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Background. Generalized morphea is a rare fibrosing skin illness that progresses from erythematous, violet‐colored skin patches to sclerotic plaques. Another uncommon immune‐mediated connective tissue disease called eosinophilic fasciitis (EF) evolves to cause sclerosis and woody skin induration. The coexistence of the two is extremely rare and has a poorer prognosis. Our case report is one of the first to report burn injuries as a trigger factor for EF and generalized morphea overlap. Case Presentation. A 36‐year‐old man presented with acute onset of rapidly progressing skin thickening, tender edema, and skin contractures involving all extremities, shortly after enduring burn injuries from a gasoline explosion. Workup was remarkable for peripheral eosinophilia, hypergammaglobulinemia, and elevated C‐reactive protein. Skin biopsy demonstrated sclerodermoid changes and sclerotic thickening of subcutaneous fibrous septa associated with stromal mucin, dermal perivascular, diffuse lymphoplasmacytic infiltrate with eosinophils, decreased CD34 expression, and increased factor XIIIa. He was subsequently diagnosed with an overlap of generalized morphea and eosinophilic fasciitis. The patient had only limited improvement with steroids, methotrexate, mycophenolate mofetil, and intralesional triamcinolone acetonide injections. Conclusion. Generalized morphea with concomitant EF indicates some degree of therapeutic resistance and poor prognosis with a low quality of life. Burn injuries can be a trigger factor for this overlap syndrome. Prompt identification of at‐risk individuals and initiating aggressive management are necessary. [ABSTRACT FROM AUTHOR]

Idiopathic granulomatous mastitis (IGM) is a rare, benign inflammatory disorder of the breast that is often underrecognized. The exact etiology and pathophysiology are unknown, but milk stasis is felt to play a role. Classically, this condition is noninfectious, but many cases are noted to be associated with Corynebacterium species. Most patients affected are parous women with a mean age of 35, and many have breastfed within five years of diagnosis. Patients typically present with a painful mass and symptoms of inflammation, and these features can sometimes mimic breast cancer. Biopsy is needed to make a definitive diagnosis, and noncaseating granulomas are found on core biopsy. Many patients have a waxing and waning course over a period of six months to two years. Goal of treatment is to avoid surgery given poor wound healing, high risk of recurrence, and poor cosmetic outcomes. Medical treatment is preferred and includes observation, antibiotics, steroids, and immune modulators such as methotrexate. In more recent years, topical and intralesional steroids have become the treatment of choice, with similar outcomes to oral steroids. [ABSTRACT FROM AUTHOR]

Kimura's disease (KD) is a rare chronic inflammatory condition of unknown aetiology. It is a benign disease that might mimic a neoplastic process. It primarily affects the head and neck region, presenting as deep subcutaneous masses, and is often accompanied by triad regional lymphadenopathy, salivary gland involvement, and high serum immunoglobulin E (IgE) levels. Here, we report the second documented case of KD in Palestine diagnosed in a 28-year-old male patient who presented with lymphadenopathy and increased serum immunoglobulin E and G (IgE and IgG) associated with intermittent abdominal pain, generalised fatigue, hepatomegaly, cardiomyopathy, reactive airway disease, peripheral vasculopathy, peripheral neuropathy, and focal segmental glomerulosclerosis. The patient was managed with steroids and an immunosuppressant (Azathioprine) with a moderate response for two years. In 2021, treatment with Mycophenolate Mofetil was initiated, which was more effective than Azathioprine. [ABSTRACT FROM AUTHOR]

Objective. Enteric-coated mycophenolate sodium (EC-MPS) is widely used in renal transplant recipients. There is a lack of study on the pharmacokinetics of this drug in children. This study is aimed at developing a population pharmacokinetic model of mycophenolic acid in children who were treated with EC-MPS after renal transplantation and to recommend initial dosage. Methods. Pediatric patients who had undergone renal transplantation and received EC-MPS were included. Data on demographic characteristics, biochemical tests, blood routine examinations, mycophenolic acid plasma concentrations, dosing amount and frequency of EC-MPS, and coadministered medications were retrospective collected from June 2018 to August 2019. Nonlinear mixed effect modeling methods were adopted to develop a population pharmacokinetic model with the data above. Additional data from September 2019 to July 2020 were used to validate the model. Simulations under different dosage regimen were conducted to evaluate the percentage of target attainment (PTA, AUC0-12h 30–60 mg·h/L). Results. A total of 96 pediatric patients aged at 13.3 (range 4.3–18.0) years were included in the modeling group. Data from 32 patients aged at 13.0 (range 3.6–18.3) years were used to validate the model. A one-compartment model with a double extravascular absorption was developed. Body surface area (BSA) was added as a covariate. Simulations showed that for different dosing regimens, the highest percentage of target attainment is around 50%. The best dosing regimen is 180 mg every 48 hours for patients with BSA of 0.22–0.46 m2, 180 mg every 24 hours with BSA of 0.47–0.67 m2, 180 mg every 24 hours with BSA of 0.68–0.96 m2, 360 mg every 24 hours with BSA of 0.97–1.18 m2, 540 mg every 24 hours with BSA of 1.19–1.58 m2, and 360 mg every 12 hours with BSA of 1.59–2.03 m2. Conclusion. BSA could affect the area under curve of mycophenolic acid with the administration of EC-MPS. Considering the inflexibility of the dosage form, future development of smaller amount per tablet suitable for younger children with BSA < 1.19 m 2 is warranted. [ABSTRACT FROM AUTHOR]

Several blood biomarkers are now considered increasingly important for stratifying risk, monitoring disease progression, and evaluating the response to therapy in ischemic stroke. The purpose of the present study was to identify the key genes associated with ischemic stroke progression and elucidate the potential therapeutic small molecules. Microarray datasets related to stroke for GSE58294, GSE22255, and GSE16561 were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were filtered using the Limma package. DAVID was then searched to perform gene ontology (GO) and pathway enrichment analyses. Based on the DEGs, a protein-protein interaction (PPI) network was developed using Cytoscape, and MCODE was applied to conduct module analysis. Finally, to identify the potential drugs for ischemic stroke, the connectivity map (CMap) database was used. Sixty DEGs were identified after analyzing the three datasets. The GO data analysis revealed that the DEGs were significantly associated with biological processes, including positive regulation of programmed cell death, protein localization in organelles, and positive regulation of apoptosis. KEGG analysis showed that the DEGs were particularly enriched in the Fc epsilon RI signaling pathway, MAPK signaling pathway, and Huntington's disease. We selected five DEGs with high connectivity (CYBB, SYK, DUSP1, TNF, and SP1) that significantly predicted stroke progression. In addition, CMap prediction showed ten small molecules that could be used as adjuvants when treating ischemic stroke. The outcomes of the present study indicated that the five genes mentioned above can be considered potential targets for developing new medications that can modify the ischemic stroke process, and mycophenolic acid was the most promising small molecule to treat ischemic stroke. [ABSTRACT FROM AUTHOR]

