar and incudostapedial joints) and inner ear (including the cochlea and acoustic nerve) simultaneously. Despite ongoing research, consensus on effective treatments for hearing impairment in these patients remains elusive. This systematic review aims to consolidate clinically relevant information for healthcare providers by summarizing current evidence on hearing impairment in rheumatoid arthritis patients. We conducted the current systematic review by searching platforms of PubMed, Embase, ClinicalKey, Web of Science, and ScienceDirect to retrieve eligible articles regarding hearing impairment related to rheumatoid arthritis. We extract any data on characteristics, pathophysiology, examination, and treatment related to rheumatoid arthritis. Based on the currently available evidence, we advocate for the use of specific audiometric tests to facilitate early detection of hearing impairment in these patients. Regular audiological assessments are recommended to monitor hearing ability and potentially prevent further deterioration. Finally, we propose a modified treatment protocol that integrates steroids, hydroxychloroquine, and non-invasive brain stimulation as a novel therapeutic approach for managing these symptoms. This protocol aims to offer clinicians new strategies to address hearing impairment in patients with rheumatoid arthritis effectively. Full article

Improper use of hydroxychloroquine to treat COVID-19 has been linked to 17,000 preventable deaths. This content analysis study investigates the emergence of this conspiracy theory, the role of the news media in perpetuating and disseminating it, and whether coverage differed by outlet political alignment. We searched Nexis for relevant media from 17–31 March 2020. A total of 128 media pieces were coded qualitatively and thematically analysed. The news media amplified the voices of right-wing political elites and used a variety of manipulative tactics in reporting on hydroxychloroquine. Powerful ingroup/outgroup mechanisms polarised the American public and created a schism between Trump supporters and the public health apparatus that reflected the political asymmetry in reporting on hydroxychloroquine. The widespread use of optimistic framings and anecdotal evidence contributed to public misunderstandings of the evidence. Therefore, strategic and interventionist public health efforts are required to combat misinformation. This study informs discussions of how politicised media coverage catalyses conspiracism. Full article

Background and Objectives: It is known that critical illness and associated neuromuscular problems begin to appear in patients hospitalized in the intensive care unit (ICU) for more than a week. The goal of this study was to research the role of hydroxychloroquine (HCQ) in the treatment of cytokine storm and critical illness neuromyopathy (CINM) in a rat sepsis model. Materials and Methods: Rats were assigned into three groups, and a feces intraperitoneal-injection group (FIP) procedure was carried out on 30 rats to induce a model of sepsis for critical illness polyneuromyopathy (CINM). The study groups were as follows: Group 1: control (nonoperative and orally fed control, n = 10), Group 2: FIP with 0.9% NaCl saline was given as 1 mL/kg/day by oral gavage (n = 10), and Group 3: FIP with 10 mg/kg/day of hydroxychloroquine (Plaquenil 200 mg) administered by oral gavage (n = 10). Electrophysiological recordings (EMG) were conducted six days after surgery. EMG was carried out three times on the right sciatic nerve, which was stimulated with supramaximal intensity utilizing a bipolar needle electrode at the sciatic notch. Tumor necrosis factor-alpha (TNF-α), malondialdehyde (MDA), lactic acid levels, and interleukin-6 (IL-6) were evaluated. Results: In terms of TNF-α, MDA, lactic acid levels, and IL-6, there was a statistically significant decrease in the CINM + 10 mg/kg HCQ group compared to the CINM and saline group (p < 0.0001, p < 0.05, p < 0.05, and p < 0.05, respectively). Compound muscle action potentials (CMAPs) latency and duration were decreased in the CINM + 10 mg/kg HCQ group compared to other groups (p < 0.01 and p < 0.001). However, CMAP amplitude was significantly higher in the CINM + 10 mg/kg HCQ group unlike the CINM and saline group (p < 0.001). Conclusions: This is the first study to demonstrate the effects of HCQ on CINM in a rat model of sepsis. The findings of our research suggest that hydroxychloroquine may be used as a potential therapeutic agent in the treatment of sepsis. Hydroxychloroquine may have an important effect in the pathogenesis of sepsis-associated CINM by reducing cytokine production and oxidative stress. Full article

