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Magoba, Moses, and Mimonitu Opuwari. "Petrophysical interpretation and fluid substitution modelling of the upper shallow marine sandstone reservoirs in the Bredasdorp Basin, offshore South Africa." Journal of Petroleum Exploration and Production Technology 10, no. 2 (November 7, 2019): 783–803. http://dx.doi.org/10.1007/s13202-019-00796-1.
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Abstract The fluid substitution method is used for predicting elastic properties of reservoir rocks and their dependence on pore fluid and porosity. This method makes it possible to predict changes in elastic response of a rock saturation with different fluids. This study focused on the Upper Shallow Marine sandstone reservoirs of five selected wells (MM1, MM2, MM3, MM4, and MM5) in the Bredasdorp Basin, offshore South Africa. The integration of petrophysics and rock physics (Gassmann fluid substitution) was applied to the upper shallow marine sandstone reservoirs for reservoir characterisation. The objective of the study was to calculate the volume of clay, porosity, water saturation, permeability, and hydrocarbon saturation, and the application of the Gassmann fluid substitution modelling to determine the effect of different pore fluids (brine, oil, and gas) on acoustic properties (compressional velocity, shear velocity, and density) using rock frame properties. The results showed average effective porosity ranging from 8.7% to 16.6%, indicating a fair to good reservoir quality. The average volume of clay, water saturation, and permeability values ranged from 8.6% to 22.3%, 18.9% to 41.6%, and 0.096–151.8 mD, respectively. The distribution of the petrophysical properties across the field was clearly defined with MM2 and MM3 revealing good porosity and MM1, MM4, and MM5 revealing fair porosity. Well MM4 revealed poor permeability, while MM3 revealed good permeability. The fluid substitution affected rock property significantly. The primary velocity, Vp, slightly decreased when brine was substituted with gas in wells MM1, MM2, MM3, and MM4. The shear velocity, Vs, remained unaffected in all the wells. This study demonstrated how integration of petrophysics and fluid substitution can help to understand the behaviour of rock properties in response to fluid saturation changes in the Bredasdorp Basin. The integration of these two disciplines increases the obtained results’ quality and reliability.
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Militano, Olga, Kate Roache, Leslie M. Shaw, Michael Figurski, Prakash Satwani, Janet Ayello, Karen Wolownik, et al. "Pharmacokinetics (PK) of Mycophenolate Mofetil (MMF) in Pediatric Allogeneic Stem Cell Transplant (AlloSCT) Recipients Are Associated with Significantly Higher Clearance." Blood 106, no. 11 (November 16, 2005): 1823. http://dx.doi.org/10.1182/blood.v106.11.1823.1823.
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Abstract We have previously reported altered PK requiring significantly higher doses of MMF in pediatric AlloSCT recipients (Osunkwo et al, BBMT 2004). The objective of this study is to further evaluate effects of age and type of conditioning regimen (ablative vs reduced intensity on the PK of MMF in pediatric AlloSCT recipients. From Jan ’04 through April ’05 we have enrolled 21 pediatric AlloSCT recipients in an IRB approved protocol. Mean age 6.2 yrs (0.33–15); weight 28.6 kg (5.7–129.3); M:F = 11:10; NBL PR (n=3), SCD (n=2), AML (CR1 [n=2], CR2 [n=1], CR3 [n=1], relapsed [n=1], induction failure [n=1]), SAA (n=2), CML CP (n=1), ALL (CR1 [n=1], CR2 [n=1], CR3 [n=1]), WAS (n=1), HD CR2 (n=1), ALCL refractory (n=1), SCID (n=1); donor sources included MFD (6/6 PBSC [n=5], 6/6 BM [n=1], 5/6 PBSC [n=2]), 6/6 related CB (n=1), UCB (6/6 [n=2], 5/6 [n=2], 4/6 [n=7]), and 8/10 MUD PBSC (n=1). Cohort 1 (< 6 yrs) (n=10); 2 (6–12 yrs of age) (n=6); 3 (12–16 yrs) (n=5). GVHD prophylaxis included tacrolimus and MMF (+ methotrexate for MUD). Tacrolimus was initiated on Day −1 or 1st day of conditioning (protocol dependent) at 0.03 mg/kg/d CI or 0.12 mg/kg/d PO Q8–12H to maintain concentrations 5–20 ng/mL. MMF was initiated on Day +1 at 900 mg/m2/dose IV Q6H and then converted to PO (same dose) on Day +14 or later. MMF PK was performed on Day +1, +7, and +14 (while on IV MMF) at hour 0, 0.5, 1, 2, 3, 4, and 6 post-dose. MPA plasma concentrations were determined by reverse-phase HPLC. MMF dose was adjusted to maintain MPA trough 1–3.5 mcg/mL. The mean CD34+ cell dose/kg = 23 x 105, nucleated cell dose/kg = 45 x 107. Time to neutrophil engraftment (ANC ≥ 500/mm3 x 2 d) was 22 d and platelet engraftment (untransfused count ≥ 20K x 7 d) was 28 d. The mean f/u was 241 d. Mean MPA PK on Day +14 demonstrated Cmax=12.4 mg/L, total MPA trough =0.9 mg/L, AUC0–12=32.7 mcg•hr/mL, Css=2.7 mg/L, T1/2=1.5 h, Vss=1.8 L/kg, and CL=1.4 L/kg/h at a mean MMF dose of 1080 mg/m2 IV Q6H. The breakdown of age cohorts is shown in Table 1. Gastrointestinal adverse events attributable to MMF occurred in 50% of patients (grade 2–3 nausea (n=9), grade 2–3 vomiting (n=4), abdominal pain (n=2), pneumatosis intestinalis (n=1), colitis (n=1)). Kaplan-Meier probability of grade II–IV aGVHD (18 evaluable pts) was 71.1% (CI: 46.9–95.4) and cGVHD (15 evaluable pts) was 37.7% (CI: 8.2–67.1). In comparison to MMF PK in adult AlloSCT pts receiving cyclosporine/MMF (Nash et al, BBMT 2005), pediatric pts appear to have significantly higher MMF clearance rates (1.4 vs 0.54 L/kg/h). MMF doses > 3-fold higher than those used in pediatric SOT recipients were required to achieve AUC0–12=30–60 mcg•h/mL. Short half-life (1.5 hrs) and rapid clearance of MMF in pediatric AlloSCT recipients in part appear related to a lack of enterohepatic recycling and enhanced UDP-glucuronosyltransferase activity. Table 1. Age-Based MMF PK in Pediatric AlloSCT Recipients on Day +14 Age Group < 6 y.o. (n=6) 6–12 y.o. (n=5) 12–16 y.o. (n=2) Cmax(mg/L) 12.2 11.8 14.4 Total MPA trough (mg/L) 1.0 0.4 1.4 Free MPA trough (ng/mL) 18.7 14.8 17.9 Mean AUC0–12 (mcg•h/mL) 34 29.5 39.9 Mean total Css (mg/L) 2.8 2.5 3.3 T1/2 (h) 1.8 1.1 1.5 Vss(L/kg) 2.1 1.8 0.5 CL (L/kg/h) 1.6 1.4 0.6
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Aslam-Pervez, Nawaf, John F. Caccamese, and Gary Warburton. "A randomized prospective comparison of maxillomandibular fixation (MMF) techniques: “SMARTLock” hybrid MMF versus MMF screws." Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology 130, no. 6 (December 2020): 640–44. http://dx.doi.org/10.1016/j.oooo.2020.07.015.
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Li, Shengde, Haitao Ren, Yan Xu, Tao Xu, Yao Zhang, Hexiang Yin, Weihua Zhang, et al. "Long-term efficacy of mycophenolate mofetil in myelin oligodendrocyte glycoprotein antibody-associated disorders." Neurology - Neuroimmunology Neuroinflammation 7, no. 3 (March 13, 2020): e705. http://dx.doi.org/10.1212/nxi.0000000000000705.
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ObjectiveTo investigate whether the use of mycophenolate mofetil (MMF) could reduce the relapse risk in patients with myelin oligodendrocyte glycoprotein (MOG)-immunoglobulin G (IgG)-associated disorders (MOGADs).MethodsThis prospective observational cohort study included patients with MOGAD at Peking Union Medical College Hospital between January 1, 2017, and April 30, 2019. The patients were divided into 2 groups: those with (MMF+) or without (MMF−) MMF therapy. The primary outcome was relapse at follow-up. We used Cox proportional hazards models to calculate hazard ratios (HRs) for relapse.ResultsSeventy-nine patients were included in our MOG cohort. Fifty (63.3%) were adults at index date, and 47 (59.5%) were women. Fifty-four (68.4%) were in the MMF+ group, and 25 (31.6%) were in the MMF− group. Clinical and demographic factors, MOG-IgG titer, and follow-up time (median, 472.5 days for MMF+, 261.0 days for MMF−) were comparable between the groups. Relapse rates were 7.4% (4/54) in the MMF+ group and 44.0% (11/25) in the MMF− group. Of all potential confounders, only the use of MMF was associated with reduced risk of relapse. The HR for relapse among patients in the MMF+ group was 0.14 (95% CI, 0.05–0.45) and was 0.08 (95% CI, 0.02–0.28) in a model adjusted for age, sex, disease course, and MOG-IgG titer. MMF therapy also remained associated with a reduced relapse risk in sensitivity analyses. Only one patient (1.9%) discontinued MMF therapy because of adverse effect.ConclusionsThese findings provide a clinical evidence that MMF immunosuppression therapy may prevent relapse in patients with MOGAD.Classification of evidenceThis study provides class IV evidence that for patients with MOGAD, MMF reduces relapse risk.
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Franco, Martha, Flavio Martínez, Bernardo Rodríguez-Iturbe, Richard J. Johnson, José Santamaría, Angélica Montoya, Tomas Nepomuceno, Rocío Bautista, Edilia Tapia, and Jaime Herrera-Acosta. "Angiotensin II, interstitial inflammation, and the pathogenesis of salt-sensitive hypertension." American Journal of Physiology-Renal Physiology 291, no. 6 (December 2006): F1281—F1287. http://dx.doi.org/10.1152/ajprenal.00221.2006.