Stiff skin syndrome (SSS) is a rare disorder characterized by skin induration and limited joint mobility in the absence of visceral, musculoskeletal, vascular, or immunologic abnormalities. Distinctive subsets of SSS could be distinguished by various manifestation and mechanism, which accounts for the high heterogeneity in SSS cases. Although rehabilitation training remains the mainstay of management, rising medications has drawn awareness in recent years, owing to the potential efficacy. Nevertheless, experience was limited, especially in widespread SSS. We report on a 5‐year‐old girl with widespread SSS, whose lesion stopped progressing after combination therapy by mycophenolic acid (MPA) and losartan (LST) in addition to rehabilitation exercise. Despite limited experience, a combined therapy of MPA and LST seems to be effective in retarding progression of widespread SSS. [ABSTRACT FROM AUTHOR]

Lichen planopilaris (LPP) is a chronic inflammatory disorder of hair without a proven effective and safe treatment. To objectively assess the clinical efficacy of mycophenolate mofetil (MMF) in patients suffering from LPP, a retrospective cohort study was conducted on 52 patients who treated with MMF (2 g/day) at least for 6 months. LPP activity index (LPPAI) before and after treatment was calculated and compared. Most of the patients were female and belonged to the age group of 50–60 years. All of the disease activity indices were significantly improved after 6 months of therapy (p < 0.001). The majority of patients had LPPAI 4–6 and 0–2, before and after treatment, respectively. After 6 months of treatment, half of patients showed a disease activity decrease (LPPAI reduced >25% compared to the baseline value). Systemic MMF is an effective and relatively safe treatment modality for patients with LPP and could lead to significant reduction in disease activity regarding both subjective and objective indices. [ABSTRACT FROM AUTHOR]

Background. Mizoribine (MZR) is widely used in Asia due to its high safety and low cost, and comparative studies of its safety and efficacy with the first-line drug mycophenolate mofetil (MMF) have been carried out. This paper aimed to compare the efficacy and safety of MZR and MMF in immunosuppressive therapy of renal transplantation by meta-analysis. Methods. We searched randomized controlled trials (RCTs) comparing MZR versus MMF for renal transplantation in PubMed, Excerpta Medica Database (EMBASE), Cochrane Library, Web of Science, WanFang Database, China National Knowledge Infrastructure (CNKI), and Chinese Biomedical Database (CBM). Articles were assessed for their risk of bias using the Cochrane Collaboration. Forest plots and funnel plots were also performed on the included articles. Results. A total of twelve studies with 1103 patients were selected in the analysis. No significant difference were observed between the MZR group and the MMF group for the rate of acute rejection (RR = 1.50, 95% CI 1.11 to 2.01, P = 0.008), patient survival (RR = 1.01, 95% CI 0.99 to 1.03, P = 0.56), graft survival (RR = 1.02, 95% CI 1.00 to 1.04, P = 0.12), leucopenia (RR = 0.69, 95% CI 0.44 to 1.10, P = 0.12), and liver damage (RR = 0.72, 95% CI 0.46 to 1.13, P = 0.15). The MZR group was associated with a lower risk of gastrointestinal disorder (RR = 0.28, 95% CI 0.13 to 0.62, P = 0.002) and cytomegalovirus infection (RR = 0.59, 95% CI 0.42 to 0.84, P = 0.003) but had a higher risk of hyperuricemia (RR 1.79, 95% CI 1.17 to 2.75, P = 0.007). No significant publication bias was observed among included studies. Discussion. MZR is similar to MMF in efficacy, and in terms of safety, MZR has a lower risk of gastrointestinal disorder and cytomegalovirus infection but a higher risk of hyperuricemia. [ABSTRACT FROM AUTHOR]

Objectives: Myasthenia gravis (MG) is an autoimmune disease characterized by muscle weakness and fatigue. Our objective was to investigate the incidence of MG using the National Health Insurance database of South Korea. Materials and methods: We conducted a retrospective cohort analysis of patients with the G70.0 code designated as MG and administered with MG medications for >3 months from 2007 to 2018 using nationwide data from South Korea. Results: A total of 8,376 patients with MG during the period of 2010–2018 were identified. There were 3,862 (46.1%) male and 4,517 (53.9%) female patients. The standardized incidence rate was 1.18/100,000 in 2010, and increased to 1.81/100,000 in 2018. The standardized prevalence was 7.50/100,000 in 2010, and changed to 11.15/100,000 in 2018. Pyridostigmine was used to treat 82.3 ± 1.2% of patients with MG during 2010–2018. Among MG patients, 85.7 ± 0.9% used steroids, 31.6 ± 4.8% used azathioprine, 12.9 ± 9.5% used tacrolimus, 7.2 ± 2.1% used cyclosporine, 6.2 ± 1.8% used mycophenolate mofetil, and 0.4 ± 0.1% used methotrexate. Thymectomy was performed in 1,130 MG patients, and the time from MG diagnosis to thymectomy decreased from 2010 to 2018. Conclusion: Based on the national registry data from 2010 to 2018, the incidence and prevalence rate in South Korea has increased. Whereas the use of IVIG has remained stable, thymectomy is performed earlier than before, and the distribution of immunosuppressant therapies has changed over the years with an increase in tacrolimus and mycophenolate mofetil. We expect that this study will serve as a basis for future South Korean MG epidemiological studies. [ABSTRACT FROM AUTHOR]

Prevention of neosporosis is advantageous for cattle health and productivity. Previously, several vaccine candidates were nominated for vaccination against Neospora caninum. This study was premised on in silico evaluation of N. caninum IMP-1 in order to determine its physicochemical features and immunogenic epitopes. We employed a wide array of network-based tools for the prediction of antigenicity, allergenicity, solubility, posttranslational modification (PTM) sites, physicochemical properties, transmembrane domains and signal peptide, secondary and tertiary structures, and intrinsically disordered regions. Also, prediction and screening of potential continuous B cell peptides and those epitopes having stringent affinity to couple with mouse major histocompatibility complex (MHC) and cytotoxic T lymphocyte (CTL) receptors were accomplished. The protein had 393 residues with a molecular weight of 42.71 kDa, representing aliphatic index of 85.83 (thermotolerant) and GRAVY score of -0.447 (hydrophilic). There were 47 PTM sites without a signal peptide in the sequence. Secondary structure comprised mostly of extended strand and helices, followed by coils. The Ramachandran plot of the refined model showed 90.1%, 9.9%, 0.0%, and 0.0% residues in the favored, additional allowed, generously allowed, and disallowed regions, correspondingly. Additionally, various potential B cell (linear and conformational), CTL, and MHC binding epitopes were predicted for N. caninum IMP-1. The findings of the present study could be further directed for next-generation vaccine design against neosporosis. [ABSTRACT FROM AUTHOR]

