-
Nanomedicine (London, England) Jul 2024This study focused on developing a topical gel incorporating lornoxicam-loaded poly(lactic-co-glycolic acid) and polyethylene glycol (PLGA-PEG) blend nanoparticles to...
This study focused on developing a topical gel incorporating lornoxicam-loaded poly(lactic-co-glycolic acid) and polyethylene glycol (PLGA-PEG) blend nanoparticles to mitigate gastrointestinal (GIT) side effects and enhance therapeutic efficacy. Synthesized nanoparticles were subjected to characterization, permeation studies, and acute oral toxicity analysis post-incorporation into the gel using a S/O/W double emulsion solvent. The nanoparticles displayed a smooth, spherical morphology (170-321 nm) with increased entrapment efficiency (96.2%). LOX exhibited a permeation rate of 70-94% from the nanoparticle-infused gel, demonstrating favorable biocompatibility at the cellular level. The formulated gel, enriched with nanoparticles, holds promising prospects for drug-delivery systems and promising improved therapeutic outcomes for LOX.
PubMed: 38953843
DOI: 10.1080/17435889.2024.2359356 -
Ugeskrift For Laeger Jun 2024This case report describes laryngeal oedema occurring in a 35-year-old woman with chronic bowel-associated dermatosis-arthritis syndrome, and stenosis of the left main...
This case report describes laryngeal oedema occurring in a 35-year-old woman with chronic bowel-associated dermatosis-arthritis syndrome, and stenosis of the left main bronchus. The oedema was attributed to persistent cough exacerbated by delayed treatment and intubation-related irritation. Evaluations ruled out inflammatory, autoimmune, and malignant causes. Literature lacks on specific descriptions of cough-induced laryngeal oedema, emphasizing the need for a multidisciplinary approach and early intervention in complex cases to prevent severe hospitalizations in patients with known serious conditions and symptom exacerbation.
Topics: Humans; Adult; Female; Cough; Laryngeal Edema; Respiration, Artificial; Intubation, Intratracheal
PubMed: 38953687
DOI: 10.61409/V12230792 -
MBio Jul 2024Barmah Forest virus (BFV) is a mosquito-borne virus that causes arthralgia with accompanying rash, fever, and myalgia in humans. The virus is mainly found in Australia...
Barmah Forest virus (BFV) is a mosquito-borne virus that causes arthralgia with accompanying rash, fever, and myalgia in humans. The virus is mainly found in Australia and has caused outbreaks associated with significant health concerns. As the sole representative of the Barmah Forest complex within the genus , BFV is not closely related genetically to other alphaviruses. Notably, basic knowledge of BFV molecular virology has not been well studied due to a lack of critical investigative tools such as an infectious clone. Here we describe the construction of an infectious BFV cDNA clone based on Genbank sequence and demonstrate that the clone-derived virus has and properties similar to naturally occurring virus, BFV field isolate 2193 (BFV2193-FI). A substitution in nsP4, V1911D, which was identified in the Genbank reference sequence, was found to inhibit virus rescue and replication. T1325P substitution in nsP2 selected during virus passaging was shown to be an adaptive mutation, compensating for the inhibitory effect of nsP4-V1911D. The two mutations were associated with changes in viral non-structural polyprotein processing and type I interferon (IFN) induction. Interestingly, a nuclear localization signal, active in mammalian but not mosquito cells, was identified in nsP3. A point mutation abolishing nsP3 nuclear localization attenuated BFV replication. This effect was more prominent in the presence of type I interferon signaling, suggesting nsP3 nuclear localization might be associated with IFN antagonism. Furthermore, abolishing nsP3 nuclear localization reduced virus replication in mice but did not significantly affect disease.IMPORTANCEBarmah Forest virus (BFV) is Australia's second most prevalent arbovirus, with approximately 1,000 cases reported annually. The clinical symptoms of BFV infection include rash, polyarthritis, arthralgia, and myalgia. As BFV is not closely related to other pathogenic alphaviruses or well-studied model viruses, our understanding of its molecular virology and mechanisms of pathogenesis is limited. There is also a lack of molecular tools essential for corresponding studies. Here we describe the construction of an infectious clone of BFV, variants harboring point mutations, and sequences encoding marker protein. In infected mammalian cells, nsP3 of BFV was located in the nuclei. This finding extends our understanding of the diverse mechanisms used by alphavirus replicase proteins to interact with host cells. Our novel observations highlight the complex synergy through which the viral replication machinery evolves to correct mutation errors within the viral genome.
PubMed: 38953633
DOI: 10.1128/mbio.00993-24 -
Frontiers in Immunology 2024
Topics: Humans; Allergy and Immunology; Animals; Microbiology
PubMed: 38953029
DOI: 10.3389/fimmu.2024.1436631 -
Journal of Pain Research 2024Joint pain is one of the most commonly reported pain types in the United States. In the case of patients suffering from inflammatory diseases such as osteoarthritis (OA)...
