Gingerol nanoparticles attenuate complete Freund adjuvant-induced arthritis in rats via targeting the RANKL/OPG signaling pathway.

Rheumatoid arthritis (RA) is characterized by inflammatory joint pathology leading to the degradation of articular bone and cartilage, primarily triggered by synovial inflammation, resulting in joint discomfort. The metacarpophalangeal and proximal interphalangeal joints are predominantly affected. Treatment typically involves a combination of biological and synthetic disease-modifying antirheumatic drugs (DAMARDs) alongside steroid therapy. The application of nanomedicine has been instrumental in enhancing treatment efficacy by facilitating controlled release of pharmacologically active compounds, thus augmenting bioavailability and enabling targeted drug delivery. Gingerol, a constituent of ginger, possesses multifaceted properties. including anti-inflammatory, anti-oxidant, antidiabetic, and antipyretic effects. In this study, gingerol-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs), coated with chitosan, were administered orally to rats over a period of 21 days to address RA induced by complete Freund adjuvant (CFA). The rats were segregated into four experimental groups. Upon completion of the treatment regimen, blood samples were collected for the assessment of cyclooxygenase-2 (COX-2), RA factor, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α). Subsequent gene expression analysis was conducted to evaluate the levels of interleukin-4 (IL-4), interleukin-17a (IL-17a), IL-6, interferon-gamma (INF-γ), TNF-α, interleukin-1 beta (IL-1ß), osteoprotegerin (OPG), and receptor activator of nuclear factor kappa-B ligand (RANKL). Statistical analyses utilizing one-way ANOVA followed by Tukey tests were applied to the data. The gene expression profiling revealed significant disparities in mRNA levels of IL-1ß, IL-6, IL-4, IL-17a, RANKL, INF-γ, and TNF-α between the CFA-induced arthritis group and the control group. Consequently, it was inferred that gingerol-loaded PLGA NPs coated with chitosan exhibited heightened therapeutic efficacy in addressing CFA-induced arthritis in rats.

Paraneoplastic musculoskeletal disorders: review and update for radiologists.

Rheumatic paraneoplastic syndromes are rare syndromes that occur at distant sites from the underlying tumor and may involve the bones, joints, fasciae, muscles, or vessels. In the absence of a known tumor, early recognition of a rheumatic syndrome as paraneoplastic permits dedicated work-up for, and potentially early treatment of an occult malignancy. Although there is a continuously growing list of paraneoplastic rheumatic disorders, not all of these disorders have a well-established association with a neoplastic process. The goals of this article are to review the clinical characteristics, diagnostic work-up, and imaging findings of well-documented rheumatic paraneoplastic disorders.

Aqua-Plyometric Exercises-Induced Changes in Muscle Strength, Bone Mineral Properties, and Physical Fitness in Patients With Juvenile Idiopathic Arthritis: A 12-Week, Randomized Controlled Trial.

PURPOSE: To determine whether a 12-week, lower body-targeted aqua-plyometric (AquaPlyo) exercise program could improve muscle strength, bone mineral properties, and physical fitness in patients with juvenile idiopathic arthritis. METHODS: A randomized controlled trial was adopted and included 48 patients with polyarticular juvenile idiopathic arthritis (age: 12-18 y). Patients were assigned to undergo either AquaPlyo exercises (AquaPlyo group, n = 24) or standard exercises (control group, n = 24). The outcome measures were assessed pretreatment and posttreatment and included concentric quadriceps peak torque, bone mineral properties (areal bone mineral density [BMD], volumetric BMD, bone mineral content, and BMD Z score), and physical fitness. RESULTS: A significant posttreatment increase in the concentric quadriceps peak torque was detected in the AquaPlyo group compared with the control group (either at an angular velocity of 90°/s [right side: P = .016, left side: P = .025] or 180°/s [right side: P = .007, left side: P = .029]). Besides, a considerably greater improvement in the areal BMD (P = .0006), volumetric BMD (P = .027), bone mineral content (P = .002), and BMD Z score (P = .0004) was observed in the AquaPlyo group. Moreover, a remarkably greater rise in the physical fitness (P < .001) was revealed in the AquaPlyo group. CONCLUSION: AquaPlyo training can efficiently enhance muscle strength, improve bone mineral properties, and boost physical fitness in patients with juvenile idiopathic arthritis.