Objective. To analyze the diagnosis and treatment of patients with concomitant malignant tumors after organ transplantation by compiling data from organ transplantation patients. Methods. By searching CNKI and PubMed databases, we made a systematic analysis of the studies of postorgan transplantation complicating malignant tumors in the last decade. Results. There were 10 articles on malignant tumors after renal transplantation, 8 articles on liver transplantation, 2 articles on heart transplantation, and 1 article on lung transplantation. The incidence of malignant tumors complicating renal transplantation is 10.4% in Europe, with skin cancer and Kaposi's sarcoma being common; the incidence in the United States is 3.4%, with PTLD having the highest incidence; the incidence of malignant tumors is relatively lowest in Asia, with gastrointestinal malignancies being the main ones. The mean time to complication of malignancy after renal transplantation is 3.83 years. The incidence of concurrent malignancies after liver transplantation is 8.8% in Europe, where skin cancer and Kaposi's sarcoma are common; 5.6% in Asia, where gastrointestinal tract tumors are prevalent; and 4.5% in the United States, where gastrointestinal tract tumors, PTLD, and hematologic diseases are predominant. The mean time to complication of malignancy after liver transplantation is 4.79 years. The incidence of malignancy after heart transplantation is 6.8-10.7%. The incidence of malignancy after lung transplantation is about 10.1%. Minimization of immunosuppression or modification of immunosuppression regimens may be a key component of cancer prevention. mTOR inhibitors and phenolate (MMF) reduce the incidence of de novo malignancies in patients after solid organ transplantation. Surgical treatment improves survival in patients with early malignancies. The use of external beam radiation therapy in the treatment of hepatocellular carcinoma is limited due to the risk of radiation liver disease. Conclusions. The risk of concomitant malignancy needs to be guarded for 5 years of immunosuppressive therapy after organ transplantation surgery. Adjusting the immunosuppressive treatment regimen is an effective way to reduce concurrent malignancies. Systemic chemotherapy or radiotherapy requires vigilance against the toxic effects of drug metabolism kinetics on the transplanted organ. [ABSTRACT FROM AUTHOR]

Cutaneous lupus erythematosus (CLE) can be treated with multiple oral immunosuppressants but cost analyses of these treatments are lacking. We aimed to assess the relative cost difference between various oral medications for CLE using a cost‐minimization analysis. Annual direct costs for 10 oral medications used in CLE were calculated including cost of medications and patient monitoring, which include office visits, laboratory and radiological studies, and procedures. Medication costs were taken from the National Average Drug Acquisition Cost calculated by the Centers of Medicare and Medicaid Services or the Average Wholesale Price. Monitoring guidelines were obtained from expert consensus and FDA‐approved recommendations. Methotrexate had the lowest total direct cost ($899.31), followed by hydroxychloroquine ($1007.38), mycophenolate mofetil ($1162.12), azathioprine ($1193.71), chloroquine ($2525.01), dapsone ($2750.68), cyclosporine ($2976.32), thalidomide ($75,831.44), and lenalidomide ($316,104.03). For medications used for CLE patients, the medication cost contributes the most to differences between direct costs. Limitations include insufficient patient outcome data to ascertain medication efficacy, exclusion of cost of medication‐related adverse events and hospitalizations, and medication cost data not reflecting all payers. Clinicians can use this data to help discern which medication to prescribe CLE patients with financial constraints and reduce healthcare spending. [ABSTRACT FROM AUTHOR]

Structural optimization based on natural products is an important and effective way to discover new green pesticides. Here, two series of amide derivatives based on sinapic acid and mycophenolic acid were designed in combination with the fungicidal natural product piperlongumine and synthesized by preparing the carboxylic acid into acyl chloride and then reacting with the corresponding aromatic amines, respectively. The resulting structures were successively characterized by 1H NMR, 13 C NMR, and HRMS. The crystal structures of molecules I-4 and II-5 were analyzed for structure validation. The in vitro inhibitory activity indicated that most of the target products exhibited fungicidal activity equivalent to or even better than fluopyram against Physalospora piricola. The in vivo fungicidal activity demonstrated that the compounds I-5 and II-4 displayed almost the same preventative activity as carbendazim and fluopyram at 200 μg mL−1. The TEM observation revealed that the fungicidal activity of the target molecules against Physalospora piricola may be due to the influence on the mitochondria in the cell structure. These results will provide valuable theoretical guidance for developing the new green fungicides. [ABSTRACT FROM AUTHOR]

What is known and objective: Mycophenolate mofetil, an ester prodrug of mycophenolic acid (MPA), is widely used to prevent graft rejection after kidney transplantation. The pharmacokinetic (PK) of MPA has been extensively studied, which revealed a high degree of variability. An integrated population PK (PopPK) model of MPA and its main metabolite mycophenolic acid glucuronide (MPAG) was developed using the adult patients who underwent kidney transplant and were administered oral mycophenolate mofetil combined with tacrolimus. Methods: In total, 917 MPA and 740 MPAG concentrations in191 adult patients were analysed via nonlinear mixed‐effects modelling. The concentration‐time data were adequately described using a chain compartment model, including central and peripheral compartments for MPA and a central compartment for MPAG. Stepwise forward inclusion and backward elimination procedures were used to investigate the effects of genetic polymorphisms, including in UGT1A8, UGT1A9, UGT2B7, ABCB1, ABCC2, ABCG2, SLCO1B1, SLCO1B3, and HNF1α. Results and discussion: These genetic polymorphisms in metabolic enzymes and transporters have no obvious impact on the PK of MPA in adult patients who underwent kidney transplant and were co‐treated with tacrolimus. The post‐transplant time, serum albumin, and creatinine clearance were identified as significant covariates affecting the PK of MPA and MPAG, which should be considered in the clinical use of mycophenolate mofetil. What is new and conclusion: We established a PopPK model of MPA and MPAG in Chinese adult patients who underwent kidney transplant and were co‐treated with tacrolimus. Genetic polymorphisms in metabolic enzymes and transporters showed no obvious impact on MMF PK. A model‐informed dosing strategy was proposed by the established model, and MMF dose adjustment should be based on ALB levels and the post‐transplantation time. [ABSTRACT FROM AUTHOR]