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Transient administration of ANG II causes persistent salt-sensitive hypertension associated with arteriolopathy, interstitial inflammation, and cortical vasoconstriction; blocking the vascular and inflammatory changes with mycophenolate mofetil (MMF) prevents vasoconstriction. While infiltrating leukocytes during the salt-sensitive hypertension phase express ANG II, the functional role of ANG II during this phase is not known. We examined the acute effect of candesartan on renal hemodynamics during the established salt-sensitive hypertensive phase and related these findings to direct measurement of intrarenal ANG II and inflammatory cells in rats previously exposed to ANG II with or without MMF treatment. Sham controls were also examined. The administration of ANG II, followed by exposure to high-salt diet, resulted in hypertension, cortical vasoconstriction, an increase in interstitial inflammatory cells (44.8 ± 1.3 lymphocytes/mm2, and 30.8 ± 1.2 macrophages/mm2 ANG II vs. 19.6 ± 2 lymphocytes/mm2, and 22 ± 0.7 macrophages/mm2 Sham), and increase in renal ANG II levels (1,358 ± 74.6 pg/ml ANG II vs. 194 ± 9.28 pg/ml Sham). Treatment with MMF during the administration of exogenous ANG II resulted in reduction in renal interstitial inflammation (19.7 ± 0.9 lymphocytes/mm2 and 15.9 ± 0.8 machophages/mm2), ANG II levels (436.9 ± 52.29 pg/ml), cortical vasoconstriction, and stable blood pressure levels during the subsequent challenge with a high-salt diet. Acute administration of candesartan similarly reduced renal vasoconstriction and blood pressure. We conclude that the cortical vasoconstriction occurring with salt-sensitive hypertension following exposure to ANG II is mediated by intrarenal ANG II, related, at least in part, to the interstitial inflammation.
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Wang, Qi, and Yu Liu. "Optical fiber curvature sensor based on MMF-SCF-MMF structure." Optical Fiber Technology 43 (July 2018): 1–5. http://dx.doi.org/10.1016/j.yofte.2018.03.010.
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Peng, Yaping, Tie Liu, Sheng-Li Qin, Tapas Baug, Hong-Li Liu, Ke Wang, Guido Garay, et al. "ATOMS: ALMA Three-millimeter Observations of Massive Star-forming regions – X. Chemical differentiation among the massive cores in G9.62+0.19." Monthly Notices of the Royal Astronomical Society 512, no. 3 (March 9, 2022): 4419–40. http://dx.doi.org/10.1093/mnras/stac624.
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ABSTRACT Investigating the physical and chemical structure of massive star-forming regions is critical for understanding the formation and early evolution of massive stars. We performed a detailed line survey toward six dense cores, named MM1, MM4, MM6, MM7, MM8, and MM11, in the G9.62+0.19 star-forming region resolved in Atacama Large Millimeter/submillimeter Array (ALMA) band 3 observations. Toward these cores, about 172 transitions have been identified and attributed to 16 species, including organic oxygen-, nitrogen-, and sulphur-bearing molecules and their isotopologues. Four dense cores, MM7, MM8, MM4, and MM11, are line-rich sources. Modelling of these spectral lines reveals that the rotational temperature lies in the range 72–115, 100–163, 102–204, and 84–123 K for MM7, MM8, MM4, and MM11, respectively. The molecular column densities are 1.6 × 1015–9.2 × 1017 cm−2 toward the four cores. The cores MM8 and MM4 show a chemical difference between oxygen- and nitrogen-bearing species, i.e. MM4 is rich in oxygen-bearing molecules, while nitrogen-bearing molecules, especially vibrationally excited HC3N lines, are mainly observed in MM8. The distinct initial temperatures at the accretion phase may lead to this N/O differentiation. Through analysing column densities and spatial distributions of O-bearing complex organic molecules (COMs), we found that C2H5OH and CH3OCH3 might have a common precursor, CH3OH. CH3OCHO and CH3OCH3 are likely chemically linked. In addition, the observed variation in HC3N and HC5N emission may indicate their different formation mechanisms in hot and cold regions.
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DeBiasio, Justin C., Mary E. Russell, Robert J. Butler, James A. Nunley, and Robin M. Queen. "Changes in Plantar Loading Based on Shoe Type and Sex During a Jump-Landing Task." Journal of Athletic Training 48, no. 5 (October 1, 2013): 601–9. http://dx.doi.org/10.4085/1062-6050-48.3.08.
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Context: Metatarsal stress fractures are common in cleated-sport athletes. Previous authors have shown that plantar loading varies with footwear, sex, and the athletic task. Objective: To examine the effects of shoe type and sex on plantar loading in the medial midfoot (MMF), lateral midfoot (LMF), medial forefoot (MFF), middle forefoot (MidFF), and lateral forefoot (LFF) during a jump-landing task. Design: Crossover study. Setting: Laboratory. Patients or Other Participants: Twenty-seven recreational athletes (14 men, 13 women) with no history of lower extremity injury in the last 6 months and no history of foot or ankle surgery. Main Outcome Measure(s): The athletes completed 7 jumping trials while wearing bladed-cleat, turf-cleat, and running shoes. Maximum force, contact area, contact time, and the force-time integral were analyzed in each foot region. We calculated 2 × 3 analyses of variance (α = .05) to identify shoe-condition and sex differences. Results: We found no shoe × sex interactions, but the MMF, LMF, MFF, and LFF force-time integrals were greater in men (P < .03). The MMF maximum force was less with the bladed-cleat shoes (P = .02). Total foot and MidFF maximum force was less with the running shoes (P < .01). The MFF and LFF maximum forces were different among all shoe conditions (P < .01). Total foot contact area was less in the bladed-cleat shoes (P = .01). The MMF contact area was greatest in the running shoes (P < .01). The LFF contact area was less in the running shoes (P = .03). The MFF and LFF force-time integrals were greater with the bladed-cleat shoes (P < .01). The MidFF force-time integral was less in the running shoes (P < .01). Conclusions: Independent of shoe, men and women loaded the foot differently during a jump landing. The bladed cleat increased forefoot loading, which may increase the risk for forefoot injury. The type of shoe should be considered when choosing footwear for athletes returning to activity after metatarsal stress fractures.
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Fischer, Aryeh, Kevin K. Brown, Roland M. Du Bois, Stephen K. Frankel, Gregory P. Cosgrove, Evans R. Fernandez-Perez, Tristan J. Huie, et al. "Mycophenolate Mofetil Improves Lung Function in Connective Tissue Disease-associated Interstitial Lung Disease." Journal of Rheumatology 40, no. 5 (March 1, 2013): 640–46. http://dx.doi.org/10.3899/jrheum.121043.
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Objective.Small series suggest mycophenolate mofetil (MMF) is well tolerated and may be an effective therapy for connective tissue disease-associated interstitial lung disease (CTD-ILD). We examined the tolerability and longitudinal changes in pulmonary physiology in a large and diverse cohort of patients with CTD-ILD treated with MMF.Methods.We identified consecutive patients evaluated at our center between January 2008 and January 2011 and prescribed MMF for CTD-ILD. We assessed safety and tolerability of MMF and used longitudinal data analyses to examine changes in pulmonary physiology over time, before and after initiation of MMF.Results.We identified 125 subjects treated with MMF for a median 897 days. MMF was discontinued in 13 subjects. MMF was associated with significant improvements in estimated percentage of predicted forced vital capacity (FVC%) from MMF initiation to 52, 104, and 156 weeks (4.9% ± 1.9%, p = 0.01; 6.1% ± 1.8%, p = 0.0008; and 7.3% ± 2.6%, p = 0.004, respectively); and in estimated percentage predicted diffusing capacity (DLCO%) from MMF initiation to 52 and 104 weeks (6.3% ± 2.8%, p = 0.02; 7.1% ± 2.8%, p = 0.01). In the subgroup without usual interstitial pneumonia (UIP)-pattern injury, MMF significantly improved FVC% and DLCO%, and in the subgroup with UIP-pattern injury, MMF was associated with stability in FVC% and DLCO%.Conclusion.In a large diverse cohort of CTD-ILD, MMF was well tolerated and had a low rate of discontinuation. Treatment with MMF was associated with either stable or improved pulmonary physiology over a median 2.5 years of followup. MMF appears to be a promising therapy for the spectrum of CTD-ILD.
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Yang, Fan, Liqiang Zhang, Chenglin Bai, Shijie Ren, Zhen Tian, Yicun Yao, and Minghong Wang. "Yb-Doped Mode-Locked Fiber Laser Based on an All-Fiber Interferometer Filter." Photonics 10, no. 2 (February 13, 2023): 203. http://dx.doi.org/10.3390/photonics10020203.
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An interference filter is designed by fusing a segment of multi-core fiber (MCF) between two segments of multimode fibers (MMFs), which is then spliced between two segments of single mode fibers (SMFs). The light is split into the cladding and different cores of the MCF through the first segment of MMF, which is then coupled back into the core of SMF by the second segment of MMF. When the lengths of MCF are selected to be 4 mm and 10 mm, the 3 dB bandwidths of the filters around 1060 nm are 8.40 nm and 4.84 nm, respectively. Applying these filters in an Yb-doped fiber laser mode-locked by nonlinear polarization rotation, stable pulses have been obtained. Compared with the reported interference filters, the filter proposed in this paper has the advantages of simple fabrication process, compact structure and high environmental stability.
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Van Bruggen, M. C., B. Walgreen, T. P. Rijke, and J. H. Berden. "Attenuation of murine lupus nephritis by mycophenolate mofetil." Journal of the American Society of Nephrology 9, no. 8 (August 1998): 1407–15. http://dx.doi.org/10.1681/asn.v981407.
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Mycophenolate mofetil (MMF) is the morpholinoethyl ester of mycophenolic acid, which is its active metabolite. MMF is effective in prolonging survival of allografts and xenografts. However, little is known about the effects and the main mechanism of action of MMF in autoimmune diseases. In this study, the effect of MMF on the spontaneous disease progression in the MRL/lpr mouse model of lupus was examined. Eight-week-old MRL/lpr mice (n=18) were orally treated with MMF dissolved in a vehicle (90 mg/kg) once a day. Control animals received vehicle alone (n=17). The incidence of albuminuria (>300 microg/18 h) was significantly reduced by MMF treatment compared with vehicle-treated controls (cumulative incidence of albuminuria at 23 wk in MMF-treated mice; 22% versus 88% in controls; P=0.0001). The glomerulonephritis was histologically less severe in MMF-treated mice than in control mice (P=0.005). Furthermore, in immunofluorescence studies the amount of immunoglobulin and C3 deposits in the glomerular capillary wall was significantly less in MMF-treated mice (P < or = 0.002). Surprisingly, in vivo no clear-cut immune-modulating effects were observed because there were no differences between MMF-treated and control animals with regard to autoantibody formation. Also, spleen enlargement and numbers of CD3+, CD4+, and CD8+ T cells in spleen, lymph nodes, and peripheral blood were not different between both groups. Furthermore, no immunosuppressive properties of 90 mg/kg MMF were found in BALB/c mice on delayed-type hypersensitivity and primary antibody response to methylated bovine serum albumin. Interestingly, renal perfusion experiments revealed that binding of nucleosome/antinucleosome complexes to the glomerular basement membrane is decreased in MMF-treated mice compared with control mice. It is concluded that MMF suppresses the development of lupus glomerulonephritis and albuminuria in MRL/ lpr mice. The observed reduction of glomerular immunoglobulin deposits in MMF-treated mice and the renal perfusion studies indicate that MMF treatment leads to a decreased binding of immune complexes in the glomerular capillary wall in lupus nephritis.