Associations of inflammatory polyarthritis with clinical and radiological findings of temporomandibular disorders.

OBJECTIVE: To evaluate the association of different forms of inflammatory polyarthritis with clinical signs of temporomandibular disorders (TMD) and radiological findings in temporomandibular joint (TMJ), based on a nationwide health survey in Finland. The aim was also to assess the presence of clinical and radiological TMD findings in subjects with increased risk for developing rheumatoid arthritis (RA). MATERIAL AND METHODS: A nationally representative sample included 6331 Finnish adults who participated in the Health 2000 Survey (BRIF8901). Subjects were examined for signs of TMD, findings in panoramic radiograph of TMJ, musculoskeletal health and serology (rheumatoid factor, RF, and anti-cyclic citrullinated peptide, aCCP). RESULTS: Sixty-four percent of seronegative RA and 60% of seropositive RA subjects had at least one sign of TMD. While adjusting for confounding factors (gender, age, dentures and smoking history), RA was significantly associated with crepitation and abnormal radiological findings in TMJ. Seronegative RA was also associated with restricted mouth opening. Systemic autoimmunity associated with RA ("at risk of RA") was not associated with clinical or radiological TMD findings. CONCLUSIONS: Clinical and radiological findings of TMD are more prevalent among subjects with inflammatory polyarthritis than among the population in general in the Finnish adult population.

Rheumatoid factor value for determining the first biologic agent to use for non-systemic juvenile idiopathic arthritis.

OBJECTIVES: Currently, no indicators on which biologic disease-modifying anti-rheumatic drugs (bDMARDs) should be used first for juvenile idiopathic arthritis (JIA) have been established. Thus, this study aimed to determine the useful biomarkers in JIA to enable the best selection of the first bDMARDs without primary failure. METHODS: This retrospective study used data of patients examined for JIA between 2015 and 2021 at Kagoshima University Hospital in Japan. RESULTS: Altogether, 67 cases of non-systemic JIA were analyzed, excluding cases that had been treated for <6 months. Of the 67 cases, 52 were treated with bDMARDs and all rheumatoid factor (RF)+ types (32 cases) were treated with bDMARDs. Eleven cases (31.4&) (all were RF+ types and used anti-tumor necrosis factor (TNF)α agents) switched to other bDMARDs because of primary failure, and nine cases had secondary failure (6;anti-TNF, 3;anti-Interleukin-6). A significant difference in pre-treatment RF values (177.9 vs 25.7 IU/ml, p = 0.002) and presence (Odds Ratio 1.952,p = 0.004) were observed between the primary failure group and effective group. CONCLUSIONS: RF+ JIA required bDMARDs with high probability. JIA with high titre of RF tends to be refractory to anti-TNFα agents. Tocilizumab or abatacept could be a first-choice bDMARD in such cases.

A Case of Mycoplasma Infection with an Atypical Presentation of Abducens Nerve Palsy, Erythema Multiforme and Polyarthritis without Respiratory Manifestations.