Background/Objectives: Prolonged remission on low-dose glucocorticoids (GC) is a main goal in patients with systemic lupus erythematosus (SLE). The aim of this study is to assess whether GC ≤ 5 mg/d increases the risk of damage accrual in patients with SLE in prolonged remission. Methods: Observational study of routine clinical care data of the inception Lupus Cruces-Bordeaux cohort. Only patients in DORIS remission during five consecutive yearly visits were included. The endpoint was damage accrual during the 5-year follow-up, either global or specific damage: GC-induced, cardiovascular (CV), lupus and other. Patients no longer on GC therapy by year 5 (GC5-Off) were compared with those who continued GC therapy (GC5-On). Comparisons were made by Cox and Poisson regressions, which were adjusted with propensity score (PE) in order to control for confounding by indication. Results: 132 patients were included, 56 in the GC5-On and 76 in the GC5-Off groups. All patients were on GC ≤ 5 mg/d for the whole follow-up, the mean prednisone dose in the GC5-On group being 2.96 mg/d during the whole study period and 2.6 mg/d during the 5th year. Fourteen patients (10.6%) accrued damage. More patients in the GC5-On group accrued global damage, 16% vs. 7% in the GC5-Off group, p = 0.08, mainly at CV domains (7% vs. 1%, respectively, p = 0.16). In the PS-adjusted Cox and Poisson regressions, the GC5-On group was not significantly associated with global (p = 0.39) or CV damage accrual (p = 0.62), nor with the absolute (p = 0.40) or CV-restricted final SDI scores (p = 0.63). The C-index of the propensity score model was 0.79. Conclusions: Maintaining doses of prednisone < 5 mg/d in lupus patients in prolonged remission is not associated with an increased risk of damage accrual. Full article

The existing treatments against Trypanosoma evansi are faced with several drawbacks, such as limited drug options, resistance, the relapse of infection, toxicity, etc., which emphasizes the necessity for new alternatives. We synthesized novel metal-based antiparasitic compounds using chitosan, hydroxychloroquine (HC), and ZnO nanoparticles (NPs) and characterized them for size, morphology, chemical interactions, etc. Molecular docking and protein interaction studies were performed in silico to investigate the inhibitory effects of HC, zinc-ligated hydroxychloroquine (HCZnONPs), and chitosan-zinc-ligated hydroxychloroquine (CsHCZnONPs) for two key proteins, i.e., heat shock protein 90 (Hsp90) and trypanothione reductase associated with T. evansi. In vitro trypanocidal activity and the uptake of zinc ions by T. evansi parasites were observed. The formulation was successfully synthesized, as indicated by its size, stability, morphology, elemental analysis, and functional groups. CsHCZnO nanoparticles strongly inhibit both Hsp90 and trypanothione reductase proteins. The inhibition of Hsp90 by these nanoparticles is even stronger than that of trypanothione reductase when compared to HC and HCZnONPs. This suggests that the presence of polymer chitosan enhances the nanoparticles’ effectiveness against the parasite. For the first time, CsHCZnO nanoparticles exhibited trypanocidal activity against T. evansi, with complete growth inhibition being observed at various concentrations after 72 h of treatment. Fluorescent microscopy using FluoZin-3 on T. evansi culture confirmed the presence of zinc on the surface of parasites. This innovative approach has shown promising results in the quest to develop improved antiparasitic compounds against T. evansi with enhanced effectiveness and safety, highlighting their potential as therapeutic agents against trypanosomiasis. Full article