Fewer than ten reported cases of cryptogenic organizing pneumonia (COP) have been managed with intravenous immunoglobulins (IVIg). We report a case of a 72-year-old man who presented with a worsening cough and diffuse opacities on chest radiograph. Following no improvement with antibiotics and negative complementary investigations for infectious, malignant, and autoimmune etiologies, COP was confirmed on lung biopsy. Due to continued clinical deterioration despite high-dose steroids and new severe steroid-induced hallucinations, the patient was placed on intravenous immunoglobulins (IVIg) and mycophenolate mofetil and made a satisfactory recovery. IVIg should be considered as an important steroid-sparing alternative in patients with COP. [ABSTRACT FROM AUTHOR]

Immune response after transplantation is the major cause of nucleus rejection and pearl oyster mortality during pearl production. Mycophenolate mofetil (MMF) is an immunosuppressant with low toxicity and strong immunosuppressive capacity and has been successfully used in reducing immune response in humans after organ transplantation. In this study, we evaluated the function of MMF in pearl production in pearl oyster Pinctada fucata martensii. Results showed that MMF treatment can significantly increase the retention rates without any significant effect on the survival rates and high‐quality pearl rates. Gene expression analysis by quantitative real‐time PCR (qRT‐PCR) showed that MMF can considerably down‐regulate the expression of nuclear factor κB (NF‐κB) at 6 h and 1–12 days and reduces the expression of the inhibitor of NF‐κB kinases (IκK) at 3–12 days after transplantation. Histological analysis indicated no difference in pearl sac development between the MMF treatment and control groups. These results suggested that MMF effectively regulates immune response induced by transplantation and improves the performance of pearl production in pearl oyster P. fucata martensii. [ABSTRACT FROM AUTHOR]

There are increasing reports of autoimmune and dermatologic sequelae of COVID‐19. We describe an otherwise healthy patient with recent history of serious COVID‐19 infection who developed post‐surgical pyoderma gangrenosum following bilateral reduction mammoplasty and was successfully treated with infliximab, mycophenolic acid, and corticosteroids. We present this case to highlight the lingering systemic proinflammatory effects of COVID‐19 infection that may increase the risk of rare autoimmune complications of surgery. As a complete understanding of the long‐term effects of COVID‐19 is poorly understood, patients with a history of COVID‐19 infection should be appropriately counseled to these possible risks when discussing surgery. [ABSTRACT FROM AUTHOR]

The term clinically amyopathic dermatomyositis (CADM) is used to represent a subgroup of patients with the typical cutaneous features of dermatomyositis (DM) in the absence of muscle involvement. Similar to classic DM, CADM can be associated with other connective tissue disorders and systemic manifestations such as interstitial lung disease and malignancy. Owing to the frequent discordance between muscle response and skin disease, the therapeutic approach to CADM represents a challenge. The current literature suggests that CADM treatment should follow a specific protocol, influenced by visceral involvement and the expression of certain myositis‐specific antibodies, and different from the recommendation in the presence of myositis. Here, we present five new cases of CADM. We describe the available therapeutic options for skin manifestations in this type of DM, and we propose a step‐by‐step therapeutic scheme, using the cutaneous dermatomyositis disease area and severity index to assess response. Our literature review establishes mycophenolate mofetil and intravenous immunoglobulin as the most frequently successful therapies in refractory skin disease. [ABSTRACT FROM AUTHOR]

What is known and objective: The removal rates of tacrolimus (TAC) and mycophenolic acid (MPA) by simultaneous plasma exchange (PE) and continuous hemodiafiltration (CHDF) are not clear. Case summary: We evaluated the removal rates of TAC and MPA by PE and CHDF started simultaneously 5 hours after administration in a lung transplant patient. TAC was not removed. MPA was transferred into the PE effluent, but the total amount in the effluent was only 1% of the dosage. What is new and conclusion: TAC and MPA were less likely to be removed by PE and CHDF initiated 5 hours after administration. [ABSTRACT FROM AUTHOR]

Palmo‐plantar lesions in discoid lupus erythematosus (DLE) can be considered a very distinct rarity, generally refractory to conventional treatments. We present a 47‐year‐old African female patient with a 6‐month clinical history of palm and soles erosions. Clinical examination revealed painful multiple, well defined, erosions with an erythematous and scaly central area and peripherical post‐inflammatory hyperchromic border bilaterally distributed on the palmo‐plantar surfaces. Pterygium inversum unguis involved all nails of both hands. Histological analysis and direct immunofluorescence study confirmed palmo‐plantar DLE. Therapy with mycophenolate mofetil (MMF) was initiated with a progressive clearing of palmo‐plantar lesions and a drastic reduction of pain. Therapy was well tolerated, neither side effects nor altered laboratory investigations were observed. Our case and literature review confirm that MMF may be an effective approach for the management of refractory palmo‐plantar DLE with a safer profile than Azathioprine regarding adverse effects and cutaneous malignancies risk. [ABSTRACT FROM AUTHOR]

Objectives. Mycophenolate mofetil (MMF) is the standard treatment for lupus nephritis. In Japan, it was approved for lupus nephritis in 2015. We investigated its real-world safety and effectiveness in Japanese patients with systemic lupus erythematosus (SLE). Methods. We analyzed the continuation rate, adverse events, and reasons for discontinuation of MMF in Japanese patients with SLE in a retrospective single-center study. We included 119 patients who received MMF from 31 July 2015 to 31 May 2019. To compare demographic and clinical characteristics between groups, the Mann–Whitney U -test was used for nonnormally distributed variables. Categorical variables were compared using Fisher's exact test. Kaplan–Meier curves were plotted for the discontinuation rate of MMF. Results. Patients consisted of 18 males and 101 females. Thirty-five patients discontinued MMF. The cumulative discontinuation rate was 42.4%. Twenty-nine patients discontinued MMF due to adverse events, and six patients discontinued MMF due to remission of SLE or desire for childbearing. At the time of the last observation, the lupus low disease activity state achievement rate was significantly lower in patients who experienced adverse events than those who did not (64% vs. 35%, P = 0.009). We examined the concentration of mycophenolate acid (trough level) in stored frozen serum in 11 patients. Two patients had irreversible complications due to viral meningitis; their trough mycophenolate acid concentrations were 8.3 and 6.3 μg/mL, respectively. Conclusions. Although MMF may be effective in Japanese patients with SLE, physicians should pay attention to infections in patients with high mycophenolate acid concentrations. [ABSTRACT FROM AUTHOR]