Mycoplasma pneumoniae is a self-propagating microorganism that commonly causes respiratory tract infections. It can also cause a variety of extrapulmonary symptoms with or independently of respiratory symptoms, such as skin lesions, arthralgia, myalgia, hemolysis, cardiac lesions, gastrointestinal symptoms, and central nervous system lesions, which are rare manifestations reported in approximately 0.1% of cases. In this study, we present a unique case of Mycoplasma-related abducens nerve palsy, polyarthritis, and erythema multiforme without respiratory disease. The patient was a 69-year-old woman who presented to our hospital with a skin rash, fever, arthralgia, and diplopia without respiratory symptoms. Brain magnetic resonance imaging showed optic neuritis on the right side, suggesting the diplopia was caused by right abducens nerve palsy. However, the etiologies of abducens nerve palsy were not revealed by the physical examination, blood biochemistry tests, or bacteriological examinations, including the cerebrospinal fluid examination obtained at admission. Mycoplasma infection was suspected from erythema multiforme revealed by a skin biopsy and polyarthralgia, and it was finally diagnosed according to elevated Mycoplasma particle agglutination (PA) antibodies in paired serum. Though minocycline did not improve her diplopia, the daily administration of 30 mg of prednisolone gradually improved her symptoms, and the Mycoplasma PA antibody titer, which was regularly measured in the clinical course, also decreased, suggesting a relationship between Mycoplasma infection and abducens nerve palsy. This is the first case of isolated abducens nerve palsy, which was reported as the only central neurological symptom in an adult patient with Mycoplasma infection. The mechanism or pathogenesis of CNS manifestations caused by Mycoplasma pneumoniae remains to be elucidated, and further investigation is needed. Hence, Mycoplasma infection is a common disease. Clinicians should be aware of the diverse manifestations, including abducens nerve palsy, of Mycoplasma infection and should consider Mycoplasma infection even in the absence of typical respiratory symptoms.

Bilateral Cubital Lymphoma and Mycobacteriosis in a Salmon-Crested Cockatoo (Cacatua moluccensis).

A 32-year-old male salmon-crested cockatoo (Cacatua moluccensis) was diagnosed by cytology with bilateral cubital lymphoma and mycobacteriosis. Polymerase chain reaction assay testing confirmed Mycobacterium genavense. This patient was subsequently humanely euthanized. Postmortem histopathology confirmed both diagnoses with findings of multicentric lymphoma, acid-fast bacilli, and severe degenerative changes in all synovial joints examined. Immunohistochemical staining for paired box protein 5 of the cubital mass was positive for a high percentage of B-cell lymphocytes, consistent with B-cell lymphoma. This unusual case of two major diseases presenting concurrently in one patient raises the question of whether the pathogenesis could have an interdependent relationship. Mycobacteriosis, severe degenerative joint changes, or both may have stimulated lymphocytes, eventually leading to lymphoma. Additional screening and monitoring for comorbidities may be advised if 1 of these diseases are diagnosed in companion avian species.

11ß-Hydroxysteroid Dehydrogenase Type 1 within Osteoclasts Mediates the Bone Protective Properties of Therapeutic Corticosteroids in Chronic Inflammation.

Therapeutic glucocorticoids (GCs) are powerful anti-inflammatory tools in the management of chronic inflammatory diseases such as rheumatoid arthritis (RA). However, their actions on bone in this context are complex. The enzyme 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) is a mediator of the anti-inflammatory actions of therapeutic glucocorticoids (GCs) in vivo. In this study we delineate the role of 11ß-HSD1 in the effects of GC on bone during inflammatory polyarthritis. Its function was assessed in bone biopsies from patients with RA and osteoarthritis, and in primary osteoblasts and osteoclasts. Bone metabolism was assessed in the TNF-tg model of polyarthritis treated with oral GC (corticosterone), in animals with global (TNF-tg11ßKO), mesenchymal (including osteoblast) (TNF-tg11ßflx/tw2cre) and myeloid (including osteoclast) (TNF-tg11ßflx/LysMcre) deletion. Bone parameters were assessed by micro-CT, static histomorphometry and serum metabolism markers. We observed a marked increase in 11ß-HSD1 activity in bone in RA relative to osteoarthritis bone, whilst the pro-inflammatory cytokine TNFα upregulated 11ß-HSD1 within osteoblasts and osteoclasts. In osteoclasts, 11ß-HSD1 mediated the suppression of bone resorption by GCs. Whilst corticosterone prevented the inflammatory loss of trabecular bone in TNF-tg animals, counterparts with global deletion of 11ß-HSD1 were resistant to these protective actions, characterised by increased osteoclastic bone resorption. Targeted deletion of 11ß-HSD1 within osteoclasts and myeloid derived cells partially reproduced the GC resistant phenotype. These data reveal the critical role of 11ß-HSD1 within bone and osteoclasts in mediating the suppression of inflammatory bone loss in response to therapeutic GCs in chronic inflammatory disease.