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Seo, Jung-Woo, Yang Gyun Kim, Sang Ho Lee, Arah Lee, Dong-Jin Kim, Kyung-Hwan Jeong, Kyung Hye Lee, et al. "Mycophenolate Mofetil Ameliorates Diabetic Nephropathy in db/db Mice." BioMed Research International 2015 (2015): 1–11. http://dx.doi.org/10.1155/2015/301627.
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Chronic low-grade inflammation is an important factor in the pathogenesis of diabetic complication. Mycophenolate mofetil (MMF) has an anti-inflammatory effect, inhibiting lymphocyte proliferation. Previous studies showed attenuation of diabetic nephropathy with MMF, but the underlying mechanisms were unclear. This study aimed to identify the effect of MMF on diabetic nephropathy and investigate its action mechanisms in type 2 diabetic mice model. Eight-week-old db/db and control mice (db/m mice) received vehicle or MMF at a dose of 30 mg/kg/day for 12 weeks. MMF-treated diabetic mice showed decreased albuminuria, attenuated mesangial expansion, and profibrotic mRNA expressions despite the high glucose level. The number of infiltrated CD4+ and CD8+ T cells in the kidney was significantly decreased in MMF-treated db/db mice and it resulted in attenuating elevated intrarenal TNF-α and IL-17. The renal chemokines expression and macrophages infiltration were also attenuated by MMF treatment. The decreased expression of glomerular nephrin and WT1 was recovered with MMF treatment. MMF prevented the progression of diabetic nephropathy in db/db mice independent of glycemic control. These results suggest that the effects of MMF in diabetic nephropathy are mediated by CD4+ T cell regulation and related cytokines.
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Ferjani, H., A. Achour, H. Bacha, and S. Abid. "Tacrolimus and mycophenolate mofetil associations." Human & Experimental Toxicology 34, no. 11 (February 2, 2015): 1119–32. http://dx.doi.org/10.1177/0960327115569812.
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Gastrointestinal risk factors after organ transplantation are prevalent, due to the chronic use of immunosuppressant. The immunosuppressive drugs such as tacrolimus/mycophenolate mofetil (TAC/MMF) association are the most commonly used therapy. TAC and MMF have been implicated in gastrotoxicity, but their direct effects, alone and combined, on intestinal cells are not completely elucidated. This study investigated the effect of TAC and MMF alone and combined on human colon carcinoma cells. Our results demonstrated that TAC and MMF individually inhibit clearly cells proliferation, enhanced free radicals, lipid peroxidation production, induced DNA lesions and reduced mitochondrial membrane potential. In this study, we also showed that the two molecules TAC and MMF combined at high concentrations amplified the cell damage. Furthermore, the TAC (5 µM) prevented cell death induced by MMF (half maximal inhibitory concentration (IC50)). Also, MMF (50 µM) induced cytoprotection in HCT116 cells against TAC (IC50) toxicity. Our findings provide additional evidence that oxidative damage is the major contribution of TAC and MMF combined toxicities. In fact, MMF and TAC exert a gastroprotective effect by modulating reactive oxygen species production. These data underscore the pleiotropic effect of TAC and MMF on HCT116 cells that play a preventive and critical role on intestinal function.
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Atmakusuma, Tubagus Djumhana, and Fransiska Hardi. "The Role Of Mycophenolate Mofetil In Patients With Refractory ITP." Blood 122, no. 21 (November 15, 2013): 4756. http://dx.doi.org/10.1182/blood.v122.21.4756.4756.
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Background Referring to the ASH 2011 Guideline for ITP, several immune suppression agents are considered off-label use due to insufficient data for any specific agent to be recommended. In Indonesia mycophenolate mofetil (MMF) has been used as an alternative in ITP patients who failed to any recommended treatment in the ASH 2011 Guideline. Methods A retrospective study has been conducted to review data of ITP patients in three hospitals in Jakarta Indonesia. All ITP patients have been excluded from any potential causes of thrombocytopenia, including anamnesis, physical examination and laboratory tests for SLE, hepatitis C, hepatitis B and HIV. Results 52 ITP patients have been assessed which comprised 38 female (73,1 %) and 14 male (26.9%) with mean age 36.31 years old (ranged between 18 to 67 years old).13 of 52 patients have received MMF. 8 of 13 patients received MMF after failure to prednisone, 3 of 13 patients received MMF after failure to prednisone and azathioprine, 1 of 13 patients received MMF after failure to prednisone, then received thrombopoietin receptor agonist. Mean platelet count at diagnosed was 28.211/µL (ranged between 1,000 to 86,000/µL). 6 of 13 patients achieved good response (increased platelet count > 100,000/µ) and 3 of 13 patients achieved intermediate response (increased platelet count > 30,000 to < 100,000/µL). 4 other patients had no response to MMF (platelet count remained < 30,000/µL) in whom 1 patient has previously received prednisone, followed by MMF, 1 patient has previously received prednisone, then azathioprine, followed by MMF, 1 patient has previously received prednisone, then azathioprine , subsequently MMF followed by vincristine, and 1 patient has previously received prednisone, then azathiprone, subsequently MMF followed by eltrombopage. Conclusion 9 of 13 patients (almost 70 %) have responded to MMF. The remaining 30 % had no response to MMF. Disclosures: Off Label Use: Mycophenolate mofetil.
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Silva, H. T., H. C. Yang, M. Abouljoud, P. C. Kuo, K. Wisemandle, P. Bhattacharya, S. Dhadda, J. Holman, W. Fitzsimmons, and M. Roy First. "One-Year Results with Extended-Release Tacrolimus/MMF, Tacrolimus/MMF and Cyclosporine/MMF in De Novo Kidney Transplant Recipients." American Journal of Transplantation 7, no. 3 (March 2007): 595–608. http://dx.doi.org/10.1111/j.1600-6143.2007.01661.x.
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Amnuaikit, Thanaporn, Chalermkiat Songkram, and Sirirat Pinsuwan. "Enhancement of Mycophenolate Mofetil Permeation for Topical Use by Eucalyptol and N-Methyl-2-pyrrolidone." Scientifica 2016 (2016): 1–10. http://dx.doi.org/10.1155/2016/9672718.
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Mycophenolate mofetil (MMF) is a prodrug of mycophenolic acid (MPA) which can be metabolized by esterase. MMF has been approved by the United States Food and Drug Administration (USFDA) for treatment of psoriasis patient with skin symptoms. However, it remains unclear whether MMF is efficiently effective to treat skin symptoms developed from psoriasis. The insufficient amount of MMF penetrating through the skin results in the treatment failure due to the difficulty in MMF penetration through the stratum corneum. Skin permeation enhancers such as eucalyptol (EUL) and N-methyl-2-pyrrolidone (NMP) potentially aid in increasing skin penetration. This study aimed to investigate the effects of a concentration ratio (% w/v) between two enhancers (EUL and NMP). The results showed that EUL enhanced MMF permeation with an enhancement ratio (ER) of 3.44 while NMP was not able to promote the penetration of MMF. Interestingly, the synergistic effect of the two enhancers was observed with a suitable ratio given that the ER was 8.21. EUL and NMP are promising enhancers for the development of MMF based skin product.
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Hernandez Camba, A., L. Arranz, I. Vera, D. Carpio, M. Calafat Sard, A. Lucendo, C. Taxonera, et al. "P584 Use of mycophenolate mofetil in inflammatory bowel disease: results from the ENEIDA registry." Journal of Crohn's and Colitis 14, Supplement_1 (January 2020): S489—S490. http://dx.doi.org/10.1093/ecco-jcc/jjz203.712.
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Abstract Background Mycophenolate mofetil (MMF) is an immunomodulatory drug that inhibits T and B cells, through a reversible inhibition of inositol monophosphate dehydrogenase. MMF is commonly used for prophylaxis of organ rejection after transplant. Studies to evaluate its use in inflammatory bowel disease (IBD) are limited especially after the appearance of biological treatments (BT). The aim of this study was to evaluate the efficacy and safety of MMF in IBD. Methods IBD patients who had received MMF were identified in the ENEIDA registry (prospective database of GETECCU). Patients with Crohn′s disease (CD) or Ulcerative colitis (UC) in whom oral MMF was prescribed for this condition were evaluated. Demographic and IBD clinical data were collected. Clinical activity was assessed through Harvey-Bradshaw Index (HBI) and partial Mayo score (pMS); C-reactive protein (CRP) and faecal calprotectin (FC) were reviewed at baseline (at MMF starting), 3 and 6 months and at the end of follow-up (at MMF stopping or the last visit while on MMF). Adverse events (AEs) during MMF treatment were documented. Statistical analyses were performed by descriptive statistics and non-parametric tests. Results Between June 1999 and November 2018 a total of 83 patients received MMF (mean age 36.4 (SD12.3) years; 52F/31M; 66 CD and 17 UC). Indication for MMF use was maintenance of remission (50%), induction of remission (44%) and post-surgical prophylaxis (6%). Mean MMF dose used was 1269.8 (SD 741) mg/day. In 61% of cases, systemic steroids were administered starting MMF and it was used concomitantly to BT in 27% of patients. In CD, statistically significant differences in HBI at 6 months (mean 5.9 (SD 4.8), p = 0.04) and at the end of follow-up (mean 5.7 (SD 5), p = 0.014) compared with baseline (mean 7.6 (SD 4.3)) were observed. In UC, statistically significant differences in pMS at 6 months (mean 2.1 (SD 2.7), p = 0.018) and at the end of follow-up (mean 1.8 (SD 2.6), p = 0.003) compared with baseline (mean 4.8 (SD 2.5)) were determined. No significant differences in CRP or CF values during follow-up were observed. Concomitant use of BT was significantly associated with clinical response (OR 1.36 95% CI 1.08–1.73). MMF was maintained for a median time of 28.9 months (IQR 20.4–37.5) and was stopped in 84% of patients due to lack of response (50%), loss of response (17%) and remission (15%). Overall, 23% of patients presented MMF-related AEs (60% abdominal pain). MMF was withdrawn in 11% of patients due to AEs. Conclusion MMFshows a clinical benefit in the long term in both CD and UC patients with a favourable safety profile. MMF could be a treatment option alone or in combination with biologics in patients with IBD in clinical practice.