Background: During the coronavirus disease (COVID)-19 pandemic several drugs were used to manage the patients mainly those with a severe phenotype. Potential drugs were used off-label and major concerns arose from their applicability to managing the health crisis highlighting the importance of clinical trials. In this context, we described the mechanisms of the three repurposed drugs [Ivermectin-antiparasitic drug, Chloroquine/Hydroxychloroquine-antimalarial drugs, and Azithromycin-antimicrobial drug]; and, based on this description, the study evaluated the clinical efficacy of those drugs published in clinical trials. The use of these drugs reflects the period of uncertainty that marked the beginning of the COVID-19 pandemic, which made them a possible treatment for COVID-19. Methods: In our review, we evaluated phase III randomized controlled clinical trials (RCTs) that analyzed the efficacy of these drugs published from the COVID-19 pandemic onset to 2023. We included eight RCTs published for Ivermectin, 11 RCTs for Chloroquine/Hydroxychloroquine, and three RCTs for Azithromycin. The research question (PICOT) accounted for P—hospitalized patients with confirmed or suspected COVID-19; I—use of oral or intravenous Ivermectin OR Chloroquine/Hydroxychloroquine OR Azithromycin; C—placebo or no placebo (standard of care); O—mortality OR hospitalization OR viral clearance OR need for mechanical ventilation OR clinical improvement; and T—phase III RCTs. Results: While studying these drugs’ respective mechanisms of action, the reasons for which they were thought to be useful became apparent and are as follows: Ivermectin binds to insulin-like growth factor and prevents nuclear transportation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), therefore preventing cell entrance, induces apoptosis, and osmotic cell death and disrupts viral replication. Chloroquine/Hydroxychloroquine blocks the movement of SARS-CoV-2 from early endosomes to lysosomes inside the cell, also, this drug blocks the binding between SARS-CoV-2 and Angiotensin-Converting Enzyme (ACE)-2 inhibiting the interaction between the virus spike proteins and the cell membrane and this drug can also inhibit SARS-CoV-2 viral replication causing, ultimately, the reduction in viral infection as well as the potential to progression for a higher severity phenotype culminating with a higher chance of death. Azithromycin exerts a down-regulating effect on the inflammatory cascade, attenuating the excessive production of cytokines and inducing phagocytic activity, and acts interfering with the viral replication cycle. Ivermectin, when compared to standard care or placebo, did not reduce the disease severity, need for mechanical ventilation, need for intensive care unit, or in-hospital mortality. Only one study demonstrated that Ivermectin may improve viral clearance compared to placebo. Individuals who received Chloroquine/Hydroxychloroquine did not present a lower incidence of death, improved clinical status, or higher chance of respiratory deterioration compared to those who received usual care or placebo. Also, some studies demonstrated that Chloroquine/Hydroxychloroquine resulted in worse outcomes and side-effects included severe ones. Adding Azithromycin to a standard of care did not result in clinical improvement in hospitalized COVID-19 participants. In brief, COVID-19 was one of the deadliest pandemics in modern human history. Due to the potential health catastrophe caused by SARS-CoV-2, a global effort was made to evaluate treatments for COVID-19 to attenuate its impact on the human species. Unfortunately, several countries prematurely justified the emergency use of drugs that showed only in vitro effects against SARS-CoV-2, with a dearth of evidence supporting efficacy in humans. In this context, we reviewed the mechanisms of several drugs proposed to treat COVID-19, including Ivermectin, Chloroquine/Hydroxychloroquine, and Azithromycin, as well as the phase III clinical trials that evaluated the efficacy of these drugs for treating patients with this respiratory disease. Conclusions: As the main finding, although Ivermectin, Chloroquine/Hydroxychloroquine, and Azithromycin might have mechanistic effects against SARS-CoV-2 infection, most phase III clinical trials observed no treatment benefit in patients with COVID-19, underscoring the need for robust phase III clinical trials. Full article

This review discusses the pathophysiology of diabetes in pregnancy in relation to the placental function. We review the potential use of hydroxychloroquine in improving pregnancy outcomes affected by diabetes. The review focuses on the mechanism of action of hydroxychloroquine and its potential effects on diabetes. There are several pathways in which hydroxychloroquine mediates its effects: through the inflammasome complex, inflammatory cytokines, oxidative stress, modulatory effects, and antihyperglycemic effects. As a safe drug to be used in pregnancy, it is worth exploring the possible use hydroxychloroquine as an adjunct treatment to the current therapy of diabetes in pregnancy. Full article