[Polyarticular juvenile idiopathic arthritis and rheumatoid arthritis : Common features and differences]. / Polyartikuläre juvenile idiopathische Arthritis und rheumatoide Arthritis : Gemeinsamkeiten und Unterschiede.

The spectrum of polyarthritic diseases in childhood as well as in adulthood is wide. In the differential diagnostics different age-related diseases must be taken into consideration. Although, a clear similarity is obvious in all age groups for the classical diseases of polyarticular juvenile idiopathic arthritis and rheumatoid arthritis with respect to the pathogenesis, clinical manifestation and treatment options, this review points to specific differences. The prognosis of polyarthritis in children mainly depends on the joint manifestation, whereas extra-articular comorbidities play a predominant role in the older adult population.

Mycoplasma bovis-pneumonia and polyarthritis in feedlot calves in Argentina: First local isolation.

Bovine respiratory disease (BRD) is one of the most frequent clinical concerns in weaned calves after their arrival at the feedlot. This work reports the first local isolation of Mycoplasma bovis from feedlot calves with pneumonia and polyarthritis in Argentina. Twenty four out of 545 calves showed progressive, subacute to chronic respiratory distress, coughing, and fever. Thirty percent of the affected calves also showed lameness and swelling of elbow or carpal, and knee or tarsal joints. Five necropsies were performed and severe multifocal to coalescent pulmonary nodules, containing white-yellowish caseous exudate encircled by fibrous tissue, and fibrinonecrotic arthritis and tenosynovitis were detected. Mycoplasma was isolated from lung and joint samples. The 16S-23S rRNA ITS consensus sequence obtained from these isolates showed 100% similarity with the same region of M. bovis strains. Since there are no commercially available vaccines in the region for the prevention and control of M. bovis pneumonia and arthritis, surveillance is a priority to reduce the source of disease to naïve animals.

Septic Polyarthritis Caused by Streptobacillus moniliformis.

Streptobacillus moniliformis is a pleomorphic, fastidious gram-negative bacillus that colonizes rodent respiratory tracts and causes rat-bite fever in humans. Rat-bite fever is associated with septic arthritis, usually monoarticular or pauciarticular. We report a rare case of polyarticular septic arthritis caused by S. moniliformis; the disease was initially misdiagnosed as inflammatory arthritis.

Chemical characterization and anti-arthritic appraisal of Monotheca buxifolia methanolic extract in Complete Freund's Adjuvant-induced arthritis in Wistar rats.

The current study was designed to evaluate the anti-oxidant and anti-arthritic potential of a traditionally used herb, Monotheca buxifolia. The M. buxifolia methanolic extract (MBME) was prepared from the aerial parts of the plant followed by chemical characterization with GC-MS. The anti-oxidant potential of the MBME was demonstrated by DPPH scavenging activity. The effects of MBME on protein denaturation and membrane stabilization were determined by inhibition of egg albumin denaturation and RBC membrane stabilization assays, respectively. The in vivo anti-arthritic potential of the MBME at 50, 100, and 150 mg/kg/day was evaluated in Complete Freund's Adjuvant-induced polyarthritis in Wistar rats treated for 21 days. Phytochemicals, such as linolenic acid methyl ester, n-hexadecanoic acid, vitamin E, α-amyrin, and ß-amyrin were detected in the GC-MS analysis. The plant extract exhibited a 55.20 ± 0.69% scavenging of free radicals at 100 µg/ml concentration. It significantly (p < 0.05) stabilized human RBC membrane (65.06 ± 0.22%) and inhibited protein denaturation (70.53 ± 0.34%) at 100 mg/ml concentration. The diclofenac sodium (DS) and MBME at 150,100, and 50 mg/kg reduced the paw edema, restored the body weight, and altered blood parameters including CRP. The MBME significantly reduced the MDA and increased the SOD, CAT, and GSH levels in liver tissue homogenate in treated rats. The serum concentration of TNF-α and PGE2 was remarkably (p < 0.01-< 0.0001) restored by the DS and MBME dose dependently. The histopathological study showed that MBME 150 mg/kg commendably restored the ankle joint inflammation, bone erosion, and cartilage damage in polyarthritic rats. It was concluded that the anti-oxidant, anti-inflammatory and anti-arthritic effects of MBME might be attributed to phenols, flavonoids, triterpenoids, vitamin E, phytol, and other fatty acids. This study showed the anti-arthritic potential of Monotheca buxifolia and thus validates its traditional claim.