Herein we present a patient that underwent a liver transplant due to primary biliary cholangitis (PBC) and after 9 years developed multiple myeloma. Following the cessation of mycophenolate mofetil and 2 weeks after lenalidomide treatment was started, the patient experienced acute cellular rejection. The patient recovered after treatment with corticosteroids, resumption of mycophenolate mofetil, and cessation of lenalidomide. Lenalidomide-associated allograft rejection has been reported in other organs. However, this is the first case report of liver rejection induced by lenalidomide. [ABSTRACT FROM AUTHOR]

Mycophenolate mofetil (MMF) is associated with various gastrointestinal toxicities. However, limited literature studies exist reporting MMF-related gastrointestinal toxicity manifesting as esophageal strictures. We report a case of a 62-year-old male with kidney transplant on MMF, tacrolimus, and prednisone, presenting with progressive dysphagia and odynophagia. Esophagogastroduodenoscopy revealed severe esophageal stricturing with near food bolus impaction, requiring dilations, esophageal stent, and ultimately gastrostomy tube. Biopsies revealed nonspecific inflammation with no evidence of infectious/neoplastic process; thus, our multidisciplinary esophageal group determined that the process was secondary to MMF. This case demonstrates that, though rare, MMF can result in severe esophageal strictures causing significant morbidity. [ABSTRACT FROM AUTHOR]

Purpose. Although oral prednisolone is the first-line treatment for preventing recurrent optic neuritis (ON) after the completion of acute-phase treatment, especially anti-aquaporin 4 (AQP4) antibody-positive ON, and anti-myelin oligodendrocyte glycoprotein (MOG) antibody-positive ON, some patients experience relapses. Immunosuppressants could be effective in reducing the recurrence rate for neuromyelitis optica spectrum disorder and MOG antibody-related diseases, but there have been few studies addressing this issue focusing on the changes in ophthalmic parameters. The objective of the study was to analyze the impact of off-label uses of immunosuppressants to reduce recurrent ON. Design. Retrospective observational study, clinical case series. Methods. We reviewed the medical charts of 11 cases (22 eyes) who underwent immunosuppressive therapy in Kobe University Hospital and compared the annualized relapse rate (ARR) before and after immunosuppressive therapy. We also evaluated the dosage of prednisolone, complications of immunosuppressants, and other visual functional ophthalmologic parameters. Results. Eleven cases in total had AQP4 antibody (9 cases) and/or MOG antibody (3 cases). One case was double positive for these antibodies. Nine patients received azathioprine and two received mycophenolate mofetil as an initial immunosuppressive therapy. The median duration of immunosuppressant treatment was 2.8 years. The median ON ARR before immunosuppressive therapy was 0.33, and this decreased significantly to 0 after the therapy (p = 0.02). The dose of prednisolone was reduced from 17.8 ± 7.1 mg/day before to 5.8 ± 2.2 mg/day after immunosuppressive therapy (p < 0.01). Although two patients presented with mild elevation of liver enzymes and nausea, all patients were able to continue taking the immunosuppressants. Conclusions. Immunosuppressants can potentially decrease relapses and steroid dosage in patients with anti-AQP4 or MOG antibody-positive ON without severe adverse events and the exacerbation of visual acuities. [ABSTRACT FROM AUTHOR]

H syndrome is a complex multi‐organ disorder with autosomal recessive inheritance. The skin manifestations include early onset hyperpigmentation and hypertrichosis, followed by skin induration often diagnosed as scleromyxedema and morphea. There is no effective treatment. Our objective was to study the efficacy of mycophenolate mofetil in a patient with genetically confirmed H syndrome. We sought the genetic cause of H syndrome with whole‐exome sequencing (WES) of the proband. Genome‐wide homozygosity mapping (HM) provided additional evidence for causality of the variant suggested by WES. Here, we report a patient with characteristic clinical features of H syndrome, and the diagnosis was confirmed by identification of a homozygous SLC29A3 mutation (p.Gly437Arg). The patient was initially treated with prednisolone and cyclosporine, but after development of side‐effects she was placed on mycophenolate mofetil. After the treatment with mycophenolate mofetil was initiated, resolution of hyperpigmentation was noted, and no new lesions developed during an 18‐month follow‐up period. Thus, mycophenolate mofetil could be considered as a safe and partially effective treatment of H syndrome. [ABSTRACT FROM AUTHOR]

Background. Lupus nephritis (LN) can be complicated with requirement for kidney replacement therapy and death. Efficacy of induction therapies using mycophenolate mofetil (MMF) or intravenous cyclophosphamide (IVCYC) has been reported from studies, but there is limited data in Africans comparing both treatments in patients with proliferative LN. Methods. This was a retrospective study of patients with biopsy-proven proliferative LN diagnosed and treated with either MMF or IVCYC in a single centre in Cape Town, South Africa, over a 5-year period. The primary outcome was attaining complete remission after completion of induction therapy. Results. Of the 84 patients included, mean age was 29.6 ± 10.4 years and there was a female preponderance (88.1%). At baseline, there were significant differences in estimated glomerular filtration rate (eGFR) and presence of glomerular crescents between both groups (p ≤ 0.05). After completion of induction therapy, there was no significant difference in remission status (76.0% versus 87.5%; p = 0.33) or relapse status (8.1% versus 10.3%; p = 0.22) for the IVCYC and MMF groups, respectively. Mortality rate for the IVCYC group was 5.5 per 10,000 person-days of follow-up compared to 1.5 per 10,000 person-days of follow-up for the MMF group (p = 0.11), and there was no significant difference in infection-related adverse events between both groups. Estimated GFR at baseline was the only predictor of death (OR: 1.0 [0.9–1.0]; p = 0.001). Conclusion. This study shows similar outcomes following induction treatment with MMF or IVCYC in patients with biopsy-proven proliferative LN in South Africa. However, a prospective and randomized study is needed to adequately assess these outcomes. [ABSTRACT FROM AUTHOR]

Erdheim-Chester disease is a rare inflammatory disease that infiltrates skeletal and extra-skeletal tissue. Chronic kidney disease (CKD) in Erdheim-Chester disease is usually attributed to retroperitoneal lesions that lead to urologic obstruction and hydronephrosis. In this report, we describe a patient diagnosed with Erdheim-Chester disease who eventually developed end-stage kidney disease (ESKD). After complete remission of Erdheim-Chester disease by vemurafenib therapy and 2 years of hemodialysis, the patient underwent a deceased donor kidney transplantation with basiliximab induction and tacrolimus/mycophenolic acid maintenance. After conversion of mycophenolic acid to azathioprine due to cost, acute cellular rejection had occurred, and he was treated with steroid therapy. The patient remained in complete remission from Erdheim-Chester disease and dialysis-free 16 months after transplant. Kidney transplantation is another treatment option for those patients with Erdheim-Chester disease who suffer from renal failure in the setting of complete remission. [ABSTRACT FROM AUTHOR]

