Navigating the Factors Affecting Functional Impairment in Spondyloarthritis.

Objectives: This study aimed to assess the predictive factors of functional impairment in spondyloarthritis (SpA) patients assessed with bath ankylosing spondylitis functional index (BASFI) and Lequesne Index (LI). Methods: This retrospective study was conducted at the Rheumatology Department of Mohamed Kassab Institute of Orthopedics, Manubah, Tunisia, and collected data from 2008 to 2019 over a period of 4 months (August to November 2019). Socio-demographic and disease-related data of SpA patients were collected. Disease activity was assessed using the bath ankylosing spondylitis-global score (BASG-s) and the bath ankylosing spondylitis disease activity index (BASDAI). The spinal mobility was evaluated by the bath ankylosing spondylitis metrology index (BASMI). Structural progression was evaluated with the bath ankylosing spondylitis radiologic index (BASRI) and modified stoke ankylosing spondylitis spine score (mSASSS). A multivariate analysis was done to search for predictive factors associated with BASFI and LI. Results: A total of 263 patients were included. The mean age was 38.9 ± 12.7 years and the gender ratio was 2.7. The mean age of onset of SpA was 27.6 ± 10.8 years and disease duration was 11.3 ± 9.5 years. Occupation was significantly associated with BASFI and LI scores. A significant functional impact was notably correlated with a long duration of the disease. The two scores were correlated with a limitation of spinal mobility (BASMI), a greater disease activity (BASDAI and erythrocyte sedimentation rate) and a greater impact of the disease on health status (BASG-s). Significant functional impairment was also correlated with structural impairment (mSASSS, BASRI and sacroiliitis grade). The variables independently related to BASFI were the mSASSS score and the BASDAI. The variables independently related to LI were profession (unemployed subjects had higher scores), the mSASSS score and the BASMI. Conclusion: Occupation, disease activity, mobility and structural progression predicted functional impairment in Tunisian SpA patients.

Complications of Paget Bone Disease: A Study of 69 Patients.

INTRODUCTION: Paget bone disease (PBD) is characterized by a disorder in the bone remodeling activity at sites of involvement. This can produce dramatic alterations of local bone architecture and causes most of the complications. We aimed to focus on the characteristics of complications of PDB among hospitalized patients. MATERIAL AND METHODS: A retrospective study was conducted, on PBD patients hospitalized in two rheumatology centers from 1994 to 2019. Characteristics of the PBD complications were studied. RESULTS: Sixty-nine patients were collected with a sex ratio of 0.76 and a mean age of 75.4±6.4 years [43-101]. The diagnosis of PBD was established in the average age of 64.2±11.5 years. The primary reason for consultation was pain (78.3%). The PBD was localized in the pelvis (58%), lower limb (42%), spine (36.2%), skull (23.2%) and upper limb (5.8%). It was polyostotic in 44.9% of cases. Dosage of ALP was 324 [68-8390]. The PDB complication rate was 52.2% and it decreased over time. The main complication was osteoarthritis (23.2%), followed by deafness (17.4%), fracture (15.9%), hydrocephalus (7.2%), neurological disease (7.2%) and osteosarcoma (1.4%). The presence of complications was significantly associated with the polyostotic form (p=0.01), the skull localization (p=0.04), an increased ALP (p=0.02). CONCLUSION: According to our study, the incidence rate of PBD among hospitalized cases is higher among elderly women and decreases over time. Complications related to PDB are frequent (52%). It concerns patients with a polyostotic form, skull localization and high ALP.

Atypical osteomalacia mimicking radiological features of spondyloarthritis: Never judge a book by its cover.

Longstanding osteomalacia, by its proliferative enthesopathic changes, may mimic the advanced features of SpA. Despite the typical radiological findings, the lack of response to anti-TNF should encourage clinicians to reconsider the diagnosis.

Skeletal fluorosis: don't miss the diagnosis!