[A several-week history of inflammatory changes in the right foot and right hand of a 57-year-old male patient]. / Seit mehreren Wochen bestehende entzündliche Veränderungen an rechtem Fuß und rechter Hand bei einem 57-jährigen Patienten.

Metastatic fat necrosis due to inflammatory or neoplastic pancreatic diseases is rare. This phenomenon is attributed to systemic effects of pancreatic enzymes. Depending on the sites of fat necrosis, a number of different diseases may be mimicked, leading to incorrect diagnosis and therapies. Many case reports describe the phenomenon of skin, joint and bone manifestations of fat necrosis under the acronym PPP (pancreatic, panniculits, polyarthritis) syndrome. The management of "autodigestion" primarily consists of treating the underlying pancreatic disease.

Anti-cyclic citrullinated peptide antibody in psoriatic arthritis: a meta-analysis of its frequency and association with clinical features.

OBJECTIVE: This study aimed to investigate the frequency of the anti-cyclic citrullinated peptide (anti-CCP) antibody in patients with psoriatic arthritis (PsA) and to assess its associations with clinical features of this disease. METHODS: The Medline, EMBASE, and Cochrane databases were searched for studies that examined anti-CCP antibodies in patients with PsA. Meta-analyses of the frequency of the anti-CCP antibody in these patients and its association with polyarthritis, bone erosion, dactylitis, and enthesitis were then performed. RESULTS: Fourteen studies with a combined total of 3291 patients with PsA met the inclusion criteria for this meta-analysis. The pooled overall frequency of anti-CCP antibodies was 9.8% (95% confidence interval [CI] = 7.1-13.3, p < 0.001). Stratification by ethnicity showed that the anti-CCP antibody frequency was lower in Europeans than in non-Europeans (8.5% vs. 14.0%). The meta-analysis showed a significant association of the anti-CCP antibody with polyarthritis (odds ratio [OR] = 4.390, 95% CI = 2.312-8.333, p < 0.001), bone erosion (OR = 2.800, 95% CI = 1.921-4.081, p < 0.001), and dactylitis (OR = 1.958, 95% CI = 1.340-2.861, p < 0.001). However, there was no association between this antibody and enthesitis. CONCLUSIONS: Our meta-analysis demonstrated that the overall frequency of the anti-CCP antibody was 9.8% in patients with PsA, and its presence was associated with increased risks of polyarthritis, bone erosion, and dactylitis, but not of enthesitis.

Localized Outbreaks of Epidemic Polyarthritis among Military Personnel Caused by Different Sublineages of Ross River Virus, Northeastern Australia, 2016-2017.

Two outbreaks of epidemic polyarthritis occurred among Australian Defence Force personnel during and following short military exercises in the Shoalwater Bay Training Area, northeastern Australia, in 2016 and 2017. Ross River virus (RRV) IgM was detected in acute-phase serum samples from most patients (28/28 in 2016 and 25/31 in 2017), and RRV was recovered from 4/38 serum samples assayed (1/21 in 2016 and 3/17 in 2017). Phylogenetic analyses of RRV envelope glycoprotein E2 and nonstructural protein nsP3 nucleotide sequences segregated the RRV isolates obtained in 2016 and 2017 outbreaks into 2 distinct sublineages, suggesting that each outbreak was caused by a different strain of RRV. The spatiotemporal characteristics of the 2016 outbreak suggested that some of the infections involved human-mosquito-human transmission without any intermediate host. These outbreaks highlight the importance of personal protective measures in preventing vectorborne diseases for which no vaccine or specific prophylaxis exists.

Epidemiologic, Entomologic, and Virologic Factors of the 2014-15 Ross River Virus Outbreak, Queensland, Australia.