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Goyal, Abhinav, Moiz Salahuddin, and Yogesh Govil. "A Unique Case of Mycophenolate Induced Colitis after 10 Years of Use." Case Reports in Gastrointestinal Medicine 2016 (2016): 1–3. http://dx.doi.org/10.1155/2016/3058407.
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A 31-year-old female with a history of lupus nephritis on Hydroxychloroquine, Prednisone, and Mycophenolate Mofetil (MMF) for 10 years presented to the hospital for ankle swelling. On day four, she started to have severe, nonbloody, watery diarrhea with abdominal distension and tenderness. Stool PCR was negative forC. difficile.CT abdomen/pelvis showed gaseous distension of the colon without any obstruction. Flexible sigmoidoscopy revealed a normal looking mucosa. Histopathology showed crypt atrophy and increased crypt apoptosis, consistent with MMF colitis. The diarrhea resolved three days after stopping MMF. Although generally well tolerated, diarrhea is a common side effect of MMF. Most cases occur in the first six months of starting MMF. This case is unique because it describes MMF colitis in lupus after more than 10 years. Thus, MMF colitis should be considered as a differential in patients taking it, regardless of the duration of use.
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Satou, Ryousuke, Martha Franco, Courtney M. Dugas, Akemi Katsurada, and L. Gabriel Navar. "Immunosuppression by Mycophenolate Mofetil Mitigates Intrarenal Angiotensinogen Augmentation in Angiotensin II-Dependent Hypertension." International Journal of Molecular Sciences 23, no. 14 (July 12, 2022): 7680. http://dx.doi.org/10.3390/ijms23147680.
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Augmentation of intrarenal angiotensinogen (AGT) leads to further formation of intrarenal angiotensin II (Ang II) and the development of hypertensive kidney injury. Recent studies demonstrated that macrophages and the enhanced production of pro-inflammatory cytokines can be crucial mediators of renal AGT augmentation in hypertension. Accordingly, this study investigated the effects of immunosuppression by mycophenolate mofetil (MMF) on intrarenal AGT augmentation. Ang II (80 ng/min) was infused with or without daily administration of MMF (50 mg/kg) to Sprague-Dawley rats for 2 weeks. Mean arterial pressure (MAP) in Ang II infused rats was slightly higher (169.7 ± 6.1 mmHg) than the Ang II + MMF group (154.7 ± 2.0 mmHg), but was not statistically different from the Ang II + MMF group. MMF treatment suppressed Ang II-induced renal macrophages and IL-6 elevation. Augmentation of urinary AGT by Ang II infusion was attenuated by MMF treatment (control: 89.3 ± 25.2, Ang II: 1194 ± 305.1, and Ang II + MMF: 389 ± 192.0 ng/day). The augmentation of urinary AGT by Ang II infusion was observed before the onset of proteinuria. Elevated intrarenal AGT mRNA and protein levels in Ang II infused rats were also normalized by the MMF treatment (AGT mRNA, Ang II: 2.5 ± 0.2 and Ang II + MMF: 1.5 ± 0.1, ratio to control). Ang II-induced proteinuria, mesangial expansion and renal tubulointerstitial fibrosis were attenuated by MMF. Furthermore, MMF treatment attenuated the augmentation of intrarenal NLRP3 mRNA, a component of inflammasome. These results indicate that stimulated cytokine production in macrophages contributes to intrarenal AGT augmentation in Ang II-dependent hypertension, which leads to the development of kidney injury.
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Dhakal, Prajwal, Rakesh Gami, Smith Giri, and Vijaya R. Bhatt. "Mycophenolate Mofetil (MMF)-Induced Colitis." Blood 128, no. 22 (December 2, 2016): 4795. http://dx.doi.org/10.1182/blood.v128.22.4795.4795.
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Abstract Introduction MMF is an immunosuppressive drug frequently used for graft-versus-host disease (GVHD) prophylaxis and management. MMF-induced colitis is a known complication, however, details regarding its clinical manifestations, treatment options, and outcomes are less clear. Differentiating MMF-induced colitis from gut GVHD on the basis of histology may be difficult, hence deeper clinical understanding of MMF-induced colitis can be valuable. The aim of this systematic review was to analyze the reported cases of MMF-induced colitis to provide summative data. Methods Inclusion criteria included prospective or retrospective clinical studies and case series, reported in English language, providing data on clinical manifestations, treatment options, and outcomes of colitis induced by MMF or its derivatives (such as mycophenolic acid, and enteric coated mycophenolate sodium). Cases were included irrespective of the indication of MMF. Using various search terms, all cases indexed in PubMed, EMBASE, Cochrane and Scopus from inception to July 2016 were reviewed. The bibliography of each relevant article was searched for additional reports. Non-human studies and colitis attributed to other etiologies such as infection, GVHD or inflammatory bowel disease were among the 138 articles that were excluded. Results Forty-four articles with a total of 544 patients and 560 episodes of suspected or confirmed MMF-induced colitis were included. The median age was 41 years (range 5-70), and 30% were females. The latency between the use of MMF and onset of colitis was 990 days (range 3- 5760). Watery diarrhea as frequent as every 20 minutes in one case and large volume at times, was the presenting symptom in 92% of cases. Other less common presentations included bloody diarrhea, abdominal pain, and steatorrhea. MMF was discontinued or dose reduced in 65%, switched to enteric coated mycophenolate mofetil sodium in 14% and continued in 21% of cases. Ninety-eight percent of cases managed with discontinuation or dose reduction of MMF responded to the treatment. About 93% of cases who switched from MMF to enteric coated mycophenolate mofetil sodium responded. Among the patients who continued MMF, diarrhea was persistent in 17% while it resolved spontaneously in 83% (Figure 1). The median time to response to either change to enteric coated mycophenolate sodium or discontinuation of treatment was 20 days (range 1-45). Complications developed in 3.5% (n=19) of cases including graft rejection in solid-organ transplant (n=11) after discontinuation or dose reduction of MMF, acute dehydration (n=6), toxic colitis (n=1), and severe weight loss of >60 pounds (n=1). Conclusion MMF-induced colitis generally presents with watery diarrhea but rarely blood may be noted in stool. The latency period can be as long as months to years, hence a long latency period does not exclude the possibility. A vast majority of patients respond to cessation of MMF or dose reduction within a few weeks, however, cessation of MMF may result in graft rejection. In cases where continuation of immunosuppressive therapy is considered important to prevent graft rejection, alternate management option for management of MMF-induced colitis could include switching to a different drug formulation. Figure 1 Management and outcomes of MMF-induced colitis Figure 1. Management and outcomes of MMF-induced colitis Disclosures No relevant conflicts of interest to declare.
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Devlin, Shane M., Mark G. Swain, Stefan J. Urbanski, and Kelly W. Burak. "Mycophenolate Mofetil for the Treatment of Autoimmune Hepatitis in Patients Refractory to Standard Therapy." Canadian Journal of Gastroenterology 18, no. 5 (2004): 321–26. http://dx.doi.org/10.1155/2004/504591.
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There are limited therapeutic options available for patients with autoimmune hepatitis in whom conventional treatment fails. A case series of five patients unresponsive to or unable to take azathioprine, 6-mercaptopurine or corticosteroids who were treated with mycophenolate mofetil (MMF) is reported. While on MMF, alanine aminotransferase normalized or remained normal in all patients. MMF had a steroid-sparing effect and histological remission was demonstrated in one patient after seven months of MMF. One patient experienced an uncomplicated episode of pyelonephritis. In conclusion, MMF can effectively induce and maintain remission in refractory autoimmune hepatitis patients.
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Papadopoulos, Nikolaos G., Theodor A. Balan, Liandre F. van der Merwe, Wei Wei Pang, Louise J. Michaelis, Lynette P. Shek, Yvan Vandenplas, Oon Hoe Teoh, Alessandro G. Fiocchi, and Yap Seng Chong. "Mixed Milk Feeding: A New Approach to Describe Feeding Patterns in the First Year of Life Based on Individual Participant Data from Two Randomised Controlled Trials." Nutrients 14, no. 11 (May 24, 2022): 2190. http://dx.doi.org/10.3390/nu14112190.
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‘Mixed Milk Feeding’ (MMF), whereby infants are fed with both breastmilk and infant formula during the same period, is a common feeding practice. Despite its high prevalence, knowledge regarding MMF practices and their association with (health) outcomes is limited, potentially because MMF behaviours are highly variable and difficult to standardise longitudinally. In this paper, we applied a statistical clustering algorithm on individual infant feeding data collected over the first year of life from two clinical trials: ‘TEMPO’ (n = 855) and ‘Venus’ (n = 539); these studies were conducted in different years and world regions. In TEMPO, more than half of infants were MMF. Four distinct MMF clusters were identified: early exclusive formula feeding (32%), later exclusive formula feeding (25%), long-term MMF (21%), and mostly breastfeeding (22%). The same method applied to ‘Venus’ resulted in comparable clusters, building trust in the robustness of the cluster approach. These results demonstrate that distinct MMF patterns can be identified, which may be applicable to diverse populations. These insights could support the design of future research studying the impact of infant feeding patterns on health outcomes. To standardise this in future research, it is important to establish a unified definition of MMF.
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Robles-Vera, Iñaki, Néstor de la Visitación, Manuel Sánchez, Manuel Gómez-Guzmán, Rosario Jiménez, Javier Moleón, Cristina González-Correa, et al. "Mycophenolate Improves Brain–Gut Axis Inducing Remodeling of Gut Microbiota in DOCA-Salt Hypertensive Rats." Antioxidants 9, no. 12 (November 28, 2020): 1199. http://dx.doi.org/10.3390/antiox9121199.