What is known and objective: Immunosuppression is the main goal in the treatment of autoimmune diseases, chronic inflammatory diseases, and solid organ and tissue transplantation. However, due to a lack of liquid‐form medications, it is challenging to achieve adequate immunosuppression when the patient is using enteral feeding tubes. It is necessary to transform solid oral medications into other forms for administration. Besides that, the occupational risk should be considered, and safety‐handling measures should be taken. This review aimed to investigate the available evidence regarding the use of immunosuppressive drugs through enteral feeding tubes, focusing on the administration technique, efficacy and treatment safety. Methods: We performed an integrative review using the databases PubMed, LILACS, SciELO, Cochrane and Google Scholar, including papers published between 1997 and 2017 in Portuguese, English and Spanish. We excluded editorials, theoretical reflections, abstracts presented at events, dissertations, theses, monographs and studies with extemporaneous formulations administered only by the oral route. In addition, we investigated the references of the included papers, as well as pharmaceutical guides, books and package inserts of selected drugs for additional evidence. Information and recommendations found were analysed and classified according to the GRADE system. Results and discussion: Fifty papers were identified, and 14 met the selection criteria. Among the assessed immunosuppressive drugs, we observed that tacrolimus, mycophenolic acid derivatives and azathioprine were the most studied, and they have more guided recommendations regarding their use through enteral feeding tubes. We noted the need for personal protective equipment for the conversion of the solid oral dosage forms, along with special caution during administration, due to occupational hazard. Other important factors identified were the position of the tube and interactions with the enteral nutrition, because they may compromise absorption, bioavailability and serum blood levels of immunosuppressive agents. However, the studies found have methodological limitations and poor quality, and this was taken into consideration during the classification of the evidence. What is new and conclusion: The lack of information about the administration of immunosuppressive drugs through enteral feeding tubes should not be a limiting factor, considering the need for treatment of patients in these circumstances. Risks and benefits must be carefully analysed, and factors regarding compounding and administration through the enteral tube must be considered before beginning treatment. Hence, more primary studies are necessary for better fundamental clinical management. [ABSTRACT FROM AUTHOR]

Statin-associated necrotizing autoimmune myositis (NAM) is an autoimmune condition characterized by severe acute-onset proximal muscle weakness, a very high creatinine kinase (CK) level, and prominent myofiber necrosis and minimal lymphocytic infiltration on muscle biopsy. Unlike self-limited statin myopathy, this condition usually requires aggressive immunomodulation therapy to assist recovery and prevent future disability. In this case report, we present a patient who developed progressive muscle weakness after taking atorvastatin for one year. At initial presentation, her CK level was 28,000 U/L. She was diagnosed with statin-associated NAM and started on high-dose intravenous solumedrol, mycophenolate, and intravenous immunoglobulin (IVIG) therapy. However, she subsequently developed acute bilateral vision loss and right side hemineglect; she was diagnosed with posterior reversible encephalopathy syndrome (PRES), thought to be a possible delayed adverse reaction to IVIG. IVIG was discontinued, and the patient was treated with supportive therapy. At six-month follow-up, she had significant improvement in muscle strength and vision. [ABSTRACT FROM AUTHOR]

Hypertension as a multifactorial pathology is one of the most important cardiovascular risk factors, affecting up to 30-40% of the general population. Complex immune responses are involved in the inflammatory mechanism of hypertension, with evidence pointing to increased inflammatory mediators even in prehypertensive patients. Increased vascular permeability, thrombogenesis, and fibrosis, effects that are associated with sustained hypertension, could be attributed to chronic inflammation. Chronic inflammation triggers endothelial dysfunction via increased production of ROS through proinflammatory cytokines. Increased serum level of proinflammatory cytokines such as IL-1β, IL-6, IL-8, IL-17, IL-23, TGFβ, and TNFα in hypertensive patients has been associated with either increased blood pressure values and/or end-organ damage. Moreover, some cytokines (i.e., IL-6) seem to determine a hypertensive response to angiotensin II, regardless of blood pressure values. Understanding hypertension as an inflammatory-based pathology gives way to new therapeutic targets. As such, conventional cardiovascular drugs (statins, calcium channels blockers, and ACEIs/ARBs) have shown additional anti-inflammatory effects that could be linked to their blood pressure lowering properties. Moreover, anti-inflammatory drugs (mycophenolate mofetil) have been shown to decrease blood pressure in hypertensive patients or prevent its development in normotensive individuals. Further research is needed to evaluate whether drugs targeting hypertensive-linked proinflammatory cytokines, such as monoclonal antibodies, could become a new therapeutic option in treating arterial hypertension. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease that may affect any organ of the body. Lupus nephritis (LN) is a frequent and serious complication of SLE. We report a case of an 80-year-old woman who was initially diagnosed with late-onset SLE and eventually developed LN in the setting of normal complements, double-stranded DNA, C-reactive protein, erythrocyte sedimentation rate, and urine sediment. She developed abnormal renal function (creatinine of 1.7 mg/dl) and mild proteinuria (1-2+) without hematuria. Renal biopsy showed class IV lupus glomerulonephritis, active and chronic. The patient was started on mycophenolate mofetil which led to improvement of proteinuria and stabilization of creatinine. The suspicion for LN in a patient with late-onset SLE should remain high when there is development of suspicious renal or urinary abnormalities even if laboratory values do not suggest high disease activity and urinary sediment is normal. To our knowledge, this is one of the oldest patients with biopsy-proven LN and late-onset SLE. [ABSTRACT FROM AUTHOR]

Posterior reversible encephalopathy syndrome (PRES) is a rare and poorly understood neurologic condition that has been described in some patients with systemic lupus erythematosus (SLE). Intracerebral hemorrhage is a unique and atypical presentation of PRES and has been described only in a small number of patients with SLE. We present the case of a 33-year-old female, diagnosed with SLE and active nephritis, who was admitted for seizures. She had acute-onset headache, confusion, and bilateral vision loss associated with severe hypertension. CT scan revealed right occipital and parietal lobe hemorrhage. MRI showed vasogenic edema and hyperintense foci in bilateral cortical and subcortical regions of the occipital and posterior parietal lobes which are consistent with posterior reversible encephalopathy syndrome (PRES). Strict blood pressure control and medical ICP-lowering treatment were immediately instituted, while maintaining her on anticonvulsants, high-dose steroids, and mycophenolate mofetil. The patient was discharged with improvement in vision and resolution of headache. On follow-up, she had gained her premorbid visual acuity and reported no recurrence of headache or seizures. Despite its name, reversibility remains to be conditional in PRES. A high index of suspicion is important, especially among those who present with seizure, headache, and visual loss. Early diagnosis and timely initiation of therapy is recommended, as clinical symptoms are potentially reversible and delayed therapy may result in life-threatening complications, such as coma or death. [ABSTRACT FROM AUTHOR]