PURPOSE
Joint pain is one of the most commonly reported pain types in the United States. In the case of patients suffering from inflammatory diseases such as osteoarthritis (OA) and gout, persistent inflammation due to long-term overexpression of several key cytokines has been linked to neuronal hypersensitivity and damage within the joints. Ultimately, a subset of patients develop chronic pain. Pharmacologic treatment of joint pain involves the use of analgesics such as acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs), opioids, antidepressants, as well as intra-articular injections of corticosteroids and hyaluronic acid. However, NSAIDs are short-acting and fail to alleviate severe pain, opioids are generally ineffective at managing chronic pain, and all therapeutic options involve increased risks of serious side effects.
METHODS
We explored the therapeutic and analgesic effects of transforming growth factor-β-activated kinase 1 (TAK1) inhibition in both the monoiodoacetate (MIA) and monosodium urate (MSU) models of joint pain as an innovative strategy for alleviating chronic inflammatory pain. Mechanical allodynia (Von Frey), weight-bearing and histological changes were measured in separate groups of rats receiving either the selective TAK1 inhibitor, HS-276, gabapentin or vehicle.
RESULTS
Our data support that TAK1 inhibition effectively prevented the development of mechanical allodynia and differential weight-bearing in the MIA model. In the MSU model of gouty arthritis, treatment with HS-276 significantly reduced mechanical allodynia and knee edema in female rats, but not male rats. Histological evaluation of effected joints in both models showed that HS-276 treatment significantly reduced disease-induced degradation of the joint.
CONCLUSION
Our results support that TAK1 is a critical signaling node in inflammatory joint diseases such as OA and gouty arthritis. Selective pharmacological inhibition significantly attenuated several aspects of the disease, including joint degeneration and mechanical pain. Thus, TAK1 is a novel therapeutic target for the treatment of painful inflammatory joint diseases.
PERSPECTIVE
This article reports on the therapeutic potential of TAK1 in the treatment of chronic inflammatory joint diseases such as OA and gout. Using the selective TAK1 inhibitor, HS-276, we show the therapeutic and analgesic effects of TAK1 inhibition in two preclinical murine models of inflammatory joint pain.
PubMed: 38952995
DOI: 10.2147/JPR.S451409 -
Upadacitinib for the treatment of psoriasiform and spongiotic dermatitis: A multicenter case series.JAAD Case Reports Jul 2024
PubMed: 38952860
DOI: 10.1016/j.jdcr.2024.05.009 -
Sudanese Journal of Paediatrics 2024Sarcoidosis is a chronic multisystem granulomatous disease of unknown etiology. It is rare in young children. A 9-year-old boy presented with failure to thrive, skin...
Sarcoidosis is a chronic multisystem granulomatous disease of unknown etiology. It is rare in young children. A 9-year-old boy presented with failure to thrive, skin rashes, persistent fever, and respiratory symptoms since 5 years of age. Blood investigations done showed elevated serum calcium and angiotensin converting enzyme levels and biopsy of the rashes on the left shin revealed non-caseating granulomatous lesion. Computed tomography of chest revealed interstitial lung disease and examination of eyes showed bilateral uveitis. He also had sensorineural hearing impairment, nephrocalcinosis, and short stature. The patient was treated with oral steroids and mycophenolate mofetil. At follow up, there was improvement in his systemic features including rashes and arthritis. Early detection, diagnosis, and appropriate treatment of sarcoidosis are vital for disease control and to avoid morbidity.
PubMed: 38952623
DOI: 10.24911/SJP.106-1681705847 -
Clinical Case Reports Jul 2024Clinicians should carefully consider generalized lymphadenopathy, particularly post viral infections, as one of the possible systemic lupus erythematous (SLE) first...
KEY CLINICAL MESSAGE
Clinicians should carefully consider generalized lymphadenopathy, particularly post viral infections, as one of the possible systemic lupus erythematous (SLE) first signs regarding unusual joint involvements such as sacroiliitis. Late diagnosis of this autoimmune inflammatory disease, could lead to irreversible morbidity and higher mortality.
ABSTRACT
Lymphadenopathy could represent various etiologies, including infections, malignancies, and rheumatologic diseases. SLE is known as the great mimicker which could be presented with different first manifestations. We report a 42-year-old woman in the acute phase of Epstein-Barr infection, admitted with polyarticular peripheral arthritis, sacroiliitis, and generalized lymphadenopathy. She had no similar history or taken unpasteurized dairy. Nodes were soft, mobile, and tender without skin change on top. During the process, she was diagnosed with SLE and discharged with prednisolone 30 mg/day and hydroxychloroquine 400 mg/day. After 2 weeks of follow-up, all lymphadenopathy and symptoms were diminished. This case underscores the thousand faces innate of SLE. Clinical awareness would lead to an accurate diagnosis and early intervention.