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Microbiota is involved in the host blood pressure (BP) regulation. The immunosuppressive drug mofetil mycophenolate (MMF) ameliorates hypertension. The present study analyzed whether MMF improves dysbiosis in mineralocorticoid-induced hypertension. Male Wistar rats were assigned to three groups: untreated (CTR), deoxycorticosterone acetate (DOCA)-salt, and DOCA treated with MMF for 4 weeks. MMF treatment reduced systolic BP, improved endothelial dysfunction, and reduced oxidative stress and inflammation in aorta. A clear separation in the gut bacterial community between CTR and DOCA groups was found, whereas the cluster belonging to DOCA-MMF group was found to be intermixed. No changes were found at the phylum level among all experimental groups. MMF restored the elevation in lactate-producing bacteria found in DOCA-salt joined to an increase in the acetate-producing bacteria. MMF restored the percentage of anaerobic bacteria in the DOCA-salt group to values similar to control rats. The improvement of gut dysbiosis was associated with an enhanced colonic integrity and a decreased sympathetic drive in the gut. MMF inhibited neuroinflammation in the paraventricular nuclei in the hypothalamus. This study demonstrates for the first time that MMF reduces gut dysbiosis in DOCA-salt hypertension models. This effect seems to be related to its capacity to improve gut integrity due to reduced sympathetic drive in the gut associated with reduced brain neuroinflammation.
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Karunamoorthy, Saravanakumar, Dineshkumar Thanigachalam, Dhanapriya Jeyachandran, Sakthirajan Ramanathan, Gopalakrishnan Natarajan, and Balasubramaniam Thoppalan. "The safety and efficacy of mycophenolate mofetil in children and adolescents with steroid-dependent nephrotic syndrome: a single-centre study." Clinical Kidney Journal 13, no. 2 (June 6, 2019): 179–83. http://dx.doi.org/10.1093/ckj/sfz061.
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Abstract Background Steroid-dependent nephrotic syndrome (SDNS) patients experience frequent relapse or adverse effects on long-term treatment with steroids or cyclophosphamide. This study assessed the efficacy and side effect profile of mycophenolate mofetil (MMF) therapy in children with nephrotic syndrome in our population. Methods A retrospective study was performed on children with SDNS who were on MMF therapy for a minimum period of 1 year, and were on regular follow-up in the Department of Nephrology at the Institute of Child Health and hospital for children attached to Madras Medical College. Results The study included 87 patients, with a male:female ratio of 2:1. The median age at diagnosis of nephrotic syndrome was 3 years [95% confidence interval (CI): 1–8 years], which was found to be a statistically significant risk factor for MMF failure. The median duration of follow-up after initiation of MMF therapy was 3 years and 3 months (95% CI: 1 year and 3 months to 6 years and 6 months). At initial evaluation, 31 (36%) patients presented with SDNS while the remaining had frequently relapsing nephrotic syndrome progressing to SDNS. Intravenous cyclophosphamide was used as first-line therapy in 82 patients, of whom 24 patients had persistent proteinuria while the remaining 58 had attained remission for a median duration of 6 months. The median duration of treatment with MMF was 2 years and 6 months (95% CI: 1 year and 3 months to 4 years and 6 months). MMF was used at a mean dose of 28.5 mg/kg. Seventy-two (83%) patients were MMF-sensitive, and these patients had a reduction in mean prednisolone dose from 1.28 to 0.35 mg/kg (P < 0.05). Among the MMF-sensitive patients, 31 had stopped MMF after a minimum period of 2 years, following which they had a median remission period of 5 months (95% CI: 1–8 months). MMF failure occurred in 15 (17%) patients. Adverse events were documented in 19 (22%) patients. Conclusions Continuous MMF therapy achieved remission in 83% of patients. MMF was well tolerated in the study population and discontinuation of MMF resulted in 100% relapse.
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Zierhut, M., N. Stübiger, K. Siepmann, and CME Deuter. "MMF and eye disease." Lupus 14, no. 3_suppl (March 2005): 50–54. http://dx.doi.org/10.1191/0961203305lu2119oa.
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Immunosuppressive treatment has shown to be effective in various ocular inflammatory disorders. Factors limiting their use are the individual response and the rate of side effects. This report summarizes our knowledge about the use of mycophenolate mofetil (MMF) in the treatment of ocular cicatricial pemphigoid (OCP), uveitis, atopic keratoconjunctivitis (AKC), prevention of graft rejection after penetrating keratoplasty (PK) and scleritis. Controlled studies have been performed for prevention of graft rejection after PK, showing MMF as effective in the prevention of graft rejection as cyclosporine A. In experimental uveitis, MMF has been demonstrated to be highly effective in prevention of retinal destruction. A number of studies have now shown that MMF also seems effective in uveitis. There are also studies with smaller patient groups which point out the effectiveness of MMF in OCP, AKC, and scleritis. In most of the studies, the spectrum of side effects was small, compared to other immunosuppressives.
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Scano, Alessandro, Robert Mihai Mira, and Andrea d’Avella. "Mixed matrix factorization: a novel algorithm for the extraction of kinematic-muscular synergies." Journal of Neurophysiology 127, no. 2 (February 1, 2022): 529–47. http://dx.doi.org/10.1152/jn.00379.2021.
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The mixed matrix factorization (MMF) is a novel method for extracting kinematic-muscular synergies. The previous state of the art algorithm (NMFpn) factorizes separately positive and rectified negative waveforms; the MMF instead employs a gradient descent method to factorize from mixed kinematic unconstrained data and muscular non-negative data. MMF achieves perfect reconstruction on noiseless data, improving the NMFpn. MMF shows promising applicability on real data.
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Vermersch, P., T. Stojkovic, and J. De Seze. "Mycophenolate mofetil and neurological diseases." Lupus 14, no. 3_suppl (March 2005): 42–45. http://dx.doi.org/10.1191/0961203305lu2117oa.
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We describe experience with the use of mycophenolate mofetil (MMF) in neurological diseases. Although only small series of patients or case reports were described, MMF is promising in immunemediated neuromuscular disorders. MMF has been used for the treatment of polymyositis, chronic inflammatory demyelinating polyradiculoneuropathy, and multifocal motor neuropathy. These studies showed that MMF is well tolerated and may be useful in some patients. MMF can be effective alone but mainly as an adjuvant therapy by reducing steroid requirements or the frequency of infusions of IVIg. MMF has also been tested alone as a single drug treatment or in combination with immunomodulatory drugs in multiple sclerosis in open surveillance trials or in phase II studies. None of these studies have been designed to demonstrate a clinical efficacy but preliminary results are very promising.
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Lone, Parveen Akhter, Mohammed Israr ul Khaliq, Mandeep Sharma, Owais Ahmed Malik, and Bashir Ahmed Lone. "Weight Changes (in kg) in Mandible Fracture Patients After IMF: A Prospective Study." Traumaxilla 1, no. 1 (April 2019): 35–37. http://dx.doi.org/10.1177/2632327319882801.
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Background: This prospective study is done to assess weight loss due to maxillomandibular fixation (MMF) in patients who have undergone treatment for maxillofacial fractures. This fixation method is a closed reduction technique that can interfere with normal nutrition intake of solid and semisolid foods and thus can result in weight loss and malnutrition. Therefore, in this study we explain the degree and pattern of weight loss in patients treated with MMF. Materials and Methods: We treated 300 patients for 4 to 6 weeks of MMF. We measured and compared the weight before and after MMF. Results: The loss of weight was statistically significant ( P < .001) with MMF treatment. Conclusion: MMF caused mild to moderate malnutrition in some cases so protein diet was recommended to such patients post treatment.
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Warde, Nick. "MMF for juvenile dermatomyositis." Nature Reviews Rheumatology 6, no. 10 (September 30, 2010): 555. http://dx.doi.org/10.1038/nrrheum.2010.148.
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Zierhut, M., N. StüBiger, K. Siepmann, and CME Deuter. "MMF and Eye Disease." Lupus 14, no. 1_suppl (January 2005): 50–54. http://dx.doi.org/10.1177/096120330501400111.
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Zhang, Shuo, Xiang Li, Yue Liu, Wenhuan Chen, Huiwen Niu, Qi Yan, Shengjia Wang, et al. "A MMF-TSMF-MMF Structure Coated Magnetic Fluid for Magnetic Field Measurement." IEEE Photonics Technology Letters 33, no. 19 (October 1, 2021): 1105–8. http://dx.doi.org/10.1109/lpt.2021.3106146.
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MEIER-KRIESCHE, HERWIG-ULF, AKINLOLU O. OJO, ALAN B. LEICHTMAN, JEFFREY D. PUNCH, JULIE A. HANSON, DIANE M. CIBRIK, and BRUCE KAPLAN. "Effect of Mycophenolate Mofetil on Long-Term Outcomes in African American Renal Transplant Recipients." Journal of the American Society of Nephrology 11, no. 12 (December 2000): 2366–70. http://dx.doi.org/10.1681/asn.v11122366.
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Abstract. African American renal transplant recipients have poorer graft survival. A study using the United States Renal Data Registry documented an improvement in graft survival for patients who took mycophenolate mofetil (MMF) compared with azathioprine (AZA). This analysis did not address the impact of MMF on African American renal transplant recipients. The present study aimed to quantify potential beneficial effects of MMF therapy on long-term renal allograft survival in African Americans. With the use of the United States Renal Data Registry, all adult Caucasian and African American patients who had received a primary renal transplant between 1988 and 1997 were analyzed by Kaplan-Meier analysis and Cox proportional hazard models. Primary study end points were death with a functioning graft and graft failure censored for death. A total of 57,926 patients were studied. For African Americans, 3-yr patient survival was 96.3 versus 93.2% (P < 0.001) for MMF and AZA, respectively. Three-yr death-censored graft survival for African Americans was 85.8 versus 75.1% (P < 0.001) for MMF and AZA, respectively. For Caucasians, 3-yr patient survival was 97.3 versus 93.2% for MMF and AZA, respectively. Three-yr death-censored graft survival for Caucasians was 90.1 versus 86.4% (P < 0.001) for MMF and AZA, respectively. By multivariate analysis, MMF was associated with a significant reduction in the relative risk for all study end points in African Americans. MMF therapy is associated with both improved patient and death-censored graft survival in African American renal transplant recipients. This benefit is comparable to the benefit of MMF in Caucasian renal transplant recipients.
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Liu, Rui, Han Qi, Lin Guan, Hang Wu, Jing Liu, Xiaoya Li, Juan Huang, Ling Zhang, Yuan Zhou, and Jingjing Zhou. "Functional connectivity of the default mode network subsystems in patients with major depressive episodes with mixed features." General Psychiatry 35, no. 6 (December 2022): e100929. http://dx.doi.org/10.1136/gpsych-2022-100929.