Australia experienced its largest recorded outbreak of Ross River virus (RRV) during the 2014-15 reporting year, comprising >10,000 reported cases. We investigated epidemiologic, entomologic, and virologic factors that potentially contributed to the scale of the outbreak in Queensland, the state with the highest number of notifications (6,371). Spatial analysis of human cases showed that notifications were geographically widespread. In Brisbane, human case notifications and virus detections in mosquitoes occurred across inland and coastal locations. Viral sequence data demonstrated 2 RRV lineages (northeastern genotypes I and II) were circulating, and a new strain containing 3 unique amino acid changes in the envelope 2 protein was identified. Longitudinal mosquito collections demonstrated unusually high relative abundance of Culex annulirostris and Aedes procax mosquitoes, attributable to extensive freshwater larval habitats caused by early and persistent rainfall during the reporting year. Increased prevalence of these mosquitoes probably contributed to the scale of this outbreak.

Acute generalized pustular bacterid concomitant with erythema nodosum, polyarthritis, and Achilles tendinitis.

We report a case of acute generalized pustular bacterid (AGPB) concomitant with erythema nodosum (EN), polyarthritis, and Achilles tendinitis. The patient was admitted with a complaint of fever, widespread plural pustules, erythema, and polyarthralgia. Histopathological examination of the skin lesions demonstrated features of AGBP and EN. Although arthralgia and AGPB can be recognized together, EN and Achilles tendinitis are rare manifestations seen in patients with AGPB. In this case report, we suggest arthralgia, EN, and Achilles tendinitis could coexist with AGPB.

[Options in joint-preserving surgical treatment of osteoarthritis]. / Optionen der gelenkerhaltenden operativen Omarthrosetherapie.

BACKGROUND: The treatment of glenohumeral arthritis represents a major challenge in highly active younger patients. In these patients, an endoprosthetic treatment often achieves only unsatisfactory results with a limited lifetime of the implant. OBJECTIVES: The aim of the study was to identify joint-preserving therapies for glenohumeral arthritis. MATERIALS AND METHODS: For this study, an extensive and selective literature search was performed. RESULTS: There are several options available for joint-preserving treatment of glenohumeral arthritis. In addition to arthroscopic debridement with treatment of concomitant pathologies, CAM procedures (CAM: comprehensive arthroscopic management) according to Millett, as well as the interposition of allografts are other options. For all therapy options, an improved range of motion and pain reduction is described. A joint gap of <2 mm, bipolar cartilage lesions and age are described as risk factors for failure of the therapies. DISCUSSION: Short and mid-term results have been described for arthroscopic debridement, but there are no long-term and high-quality studies to enable us to make clear recommendations. The CAM procedure and the interposition of an allograft are demanding procedures that should be reserved for experienced arthroscopists. The therapies are an option for younger patients in accordance with individual decisions and realistic expectations.

Pancreatic Panniculitis and Polyarthritis.

PURPOSE OF REVIEW: Polyarthritis can have numerous reasons and may thus constitute a challenge for differential diagnosis. One rare potential reason for sterile polyarthritis is underlying pancreatic disease with systemic hyperlipasemia, most often accompanied by painful skin lesions caused by a subcutaneous inflammatory process known as panniculitis. Systematic evidence on pancreatic panniculitis and polyarthritis is limited, particularly regarding its feature as facultative paraneoplasia with underlying intra- or even extra-pancreatic malignancy. Therefore, we will summarize the current knowledge about this orphan disease including epidemiological, pathophysiological, diagnostic, and treatment aspects in the present review. RECENT FINDINGS: Although direct evidence is lacking, it is highly probable that pancreatic polyarthritis and panniculitis are caused by peripheral lipolytic activity of lipase systemically circulating due to benign (e.g., acute or chronic pancreatitis) or malign (e.g., acinar cell carcinoma (ACC) or adenocarcinoma) pancreatic disease. In the latter case, pancreatic polyarthritis and panniculitis are associated with poor outcome. Pancreatic polyarthritis and panniculitis should always be included into diagnostic considerations, and once suspected, a thorough work-up to identify the underlying disease has to be performed.