Background: Lichen planopilaris (LPP) is an inflammatory cicatricial alopecia characterized by an irreversible destruction of the hair follicle resulting in its permeant destruction. The clinical presentation of LPP is a progressive patchy scarring alopecia. A variety of systemic agents is used to treat LPP with varying success. The aim of this retrospective, real-life analysis was to evaluate the treatment of hydroxychloroquine for LPP. Method: In this retrospective, single-center study, we analyzed 110 patients with LPP and frontal fibrosing alopecia (FFA) who received treatment over a 12-month period from March 2014 to March 2021 at the Department of Dermatology, University of Mainz Medical Center. Patient records were analyzed for response to treatment, co-morbidities, disease progression-free survival (DPFS), and safety. Clinical parameters associated with treatment response were determined with Cox regression modelling and logistic regression. Results: Overall, 77 of 110 patients were treated with a systemic agent. There was a clear association between LPP and the occurrence of Hashimoto thyroiditis. Topical treatment with corticosteroids did not improve clinical symptoms in the majority of patients (15 out of 101). In 71% of patients treated with systemic cyclosporine A and 62% of patients treated with hydroxychloroquine, we observed a significant resolution of the inflammatory process, which correlated with a robust durable clinical response (p < 0.001). Toxicity was observed in 17% (n = 9) of patients receiving systemic treatment with hydroxychloroquine and correlated with the duration of systemic treatment (p < 0.001). Treatment discontinuation was associated with a flare-up of clinical symptoms (29%), which required the re-initiation of second-line therapy in 13 out of 51 patients. Overall, the initiation of second-line treatment, either hydroxychloroquine or Cyclosporine A (CsA), yielded positive results, especially in the patient cohort treated with hydroxychloroquine (overall response rate, ORR = 100%), who showed disease progression during CsA or retinoids. Conclusions: Our results from this contemporary cohort of patients with LPP and FFA indicate that hydroxychloroquine and cyclosporine are effective systemic agents in decreasing clinical symptoms. However, our data also show that the discontinuation of treatment is often associated with the exacerbation of clinical symptoms. Response rates to second-line treatment were especially favorable in the patient cohort with hydroxychloroquine. Full article

Establishing universal standards for the nomenclature and classification of hydroxychloroquine retinopathy is essential. This review summarizes the classifications used for categorizing the patterns of hydroxychloroquine retinopathy and grading its severity in the literature, highlighting the limitations of these classifications based on recent findings. To overcome these limitations, I propose categorizing hydroxychloroquine retinopathy into four categories based on optical coherence tomography (OCT) findings: parafoveal (parafoveal damage only), pericentral (pericentral damage only), combined parafoveal and pericentral (both parafoveal and pericentral damage), and posterior polar (widespread damage over parafoveal, pericentral, and more peripheral areas), with or without foveal involvement. Alternatively, eyes can be categorized simply into parafoveal and pericentral retinopathy based on the most dominant area of damage, rather than the topographic distribution of overall retinal damage. Furthermore, I suggest a five-stage modified version of the current three-stage grading system of disease severity based on fundus autofluorescence (FAF) as follows: 0, no hyperautofluorescence (normal); 1, localized parafoveal or pericentral hyperautofluorescence on FAF; 2, hyperautofluorescence extending greater than 180° around the fovea; 3, combined retinal pigment epithelium (RPE) defects (hypoautofluorescence on FAF) without foveal involvement; and 4, fovea-involving hypoautofluorescence. These classification systems can better address the topographic characteristics of hydroxychloroquine retinopathy using disease patterns and assess the risk of vision-threatening retinopathy by stage, particularly with foveal involvement. Full article

Refractory recurrent pericarditis is a troublesome condition that severely impairs the quality of life of affected patients and significantly increases healthcare spending. Until recently, therapeutic options included only a few medications and most of the patients resorted to chronic glucocorticoid treatment with steroid dependence. In the most recent decade, the introduction of interleukin-1 blockers in clinical practice has revolutionized the treatment of glucocorticoid-dependent and colchicine-resistant recurrent pericarditis due to their excellent efficacy and good safety profile. The rationale for the introduction of this class of medications in clinical practice is the autoinflammatory nature of recurrent pericarditis in a substantial rate of cases, with interleukin-1 being the main pro-inflammatory cytokine involved in this context. This review aims to discuss the contemporary available evidence from original research and real-world data on interleukin-1 blocker use in refractory recurrent pericarditis, in terms of indications, mechanism of action, efficacy, side effects, and recommended treatment protocols. Moreover, novel treatment proposals, such as hydroxychloroquine, beta blockers, and cannabidiol, which showed encouraging preliminary results, are addressed. Finally, gaps in knowledge, unmet needs, and future perspectives related to recurrent pericarditis are thoroughly discussed. Full article