Background. Graves’ ophthalmopathy (GO) is a complicated autoimmune disease. Various therapies have been used to manage GO; however the optimum therapy is not clear. Glucocorticoids (GCs) therapy is the mainstay of treatment especially for active moderate to severe patients, which needs evidence-based support. Method. We searched all the randomized controlled trials (RCTs) involving corticosteroid treatment for patients diagnosed with GO from EMBASE, Medline, and the Cochrane library and then conducted a system review and meta-analysis. The electronic search covered the period from April 1966 to March 2018. Result. Twenty-nine trials were included. GCs were proved to be beneficial for GO patients [response rate, risk ratio (RR) = 1.72, 95% confidence interval (CI): 1.28~2.31, P=0.0003], and intravenous corticosteroids worked significantly better than oral corticosteroids as ever reported. When compared with the single treatment of GCs, the combination of radiotherapy and GCs showed similar effects on response rate (RR=1.25, 95%CI: 0.91~1.73). A study proved the advantage of mycophenolate mofetil over GCs in three outcomes (response rate, RR=0.74, 95%CI: 0.63~0.88). Additional treatments such as technetium-99 methylene diphosphate (99Tc-MDP) or cyclosporine enhanced the effect of GCs on proptosis reduction, respectively (P<0.00001 and P=0.02). Conclusion. Our meta-analysis confirmed the effects of GCs in the management of GO and intravenous GCs are proved to be better than oral GCs as ever reported. Combination of radiotherapy and GCs did not enhance the effects of GCs. However, if proptosis is the main issue, combination of 99Tc-MDP or cyclosporine with GCs may be taken into consideration. The reported advantages of mycophenolate mofetil over GCs are noteworthy and need more RCTs to confirm. [ABSTRACT FROM AUTHOR]

Macrophage activation syndrome (MAS) is a rare manifestation of systemic lupus erythematosus (SLE) with potentially life-threatening consequences. To the best of our knowledge, this is the first case reported in literature for a constellation of MAS, glomerulonephritis, pericarditis, and retinal vasculitis as initial presentation of SLE. Despite extensive multisystem involvement of his disease, the patient responded well to initial steroid treatment, with mycophenolate mofetil successfully added as a steroid-sparing agent. Our case highlights the importance of multispecialty collaboration in the diagnosis and management of SLE with multisystem involvement. [ABSTRACT FROM AUTHOR]

Objective. To assess practice pattern similarities and differences amongst pediatric rheumatologists and nephrologists in the management of pediatric Granulomatosis with Polyangiitis (GPA). Methods. A voluntary survey was distributed to the Midwest Pediatric Nephrology Consortium Group (MWPNC) and an international pediatric rheumatology email listserv in 2016-2017. Data were collected on general practice characteristics and preferences for induction management under three clinical scenarios (A-C): newly diagnosed GPA with glomerulonephritis, GPA with rapidly progressive glomerulonephritis, and GPA with pulmonary hemorrhage. In addition, individual preferences for GPA maintenance medications, disease monitoring, and management of GPA with end-stage renal disease were ascertained. Results. There was a 68% response rate from the MWPNC membership and equal numbers of rheumatology respondents. Survey results revealed Rituximab plus Cyclophosphamide is a more common induction choice for rheumatologists than nephrologists in induction Scenarios A and B, whereas Cyclophosphamide is more commonly chosen by nephrologists in Scenario A. Plasmapheresis rates increased for Scenarios A, B, and C for both specialties, but were overall low. There was no clear consensus on the duration of maintenance therapy nor diagnostic work-up. Rheumatologists more frequently chose Rituximab for maintenance and induction compared to nephrologists. There was also a higher than expected proportion of Mycophenolate Mofetil use for both specialties. Conclusion. This survey has revealed important differences in the way that rheumatologists and nephrologists manage this disease. It highlights the need for well-designed clinical trials in pediatric GPA patients and reveals that both specialties must be represented during consensus-building and clinical trial design efforts. [ABSTRACT FROM AUTHOR]

The combination of immunosuppressants and mesenchymal stem cells (MSCs) is a promising therapeutic strategy for systemic lupus erythematosus, since this approach reduces doses of immunosuppressants while maintaining the same therapeutic outcome. However, it is unavoidable for MSCs to be exposed to immunosuppressants. Here, we examined the combination effect of prednisone (PD) or mycophenolate mofetil (MMF) and MSCs. We showed that PD or MMF in combination with MSCs showed better therapeutic effect than single therapy in lupus-prone MRL.Faslpr mice, as assessed by using the following readouts: prolongation of survival, decrease in anti-dsDNA and total IgG levels in serum, decrease in cytokine gene expression in spleen cells, and decrease in inflammatory cell infiltration into the kidney. In vitro, immunosuppressants and MSCs inhibited T cell proliferation in a synergistic manner. However, immunosuppressants did not affect MSC viability and functions such as TGF-β1 and PGE2 production, migration, and immunosuppressive capacity. In summary, our study demonstrates that a combination of immunosuppressants and MSCs is a good strategy to reduce the side effects of PD and MMF without the loss of therapeutic outcome. [ABSTRACT FROM AUTHOR]

Background. Despite earlier studies describing the feasibility of steroid weaning in heart transplant patients, the majority of patients are maintained on steroid therapy for life. We examined a strategy based on a single morning serum cortisol measurement. Methods. We assigned stable posttransplant patients, who were maintained on tacrolimus, mycophenolate mofetil, and corticosteroids, into one of two groups based on a screening morning cortisol level. Patients with a cortisol < 8 micrograms/deciliter were assigned to a “maintenance” group and the others were assigned to the weaning group and steroids were tapered off over 4–6 weeks. Patients were monitored on subsequent office visits for adrenal insufficiency and allograft rejection. Results. Thirty-one patients were enrolled (6 patients in the maintenance group and 25 in the steroid-weaning group). Mean follow-up was 10.2±4 years for the weaning group and 9.0±4.9 years in the maintenance group (p=0.6). No cases of rejection were noted, nor did any patient resume steroid treatment following discontinuation. Conclusion. Steroids can be safely discontinued in stable heart transplant patients with an AM serum cortisol ≥ 8 micrograms/deciliter with appropriate outpatient follow-up. In this study, no patient suffered late rejection or clinically noted adrenal insufficiency. [ABSTRACT FROM AUTHOR]