PubMed: 38952465
DOI: 10.1002/ccr3.9134 -
Journal of Materials Chemistry. B Jul 2024Europium ions (Eu) are gaining attention in the field of regenerative medicine due to increasing evidence of their osteogenic properties. However, inflammatory and...
Europium ions (Eu) are gaining attention in the field of regenerative medicine due to increasing evidence of their osteogenic properties. However, inflammatory and oxidative environments present in many bone diseases, such as osteoporosis or rheumatoid arthritis, are known to hinder this regenerative process. Herein, we describe a straightforward synthetic procedure to prepare Eu-tannic acid nanocomplexes (EuTA NCs) with modulable physicochemical characteristics, as well as antioxidant, anti-inflammatory, and osteogenic properties. EuTA NCs were rationally synthesized to present different contents of Eu on their structure to evaluate the effect of the cation on the biological properties of the formulations. In all the cases, EuTA NCs were stable in distilled water at physiological pH, had a highly negative surface charge ( ≈ -25.4 mV), and controllable size (80 < < 160 nm). antioxidant tests revealed that Eu complexation did not significantly alter the total radical scavenging activity (RSA) of TA but enhanced its ability to scavenge HO and ferrous ions, thus improving its overall antioxidant potential. At the cellular level, EuTA NCs reduced the instantaneous toxicity of high concentrations of free TA, resulting in better antioxidant (13.3% increase of RSA TA) and anti-inflammatory responses (17.6% reduction of nitric oxide production TA) on cultures of HO- and LPS-stimulated macrophages, respectively. Furthermore, the short-term treatment of osteoblasts with EuTA NCs was found to increase their alkaline phosphatase activity and their matrix mineralization capacity. Overall, this simple and tunable platform is a potential candidate to promote bone growth in complex environments by simultaneously targeting multiple pathophysiological mechanisms of disease.
PubMed: 38952270
DOI: 10.1039/d4tb00697f -
Current Rheumatology Reviews Jun 2024Clinically relevant fatigue in rheumatoid arthritis (RA) patients significantly affects their quality of life. Almost all studies have assessed fatigue in this...
BACKGROUND
Clinically relevant fatigue in rheumatoid arthritis (RA) patients significantly affects their quality of life. Almost all studies have assessed fatigue in this population using non-specific scales. The present multi-centric study aimed to assess the validity, reliability, and clinical significance of the Arabic version of the Bristol Rheumatoid Arthritis Fatigue Multi-Dimensional Questionnaire (BRAF-MDQ).
METHODS
The present cross-sectional multicentric study was conducted at Aswan, Mansoura, Port Said, and Al-Azhar University Hospitals over a 6-month duration. The study included 311 patients with RA diagnosed according to the 2010 criteria of the American College of Rheumatology. The Arabic version of BRAF-MDQ was developed to assess fatigue in these patients. All patients were subjected to careful history taking, thorough clinical assessment, and standard laboratory work-up. The obtained Arabic BRAF-MDQ was tested for construct validity, internal consistency, testretest reproducibility, and criterion validity. Construct validity was evaluated using factor analysis with the Kaiser Meyer Olkin tool of sampling adequacy and Bartlett's sphericity test. Internal consistency of subscales was assessed using Cronbach's alpha. Test-retest reproducibility was assessed after a 1-week interval using the intraclass correlation coefficient. Pearson's correlation coefficient was used to correlate numerical variables. Predictors of fatigue were identified using binary logistic regression analysis.
RESULTS
The present study included 311 RA patients. Construct validity assessment showed a high loading of questionnaire items within the proposed construct subscales with a KMO measure of sphericity of 0.927 and Bartlett's test of sphericity p-value < 0.001. Internal consistency assessment showed adequate Cronbach's alpha of Arabic BRAF-MDQ subscales. Total Arabic BRAFMDQ had excellent criterion validity, as indicated by the high correlations with MAFS (r=0.95, p < 0.001) and SF-36 vitality subscale (r=-0.91, p < 0.001). Clinically significant fatigue was identified in 214 patients (68.8%). Multivariate logistic regression analysis revealed age (OR (95% CI): 1.07 (1.02-1.12), p < 0.001), disease duration (OR (95% CI): 1.82 (1.43-2.33), p < 0.001), DAS28CRP (OR (95% CI): 8.62 (4.63-16.02), p < 0.001), and mHAQ (OR (95% CI): 3.85 (1.07-13.9), p = 0 .039) as significant predictors of fatigue development in the studied patients.
CONCLUSION
The Arabic version of the Bristol Rheumatoid Arthritis Fatigue Multi-Dimensional Questionnaire is a valid, consistent, and reliable tool for the assessment of fatigue in Egyptian rheumatoid arthritis patients. Clinically significant fatigue was identified in 214 patients (68.8%). Further, risk factors for fatigue included older age, longer disease duration, and higher disease activity.
PubMed: 38952155
DOI: 10.2174/0115733971292438240620064231