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BackgroundThe neuroimaging mechanism of major depressive episodes with mixed features (MMF) is not clear.AimsThis study aimed to investigate the functional connectivity of the default mode network (DMN) subsystems among patients with MMF and patients with major depressive disorder without mixed features (MDDnoMF).MethodsThis study recruited 47 patients with MDDnoMFand 27 patients with MMF from Beijing Anding Hospital, Capital Medical University, between April 2021 and June 2022. Forty-five healthy controls (HCs) were recruited. All subjects underwent resting-state functional magnetic resonance imaging scanning and clinical assessments. Intranetwork and internetwork functional connectivity were computed in the DMN core subsystem, dorsal medial prefrontal cortex (dMPFC) subsystem and medial temporal lobe (MTL) subsystem. Analysis of covariance method was performed to compare the intranetwork and internetwork functional connectivity in the DMN subsystems among the MDDnoMF, MMF and HC groups.ResultsThe functional connectivity within the DMN core (F=6.32, pFDR=0.008) and MTL subsystems (F=4.45, pFDR=0.021) showed significant differences among the MDDnoMF, MMF and HC groups. Compared with the HC group, the patients with MDDnoMFand MMF had increased functional connectivity within the DMN MTL subsystem, and the patients with MMF also showed increased functional connectivity within the DMN core subsystem. Meanwhile, compared with the MDDnoMF, the patients with MMF had increased functional connectivity within the DMN core subsystem (mean difference (MDDnoMF−MMF)=−0.08, SE=0.04, p=0.048). However, no significant differences were found within the DMN dMPFC subsystem and all the internetwork functional connectivity.ConclusionsOur results indicated abnormal functional connectivity patterns of DMN subsystems in patients with MMF, findings potentially beneficial to deepen our understanding of MMF’s neural basis.
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Mazzola, Maria Antonietta, Radhika Raheja, Keren Regev, Vanessa Beynon, Felipe von Glehn, Anu Paul, Isabelle Pierre, Pia Kivisakk, Howard L. Weiner, and Roopali Gandhi. "Monomethyl fumarate treatment impairs maturation of human myeloid dendritic cells and their ability to activate T cells." Multiple Sclerosis Journal 25, no. 1 (November 6, 2017): 63–71. http://dx.doi.org/10.1177/1352458517740213.
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Background: Dimethyl fumarate (DMF) and its active metabolite monomethyl fumarate (MMF) effectively lead to reduction in disease relapses and active magnetic resonance imaging (MRI) lesions. DMF and MMF are known to be effective in modulating T- and B-cell responses; however, their effect on the phenotype and function of human myeloid dendritic cells (mDCs) is not fully understood. Objective: To investigate the role of MMF on human mDCs maturation and function. Methods: mDCs from healthy controls were isolated and cultured in vitro with MMF. The effect of MMF on mDC gene expression was determined by polymerase chain reaction (PCR) array after in vitro MMF treatment. The ability of mDCs to activate T cells was assessed by in vitro co-culture system. mDCs from DMF-treated multiple sclerosis (MS) patients were analyzed by flow cytometry and PCR. Results: MMF treatment induced a less mature phenotype of mDCs with reduced expression of major histocompatibility complex class II (MHC-II), co-stimulatory molecules CD86, CD40, CD83, and expression of nuclear factor κB (NF-κB) subunits RELA and RELB. mDCs from DMF-treated MS patients also showed the same immature phenotype. T cells co-cultured with MMF-treated mDCs showed reduced proliferation with decreased production of interferon gamma (IFN-γ), interleukin-17 (IL-17), and granulocyte-macrophage colony-stimulating factor (GM-CSF) compared to untreated cells. Conclusion: We report that MMF can modulate immune response by affecting human mDC function.
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Van Gurp, Eveline, Jesus Bustamante, Antonio Franco, Lionel Rostaing, Thomas Becker, Eric Rondeau, Zenon Czajkowski, et al. "Comparable Renal Function at 6 Months with Tacrolimus Combined with Fixed-Dose Sirolimus or MMF: Results of a Randomized Multicenter Trial in Renal Transplantation." Journal of Transplantation 2010 (2010): 1–10. http://dx.doi.org/10.1155/2010/731426.
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In a multicenter trial, renal transplant recipients were randomized to tacrolimus with fixed-dose sirolimus (Tac/SRL,N= 318) or tacrolimus with MMF (Tac/MMF,N= 316). Targeted tacrolimus trough levels were lower in the Tac/SRL group after day 14. The primary endpoint was renal function at 6 months using creatinine clearance (Cockcroft-Gault) and was comparable at 66.4 mL/min (SE 1.4) with Tac/SRL and at 65.2mL/min (SE 1.3) with Tac/MMF (completers). Biopsy-confirmed acute rejection was 15.1% (Tac/SRL) and 12.3% (Tac/MMF). In both groups, graft survival was 93% and patient survival was 99.0%. Premature withdrawal due to an adverse event was twice as high in the Tac/SRL group, 15.1% versus 6.3%. Hypercholesterolemia incidence was higher with Tac/SRL (P<.05) while CMV, leukopenia, and diarrhea incidences were higher with Tac/MMF (P<.05). The incidence of any antidiabetic treatment for>30consecutive days in previously nondiabetic patients was 17.8%, Tac/SRL, and 24.8%, Tac/MMF. Evaluation at 6 months showed comparable renal function using tacrolimus/sirolimus and tacrolimus/MMF regimens.
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Nishihori, Taiga, Joseph Pidala, Jongphil Kim, Marcie Tomblyn, and Claudio Anasetti. "Comparison of Sirolimus and Mycophenolate Mofetil As Salvage Treatment for Acute Graft-Versus-Host Disease." Blood 118, no. 21 (November 18, 2011): 4548. http://dx.doi.org/10.1182/blood.v118.21.4548.4548.
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Abstract Abstract 4548 Acute graft vs. host disease (aGVHD) refractory or dependent on glucocorticoid therapy is a major source of mortality following allogeneic hematopoietic cell transplantation (HCT). Comparative studies to evaluate the efficacy of available salvage immune suppressive agents are lacking. We retrospectively compared the efficacy of sirolimus (SIR) and mycophenolate mofetil (MMF) as salvage aGVHD therapy for glucocorticoid refractory, dependent or intolerant patients. Of 281 consecutive patients who received HCT at Moffitt Cancer Center from 07/2004 to 09/2009, we identified 84 patients who received tacrolimus/methotrexate (Tac/MTX) as GVHD prophylaxis, were treated with systemic glucocorticoids as first line therapy for acute GVHD grades 2–4, were refractory (n=72) or dependent (n=12) to glucocorticoids, and received second line GVHD treatment with MMF (n=56) or SIR (n=28). Patient demographics and treatment variables were similar between the two groups except for year of transplant, which was earlier for MMF. Median age of the entire group was 50 (range 17 – 68). Disease diagnoses included AML (n=27), NHL (n=14), MDS (n=12), ALL (n=9), CML (n=7), CLL (n=4), SAA (n=2), MPD (n=5), MM/PCL (n=3), and HL (n=1). Conditioning regimens were busulfan/fludarabine for 71, and other regimens for 13. Except for 1 bone marrow graft in each group, all received peripheral blood stem cells. Graft sources were from HLA-matched siblings (35), or 8/8 HLA-matched unrelated donors (49). Overall grade distribution of aGVHD at time of salvage for MMF vs. SIR was the following: grade 1 (13 vs. 2), grade 2 (31 vs. 16), grade 3 (9 vs. 5) and grade 4 (3 vs. 5). Median steroid dose at the time of salvage was 1 (range 0.17 – 2.28) mg/kg for MMF group and 1 (range 0.12 – 2.0) mg/kg for SIR group. Median time from steroid to salvage was 20 (range 1 – 208) days for MMF and 19 (range 1 – 275) days for SIR (p=0.84). Complete response (CR) rates following initiation of MMF or SIR did not significantly differ at the following time points: 1 week (MMF 30%, SIR 21%), 4 weeks (MMF 44%, SIR 46%), and 6 weeks (MMF 60%, SIR 58%). Overall response rates (ORR) also did not differ significantly: 1 week (MMF 57%, SIR 42%), 4 weeks (MMF 57%, SIR 77%), and 6 weeks (MMF 72%, SIR 75%). Flare or progression of aGVHD while on salvage regimen was noted in 50% (MMF) and 36% (SIR) of patients (p=0.64). Median overall survival from the time of salvage therapy for MMF vs. SIR did not significantly differ, 11.6 (95% CI 7.0 – 28.1) vs. 9.7 (95% CI 5.4 – 15.9) months, log-rank p = 0.88. These retrospective data suggest that MMF and SIR have comparable activity in the treatment of steroid refractory or dependent acute GVHD. Disclosures: No relevant conflicts of interest to declare.
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Kim, Joyce J., Ramzi H. Mulki, and Kavya M. Sebastian. "Recalcitrant Esophageal Stricture Secondary to Mycophenolate Mofetil." Case Reports in Gastrointestinal Medicine 2020 (November 23, 2020): 1–5. http://dx.doi.org/10.1155/2020/8817801.
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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.
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LASKARI, KATERINA, ATHANASIOS G. TZIOUFAS, ANNA ANTONIOU, and HARALAMPOS M. MOUTSOPOULOS. "Longterm Followup After Tapering Mycophenolate Mofetil During Maintenance Treatment for Proliferative Lupus Nephritis." Journal of Rheumatology 38, no. 7 (April 15, 2011): 1304–8. http://dx.doi.org/10.3899/jrheum.101249.
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Objective.To determine the timing for safe reduction of mycophenolate mofetil (MMF) dose during remission-maintenance therapy of proliferative lupus nephritis.Methods.The study population consisted of 44 patients evaluated retrospectively; MMF dose was empirically tapered in 18/44 patients until the latest observation.Results.Patients reducing MMF ≤ 18 months after remission/complete remission had a 6.8-fold/6.3-fold higher risk of relapse compared to those taking a stable dose (p = 0.001, p = 0.011, respectively). Reducing MMF later than 18 months was not associated with increased relapse rates.Conclusion.Reducing MMF > 1.5 years after remission/complete remission seems to warrant drug tapering without increased risk of disease flare in proliferative lupus nephritis.
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LIU, Wen-hu, Ni-na TANG, and Qi-dong ZHANG. "Could mycophenolate mofetil combined with benazapril delay tubulointerstitial fibrosis in 5/6 nephrectomized rats?" Chinese Medical Journal 122, no. 2 (January 2009): 199–204. http://dx.doi.org/10.3760/cma.j.issn.0366-6999.2009.02.017.