Diarrhea following organ transplantation is usually associated with infection and immunosuppression therapy. We describe two patients with diarrhea following orthotopic heart transplantation due to tertiary adrenal insufficiency. [ABSTRACT FROM AUTHOR]

Lupus nephritis is one of the most severe Systemic Lupus Erythematosus features, defining treatment modality and prognosis. Our retrospective study, including 178 patients treated for lupus nephritis during 23 years with mostly cyclophosphamide-based initial regimens followed by azathioprine or mycophenolic acid, demonstrates 84.8% of renal response with 19.2% of flares, 15-year patient survival 78.7% and kidney survival 76.3%, and low damage accrual. Both patient and kidney survival significantly differ for subgroups that achieved complete or partial renal response and nonresponders: patient 15-year survival 95% versus 65% versus 35%; kidney 15-year survival 100% versus 58% versus 0%, respectively. 51% (24 out of 47) of patients evaluated at the end of the study period sustained complete renal response; however, only 9 of them had 0 disease activity according to SELENA SLEDAI scale, while 13 patients had scores 2–4 due to the serological abnormalities only. We conclude that (1) initial treatment with cyclophosphamide followed by azathioprine is effective and can be used in agreement with International Guidelines until the evidence for biological treatments benefits becomes available; (2) complete and even partial renal response have positive prognostic value, and failure to achieve renal response negatively influences kidney and patient survival; (3) the validity of complete renal response in SLE is questioned by the absence of conventional definition of SLE remission. [ABSTRACT FROM AUTHOR]

Objective. Systemic lupus erythematosus (SLE) is an autoimmune disease identified by a plethora of production of autoantibodies. Autoreactive T cells may play an important role in the process. Attenuated T cell vaccination (TCV) has proven to benefit some autoimmune diseases by deleting or suppressing pathogenic T cells. However, clinical evidence for TCV in SLE is still limited. Therefore, this self-controlled study concentrates on the clinical effects of TCV on SLE patients. Methods. 16 patients were enrolled in the study; they accepted TCV regularly. SLEDAI, clinical symptoms, blood parameters including complements 3 and 4 levels, ANA, and anti-ds-DNA antibodies were tested. In addition, the side effects and drug usage were observed during the patients' treatment and follow-up. Results. Remissions in clinical symptoms such as facial rash, vasculitis, and proteinuria were noted in most patients. There are also evident reductions in SLEDAI, anti-ds-DNA antibodies, and GC dose and increases in C3 and C4 levels, with no pathogenic side effects during treatment and follow-up. Conclusions. T cell vaccination is helpful in alleviating and regulating systemic lupus erythematosus manifestation. [ABSTRACT FROM AUTHOR]

We herein describe the first case of thrombotic microangiopathy (TMA) which was related to Shiga toxin producing-Escherichia Coli Hemolytic and Uremic Syndrome (STEC-HUS) after lung transplantation. His maintenance immunosuppression relied on tacrolimus plus mycophenolic acid. TMA was treated with plasma exchanges (PE) (fresh frozen plasma substitution). After five days of PE, platelets count and lactate dehydrogenase level normalized, whereas hemoglobin continued to gradually decrease and no improvement in kidney function was observed. After seven PE sessions, all TMA biological signs resolved. However, kidney function did not improve, and the patient still required chronic dialysis. [ABSTRACT FROM AUTHOR]

Autoimmune haemolytic anaemia is not a well-recognised complication of sarcoidosis. We describe the case of a 30-year-old female who presented with acute warm haemolytic anaemia and widespread lymphadenopathy. Sarcoidosis was diagnosed on lymph node biopsy and further investigation. The haemolytic anaemia responded only to a high dose of steroids. Evidence regarding treatment of steroid refractory autoimmune haemolysis secondary to sarcoidosis is lacking. Based on the emergent evidence that both disorders share common immunopathogenic mechanisms involving Th1 and Th17 lymphocytes, our patient was given rituximab and mycophenolate mofetil to successfully suppress the haemolysis and sarcoid activity. [ABSTRACT FROM AUTHOR]

Objective The transplant vasculopathy as a sign of chronic graft rejection affects both the epicardial and the intramyocardial arteries of the graft. This is at least partially mediated by NO synthases. The aim of this study was to assess possible protective effects of cyclosporine A (CsA), tacrolimus ( FK506), and mycophenolate mofetil ( MMF) on the expression of NO synthases in an experimental transplant rat model. Aims Heart transplantation was performed in 322 rats. These were randomly assigned to four equal groups (control, CsA, FK506, MMF). Recipients were monitored up to 60 days after transplantation, while transplanted hearts were recovered at certain time points for analysis. Expression and staining intensity for endothelial nitric oxide synthases (e-nos) and inducible nitric oxide synthases (i-nos) were analyzed in epicardial and intramyocardial vessels in each group. Results All employed drugs led to a significant reduction of expression or staining intensity of i-nos and e-nos. MMF was most effective in reduction in expression of both NO synthases. Conclusions These results imply that all described drugs prevent endothelial impairment induced by toxicity of NO and thereby prevent transplant vasculopathy. MMF seems to be the most effective drug. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to investigate the efficacy and safety of a transient intensified enteric-coated mycophenolate sodium (EC-MPS) dosing regimen with low exposure of calcineurin inhibitors (CNIs) in Chinese de novo kidney transplantation.Methods: In a 6-month prospective study, a total of 97 recipients were enrolled and assigned to either an intensified EC-MPS dosing (IS) regimen or a standard EC-MPS dosing (SD) regimen. The area under the curve (AUC) of MPA was assessed at week 1 post transplant. The incidences of acute rejection, patient and graft survival, renal allograft function and adverse events were analysed.Results: The IS regimen displayed a trend of acute rejection risk reduction (IS 2.7% vs. SD 13.3%, p = 0.061) and allograft function improvement (IS 62.8 ± 14.0 ml/min per 1.73 m(2) vs. SD 56.6 ± 18.3 ml/min per 1.73 m(2) , p = 0.084) after 6-month follow-up. MPA-AUC0-12 h was substantially higher in the intensified EC-MPS group than the standard EC-MPS group, though without a significant difference (71.4 ± 41.7 vs. 53.0 ± 27.0 mg·h/l, p = 0.107). The IS regimen did not increase the incidence of adverse effects (IS 54.1% vs. 45.0%, p = 0.39), including diarrhoea or leucopenia.Conclusions: The intensified EC-MPS dosing regimen maintaining low-dose CNIs in this study may be beneficial for Chinese adult de novo kidney transplant recipients in terms of acute rejection and allograft function and is safe within 6 months post transplant. [ABSTRACT FROM AUTHOR]