Skeletal fluorosis is a rare toxic osteopathy characterized by massive bone fixation of fluoride. The disease occurs as an endemic problem in some parts of the world and is the result of prolonged ingestion or rarely by inhalation of high amounts of fluoride. Radiographic presentation is mainly characterized by bone changes with osteocondensation and later ossification of many ligaments and interosseous membranes. Skeletal fluorosis is not clinically obvious and can be confused with other rheumatologic disorders. Its severity lies in the development of skeletal deformities and neurological complications. Management of fluorosis generally focuses on symptom treatment.

Beneficial effects of mycophenolate mofetil on cardiotoxicity induced by tacrolimus in wistar rats.

The immunosuppressive drug tacrolimus (TAC) is used clinically to reduce the rejection rate in transplant patients. TAC has contributed to an increased prevalence of cardiovascular disease in patients receiving solid organ transplantation. Mycophenolate mofetil (MMF), a potent inhibitor of de novo purine synthesis, is known to prevent ongoing rejection in combination with TAC. In the present study, we investigated the antioxidant and antigenotoxic effect of MMF on TAC-induced cardiotoxicity in rats. Oral administration of TAC at 2.4, 24, and 60 mg/kg b.w. corresponding, respectively, to 1, 10, and 25% of LD50 for 24 h caused cardiac toxicity in a dose-dependant manner. TAC increased significantly DNA damage level in hearts of treated rats. Furthermore, it increased malondialdehyde (MDA) and protein carbonyl (PC) levels and decreased catalase (CAT) and superoxide dismutase (SOD) activities. The oral administration of MMF at 50 mg/kg b.w. simultaneously with TAC at 60 mg/kg b.w. proved a significant cardiac protection by decreasing DNA damage, MDA, and PC levels, and by increasing the antioxidant activities of CAT and SOD. Thus, our study showed, for the first time, the protective effect of MMF against cardiac toxicity induced by TAC. This protective effect was mediated via an antioxidant process.

Combination of tacrolimus and mycophenolate mofetil induces oxidative stress and genotoxicity in spleen and bone marrow of Wistar rats.

Tacrolimus (TAC) and mycophenolate mofetil (MMF) are common immunosuppressive drugs used to avoid immunological rejection of transplanted organs. The risk of developing cancer is the most critical complication in organ transplant recipients undergoing immunosuppressive therapy. This study aims to explore the cytotoxic and genotoxic effects of TAC and MMF alone or combined orally administrated on spleen and bone marrow of Wistar rats. Our results showed that TAC (2.4; 24 and 60mg/kg) and MMF (5; 50 and 125mg/kg) induced a genotoxic effect on rat bone marrow. Moreover, the co-treatment with the TAC/MMF (2.4/5mg/kg b.w.; 2.4/50mg/kg b.w. and 60/50mg/kg b.w.) produce a genotoxicity as measured by micronuclei (MN) frequencies, chromosomal aberrations (CA) rates and DNA damage levels. Furthermore, the TAC and MMF-treated animals developed oxidative stress in spleen, indicated by a significant increase of malondialdehyde (MDA), protein oxidation and decrease of anti-oxidant enzymes levels such as catalase (CAT) and superoxide dismutase (SOD). This damage was associated with an increase of DNA fragmentation. Co-treatment with TAC/MMF synergistically induced markers of oxidative stress in rat splenic tissue. In conclusion, TAC/MMF associated induction in oxidative stress plays a role in the splenic and bone marrow toxicity and enhances the different endpoints of genotoxicity, suggesting its mutagenic action in vivo.