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Background It was reported that combination of mycophenolate mofetil (MMF) and enalapril could reduce proteinuria, improve renal function, and down-regulate diabetes-induced macrophage recruitment and expression of monocyte chemotactic protein 1 (MCP-1) and transforming growth factor β (TGF-β) in diabetic renal tissue. But there are no compelling data available for the combination of MMF and angiotensin converting enzyme inhibitor (ACEI) for suppressing tubulointerstitial fibrosis in chronic kidney diseases. The present study was to disclose the effect of MMF combined with benazapril on delaying tubulointerstitial fibrosis and its possible mechanisms in 5/6 nephrectomized rats. Methods Fifty male SD rats underwent 5/6 nephrectomy (5/6 NX) were randomized into the following groups: NX (5/6 nephrectomized rats, distilled water, n=10), MMF (MMF 20 mg·kg-1·d-1, p.o., n=10), Ben (benazepril 10 mg·kg-1·d-1, p.o., n=10), MMF/Ben (MMF 20 mg·kg-1·d-1, p.o., and benazapril 10 mg·kg-1·d-1, p.o., n=10). They were monitored for proteinuria and systolic blood pressure every two weeks. After 8 weeks of treatment, serum creatinine and blood urea nitrogen were assayed and pathological damage to the kidney were evaluated. Renal expression and serum levels of platelet-derived growth factor-BB (PDGF-BB), matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metaloproteinase-1 (TIMP-1) were detected by immunohistochemistry and ELISA methods. Results After 8 weeks of treatment, 24-hour proteinuria, serum creatinine and blood urea nitrogen were significantly lower in treated groups compared with the untreated rats. MMF and benazepril combination therapy had a greater effect than either drug alone. MMF alone had no effect on systolic blood pressure, but benazapril and MMF/benazapril could significantly reduce blood pressure. Rats that underwent 5/6 nephrectomy had greater tubulointerstitial inflammatory cell infiltration and collagen accumulation than sham-operated rats; all treatments, especially MMF/benazepril, ameliorated these effects. Tubules in 5/6 nephrectomized rats expressed higher levels of PDGF-BB and TIMP-1 and lower MMP-9 compared with sham-operated rats. MMF and benazepril similarly reversed these phenomenons and combination therapy almost completely restored the expression of these cytokines in renal tissue and their plasma concentration. Conclusions MMF, especially combined with benazepril, can reduce proteinuria, improve renal function, ameliorate tubulointerstitial fibrosis in 5/6 nephrectomized rats. These effects might be, in part, associated with down-regulation of PDGF-BB and TIMP-1, and MMP-9 up-regulation in renal tissues.
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Umemura, Yoshie, Wajd Al-Holou, Bernard Marini, Denise Leung, Michelle Kim, Sean Ferris, Larry Junck, et al. "CTNI-35. PHASE 0/1 TRIAL OF MYCOPHENOLATE MOFETIL COMBINED WITH CHEMORADIATION TO OVERCOME TREATMENT RESISTANCE IN NEWLY DIAGNOSED AND RECURRENT GLIOBLASTOMA BY TARGETING PURINE METABOLISM." Neuro-Oncology 24, Supplement_7 (November 1, 2022): vii79. http://dx.doi.org/10.1093/neuonc/noac209.300.
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Abstract BACKGROUND Purine metabolism promotes glioblastoma growth, stemness, invasiveness, and treatment resistance. The purine synthesis inhibitor, mycophenolate mofetil (MMF), improves radiation and temozolomide efficacy in preclinical glioblastoma models. This phase 0/1 trial (NCT04477200) aims to determine the maximum-tolerated dose of MMF combined with chemoradiation in glioblastoma. It also aims to quantify the levels of the active metabolite of MMF and the extent of purine synthesis inhibition in enhancing and non-enhancing tumor tissue. METHODS Key eligibility criteria are age ≥ 18 and KPS ≥ 60%. TITE-CRM dose-escalation is used for MMF dosing starting at 1000mg PO BID (range 500-2000mg BID). Thirty recurrent glioblastoma patients receive MMF one-week prior to and concurrently with re-irradiation (40.5 Gy in 15 fractions), with 28 days of dose-limiting toxicity (DLT) period. Thirty newly diagnosed glioblastoma patients receive MMF one-week prior to and concurrently with standard radiation with concurrent temozolomide and followed for 28 days for DLT1-period, then MMF is given days 0-5 of each adjuvant cyclic temozolomide using a separate dose-escalation with the first two cycles as the DLT2-period. In phase 0, eight recurrent glioblastoma patients receive MMF 500-2000mg PO BID one-week pre-operatively and tissues are analyzed using mass spectrometry. RESULTS Eighteen phase 1 subjects (11 recurrent, 7 new) have received study treatment with no DLT to date up to MMF 2000mg BID. Main toxicities are mild nausea, fatigue, and elevated liver enzymes. No notable study-related hematotoxicity nor opportunistic infection have been observed. The active metabolite of MMF accumulated to active concentrations in enhancing and non-enhancing tumor tissue and appeared to inhibit purine synthesis. CONCLUSION MMF combined with chemoradiation has been reasonably well tolerated in glioblastoma patients with preliminary evidence of intracranial target engagement of its active metabolite. This study will yield a recommended phase 2 dose and preliminary efficacy estimate for future randomized phase 2/3 trial.
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Desai, Yasin, Thomas Jaki, Michael W. Beresford, Thomas Burnett, Despina Eleftheriou, Heidi Jacobe, Valentina Leone, et al. "Prior elicitation of the efficacy and tolerability of Methotrexate and Mycophenolate Mofetil in Juvenile Localised Scleroderma." AMRC Open Research 3 (September 9, 2021): 20. http://dx.doi.org/10.12688/amrcopenres.13008.1.
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Background Evidence is lacking for safe and effective treatments for juvenile localised scleroderma (JLS). Methotrexate (MTX) is commonly used first line and mycophenolate mofetil (MMF) second line, despite a limited evidence base. A head to head trial of these two medications would provide data on relative efficacy and tolerability. However, a frequentist approach is difficult to deliver in JLS, because of the numbers needed to sufficiently power a trial. A Bayesian approach could be considered. Methods An international consensus meeting was convened including an elicitation exercise where opinion was sought on the relative efficacy and tolerability of MTX compared to MMF to produce prior distributions for a future Bayesian trial. Secondary aims were to achieve consensus agreement on critical aspects of a future trial. Results An international group of 12 clinical experts participated. Opinion suggested superior efficacy and tolerability of MMF compared to MTX; where most likely value of efficacy of MMF was 0.70 (95% confidence interval (CI) 0.34-0.90) and of MTX was 0.68 (95% CI 0.41-0.8). The most likely value of tolerability of MMF was 0.77 (95% CI 0.3-0.94) and of MTX was 0.62 (95% CI 0.32-0.84). The wider CI for MMF highlights that experts were less sure about relative efficacy and tolerability of MMF compared to MTX. Despite using a Bayesian approach, power calculations still produced a total sample size of 240 participants, reflecting the uncertainty amongst experts about the performance of MMF. Conclusions Key factors have been defined regarding the design of a future Bayesian approach clinical trial including elicitation of prior opinion of the efficacy and tolerability of MTX and MMF in JLS. Combining further efficacy data on MTX and MMF with prior opinion could potentially reduce the pre-trial uncertainty so that, when combined with smaller trial sample sizes a compelling evidence base is available.
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Azevedo, Luiz Sergio, Maria Cristina R. Castro, Flavio J. Paula, Luiz Estevam Ianhez, and Elias David-Neto. "Mycophenolate mofetil may protect against Pneumocystis carinii pneumonia in renal transplanted patients." Revista do Instituto de Medicina Tropical de São Paulo 47, no. 3 (June 2005): 143–45. http://dx.doi.org/10.1590/s0036-46652005000300005.
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Pneumocystis carinii pneumonia (PCP) is usually prevented in transplanted patients by prophylactic trimethoprim-sulfamethoxazol (TMS). Mycophenolate mofetil (MMF) has been shown to have a strong protective effect against PCP in rats. This effect is also suggested in humans by the absence of PCP in patients receiving MMF. After January 1998 MMF has been used with no TMS prophylaxis in renal transplanted patients. In azathioprine (AZA) treated patients TMS prophylaxis was maintained. The incidence of PCP was analyzed in both groups. Data were collected in order to have a minimum 6-month follow-up. Two hundred and seventy-two patients were eligible for analysis. No PCP occurred either in patients under MMF without TMS prophylaxis nor in patients under AZA. MMF may have an effective protective role against PCP as no patient under MMF, despite not receiving TMS coverage, developed PCP. A larger, controlled, trial is warranted to consolidate this information.
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Singh, Virendra, and Amrish Bhagol. "A New and Easy Technique of Maxillomandibular Fixation in Treatment of Mandibular Fractures." Craniomaxillofacial Trauma & Reconstruction 4, no. 3 (September 2011): 175–77. http://dx.doi.org/10.1055/s-0031-1286121.
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The present work evaluated the success of maxillomandibular fixation (MMF) by a new and simplified technique in management of minimally displaced mandibular fractures. A total of 20 patients who sustained various types of mandibular fractures were treated at the Government Dental College, Rohtak, India by a new MMF technique. The patients were evaluated by preoperative and postoperative radiography, and clinical testing was performed to assess the degree of tooth mobility adjacent to the site of MMF. The time required for MMF was also noted. Patient recovery was uneventful in all 20 cases, and the period of MMF ranged from 2 to 4 weeks (mean 21 days). The outcome was good. The mean time for performing MMF was 12 minutes (range, 10 to 15 minutes). It is a simple, quick, economical, and minimally invasive technique. Its mechanical principle provides an advantage in preventing postoperative periodontal problems.
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Dykes, Dana M. H., Sean R. Moore, D. Brent Polk, Michael J. Rosen, Marcia L. Wills, Brian Morris, Jeanine S. Maclin, et al. "Mycophenolate Mofetil-Related Enterocolitis and Weight Loss: A Pediatric Case Series." Case Reports in Pediatrics 2012 (2012): 1–5. http://dx.doi.org/10.1155/2012/624168.
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Mycophenolate mofetil (MMF) is an immunosuppressive medication utilized in the management of both autoimmune and solid organ transplant patients. Diarrhea is a common gastrointestinal side effect of MMF, but more severe forms of GI symptoms are described in renal transplant patients with a distinct pattern of histopathologic change, similar to graft-versus-host disease or Crohn’s disease. This rare entity, commonly referred to as “MMF-related enterocolitis,” has been described in adult patients, mostly in renal transplant patients, and in only two pediatric renal transplant patients. In previously reported cases, symptoms and abnormal histopathology improve with dose reduction of MMF. We describe a series of three pediatric patients with varied underlying disease process who presented with severe diarrhea and histopathologic findings characteristic of MMF-related enterocolitis, who share a novel finding of weight loss as a complication of MMF-related enterocolitis in pediatric patients.