Protective effect of mycophenolate mofetil against nephrotoxicity and hepatotoxicity induced by tacrolimus in Wistar rats

Tacrolimus (TAC), a calcineurin inhibitor (CNI), is clinically used as an immunosuppressive agent in the transplant recipient; however, the use of TAC is greatly limited by its nephrotoxicity and hepatotoxicity. Mycophenolate mofetil (MMF), an inhibitor of the purine synthesis, has been used in combination with many immunosuppressive drugs such as TAC. The association TAC/MMF was used in organ transplantation to increase the efficiency and reduce acute rejection rates, but the effects of MMF on TAC-induced kidney and liver injuries are still not well investigated. The aims of this study are to explore whether MMF co-administration with TAC has a renoprotective and hepatoprotective effect against TAC-induced renal and hepatic injuries and to check the implication of oxidative stress in the MMF’s possible protective effect. Our results showed that MMF (at 50 mg kg−1 body weight (b.w.)) restored creatinine, in addition to increased AST and ALT levels by TAC (at 60 mg kg−1 b.w.). Furthermore, MMF decreased DNA damage induced by TAC in the kidney and liver of rats as assessed by comet assay. This renoprotective and hepatoprotective effect of MMF was associated with an antioxidant effect. In fact, MMF co-treatment with TAC decreased oxidative damage induced by TAC. It reduced malondialdehyde (MDA) and protein carbonyl (PC) levels as well as catalase and superoxide dismutase (SOD) activities. We conclude that the co-administration MMF with TAC protect liver and kidney against TAC toxicity via an antioxidant process (AU)

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Protective effect of mycophenolate mofetil against nephrotoxicity and hepatotoxicity induced by tacrolimus in Wistar rats.

Tacrolimus (TAC), a calcineurin inhibitor (CNI), is clinically used as an immunosuppressive agent in the transplant recipient; however, the use of TAC is greatly limited by its nephrotoxicity and hepatotoxicity. Mycophenolate mofetil (MMF), an inhibitor of the purine synthesis, has been used in combination with many immunosuppressive drugs such as TAC. The association TAC/MMF was used in organ transplantation to increase the efficiency and reduce acute rejection rates, but the effects of MMF on TAC-induced kidney and liver injuries are still not well investigated. The aims of this study are to explore whether MMF co-administration with TAC has a renoprotective and hepatoprotective effect against TAC-induced renal and hepatic injuries and to check the implication of oxidative stress in the MMF's possible protective effect. Our results showed that MMF (at 50 mg kg(-1) body weight (b.w.)) restored creatinine, in addition to increased AST and ALT levels by TAC (at 60 mg kg(-1) b.w.). Furthermore, MMF decreased DNA damage induced by TAC in the kidney and liver of rats as assessed by comet assay. This renoprotective and hepatoprotective effect of MMF was associated with an antioxidant effect. In fact, MMF co-treatment with TAC decreased oxidative damage induced by TAC. It reduced malondialdehyde (MDA) and protein carbonyl (PC) levels as well as catalase and superoxide dismutase (SOD) activities. We conclude that the co-administration MMF with TAC protect liver and kidney against TAC toxicity via an antioxidant process.

The evaluate and compare the effects of the Tacrolimus and Sirolimus on the intestinal system using an intestinal cell culture model.

Tacrolimus (TAC) and Sirolimus (SRL) are produced by Streptomyces sp and effective immunosuppressive drugs commonly used in organ transplantation. Therefore, strategies for minimizing the toxicity of immunosuppressant molecules are our interest. This study was conducted to evaluate the interactive effects and the possible underlying mechanism of TAC and SRL on HCT116 cells. It was found that TAC and SRL alone inhibited cell viability. Also, it induced reactive oxygen species (ROS) formation, loss of mitochondrial membrane potential (Δψm), and able to increase DNA fragmentation in a concentration-dependent manner. The use of combined SRL and TAC showed a reservation in all toxicity observed with the two immunosuppressive drugs separately. Our result demonstrated that the mechanisms of TAC and SRL at high concentration are closely connected with oxidative stress. Furthermore, SRL at low concentration plays a protective effect against TAC (IC50) which induced cytotoxicity and genotoxicity. However, using the combination of the SRL/TAC at high concentrations (IC30) appears as an antagonist response.