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FUJIHARA, CLARICE KAZUE, IRENE DE LOURDES NORONHA, DENISE MARIA AVANCINI COSTA MALHEIROS, GLÁUCIA RUTIGLIANO ANTUNES, IVONE BRAGA DE OLIVEIRA, and ROBERTO ZATZ. "Combined Mycophenolate Mofetil and Losartan Therapy Arrests Established Injury in the Remnant Kidney." Journal of the American Society of Nephrology 11, no. 2 (February 2000): 283–90. http://dx.doi.org/10.1681/asn.v112283.
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Previously it was shown that early treatment with mycophenolate mofetil (MMF) attenuated renal inflammation, glomerulosclerosis (GS), and interstitial expansion in the 5/6 ablation (NX) model. Angiotensin II antagonists also mitigate renal injury in NX, presumably by lowering glomerular pressure (PGC). This study investigated: (1) whether combined MMF/angiotensin II antagonists treatment affords superior protection compared with the respective monotherapies; and (2) whether this association is effective even when instituted late in the course of the disease. Adult male Munich-Wistar rats underwent NX, remaining untreated for 30 d. BP, albuminuria, and the extent of GS, interstitial expansion, and macrophage infiltration were then determined in 17 rats. The remaining 118 rats received either inert vehicle or one of the following: MMF, 10 mg/kg by gavage once daily; losartan potassium (L), 20 mg/dl in drinking water; or combined MMF/L treatment. Sixty days after ablation, untreated NX rats exhibited marked glomerular hypertension, which was attenuated by MMF and, more effectively, by either L or combined MMF/L treatment. At 120 d, hypertension and albuminuria were worsened in untreated NX rats, which exhibited intense macrophage infiltration and severe glomerular and interstitial disease. L and, to a lesser extent, MMF monotherapies attenuated these abnormalities, without preventing their progression. In rats given combined MMF/L therapy, macrophage infiltration, GS, and interstitial expansion remained at pretreatment levels. By acting on two distinct pathogenic mechanisms, combined MMF/L treatment arrested established renal injury in the NX model. Further investigation is needed to determine whether this association can prevent renal scarring in other models and in human disease.
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Iijima, Kazumoto, Mayumi Sako, Mari Oba, Seiji Tanaka, Riku Hamada, Tomoyuki Sakai, Yoko Ohwada, et al. "Mycophenolate Mofetil after Rituximab for Childhood-Onset Complicated Frequently-Relapsing or Steroid-Dependent Nephrotic Syndrome." Journal of the American Society of Nephrology 33, no. 2 (December 8, 2021): 401–19. http://dx.doi.org/10.1681/asn.2021050643.
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BackgroundRituximab is the standard therapy for childhood-onset complicated frequently relapsing or steroid-dependent nephrotic syndrome (FRNS/SDNS). However, most patients redevelop FRNS/SDNS after peripheral B cell recovery.MethodsWe conducted a multicenter, randomized, double-blind, placebo-controlled trial to examine whether mycophenolate mofetil (MMF) administration after rituximab can prevent treatment failure (FRNS, SDNS, steroid resistance, or use of immunosuppressive agents or rituximab). In total, 39 patients (per group) were treated with rituximab, followed by either MMF or placebo until day 505 (treatment period). The primary outcome was time to treatment failure (TTF) throughout the treatment and follow-up periods (until day 505 for the last enrolled patient).ResultsTTFs were clinically but not statistically significantly longer among patients given MMF after rituximab than among patients receiving rituximab monotherapy (median, 784.0 versus 472.5 days, hazard ratio [HR], 0.59; 95% confidence interval [95% CI], 0.34 to 1.05, log-rank test: P=0.07). Because most patients in the MMF group presented with treatment failure after MMF discontinuation, we performed a post-hoc analysis limited to the treatment period and found that MMF after rituximab prolonged the TTF and decreased the risk of treatment failure by 80% (HR, 0.20; 95% CI, 0.08 to 0.50). Moreover, MMF after rituximab reduced the relapse rate and daily steroid dose during the treatment period by 74% and 57%, respectively. The frequency and severity of adverse events were similar in both groups.ConclusionsAdministration of MMF after rituximab may sufficiently prevent the development of treatment failure and is well tolerated, although the relapse-preventing effect disappears after MMF discontinuation.
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GOLDSMITH, David, Elizabeth A. CARREY, Stephen EDBURY, Ryszard T. SMOLENSKI, Piotr JAGODZINSKI, and H. Anne SIMMONDS. "Mycophenolate mofetil, an inhibitor of inosine monophosphate dehydrogenase, causes a paradoxical elevation of GTP in erythrocytes of renal transplant patients." Clinical Science 107, no. 1 (June 23, 2004): 63–68. http://dx.doi.org/10.1042/cs20030331.
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The immunosuppressant MMF (mycophenolate mofetil) has increasingly replaced AZA (azathioprine) in renal transplantation. MMF is a prodrug of MPA (mycophenolic acid), which inhibits lymphocyte IMPDH (inosine monophosphate dehydrogenase), thereby drastically decreasing GTP concentrations essential to lymphocyte proliferation in vitro and in vivo. Erythrocyte GTP concentrations are commonly elevated in severe renal disease, but normalize following successful engraftment. Consequently, elevated GTP in renal transplant recipients might signal impending loss of immunosuppression and graft failure. In the present study, we compared erythrocyte nucleotides and plasma metabolites in two groups of 25 patients after renal transplantation, both receiving prednisolone and cyclosporin A, but one group receiving MMF and the other AZA. No patients had recent allograft biopsy evidence of rejection. Erythrocyte GTP concentrations at MMF commencement were 50.4±23.4 μmol/l. An increase occurred during the first 3 months after transplant when MMF was used de novo, stabilizing at 146.7±62.9 μmol/l after 4 months. This was significantly higher (P=2.5×10−6) than erythrocyte GTP (40.4±15.9 μmol/l) in the AZA group, which was essentially unchanged from values immediately after successful transplantation. The effect of MMF on erythrocyte GTP levels was reversible, since GTP levels fell when MMF therapy was terminated. The results demonstrate paradoxically high GTP concentrations in erythrocytes of renal transplant patients receiving MMF. MPA may stabilize reticulocyte IMPDH, allowing the protein to persist during erythropoiesis. This behaviour is in marked contrast with the decrease in GTP levels seen in white blood cells of patients on chronic MMF therapy.
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Philobos, Mariana, Amy Perkins, Maira Karabayas, Paula Dospinescu, Nick Fluck, Dana Kidder, Fiona A. Chapman, Neeraj Dhaun, and Neil Basu. "A real-world assessment of mycophenolate mofetil for remission induction in eosinophilic granulomatosis with polyangiitis." Rheumatology International 41, no. 10 (August 4, 2021): 1811–14. http://dx.doi.org/10.1007/s00296-021-04961-w.
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AbstractEosinophilic granulomatosis with polyangiitis (EGPA) is a form of ANCA-associated vasculitis (AAV). Clinical trials demonstrating the efficacy of mycophenolate mofetil (MMF) for remission induction in AAV excluded patients with EGPA. Despite this, MMF is commonly used in these patients. The objective of this study was to evaluate, for the first time, the effectiveness and tolerance of MMF in EGPA remission induction. A retrospective, two-center, real-world study was conducted in patients with EGPA who received MMF in addition to prednisolone for newly diagnosed or relapsing disease between 2009 and 2019. Baseline, 3-, 6- and 12-month outcome data were extracted from electronic health records. The primary outcome was disease remission, defined as a Birmingham Vasculitis Activity Score of 0 at 6 months. Secondary outcomes included disease relapse, median prednisolone dose at 12 months and drug tolerance. In total, 15 patients (73% male, median age 57) with EGPA (11 newly diagnosed/4 relapsing) were identified. At 6 months, 67% had achieved disease remission. At 12 months, this was maintained (66.7%) and 4 patients had relapsed. All but one patient remained on MMF at study completion and all patients tolerated MMF. Our real-world data suggest that MMF is an effective and well-tolerated agent for achieving disease remission in EGPA. A future randomized controlled trial of MMF in this neglected orphan disease is now warranted.
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Jesus, D., M. Rodrigues, J. A. P. da Silva, and L. Inês. "Multitarget therapy of mycophenolate mofetil and cyclosporine A for induction treatment of refractory lupus nephritis." Lupus 27, no. 8 (February 15, 2018): 1358–62. http://dx.doi.org/10.1177/0961203318758508.
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Standard induction therapy for lupus nephritis (LN) with mycophenolate mofetil (MMF) or cyclophosphamide (CYC) is often ineffective. Evidence on rescue induction regimens is scarce. We analyzed efficacy and tolerability of multitarget immunosuppression with MMF and cyclosporine A (CsA) as induction treatment for LN (class III/IV/V) refractory to CYC and/or MMF. We included all six refractory LN patients (class IV = 3, class V = 2, class III = 1) from our 400-patient tertiary Lupus Clinic observed between 2012 and 2015. Four patients had previously received pulse CYC. All six received MMF as first or second induction therapy and CsA was added once failure to reach remission was established. Daily dose of MMF was 2–3 g and CsA was dosed up to 2.6–3.7 mg/kg/day. Mean proteinuria was reduced from 2407 mg/24 hours at the start of the MMF+CsA regimen to 544 mg/day after six months. The mean prednisolone dose was reduced from 17.5 to 6 mg/day after six months of MMF+CsA. Four patients achieved a complete renal response, one patient had a partial renal response and one failed to respond. None of the patients presented with adverse events. These data suggest that adding CsA to MMF can induce complete remission of refractory LN and is well tolerated.
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Allison, AC. "Mechanisms of action of mycophenolate mofetil." Lupus 14, no. 3_suppl (March 2005): 2–8. http://dx.doi.org/10.1191/0961203305lu2109oa.
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Mycophenolate mofetil (MMF, CellCept®) is a prodrug of mycophenolic acid (MPA), an inhibitor of inosine-5′-monophosphate dehydrogenase. MPA depletes guanosine nucleotides preferentially in T and B lymphocytes and inhibits their proliferation, thereby suppressing cell-mediated immune responses and antibody formation. MPA also inhibits the glycosylation and expression of adhesion molecules, and the recruitment of lymphocytes and monocytes into sites of inflammation. MPA depletes tetrahydrobiopterin and decreases the production of nitric oxide by inducible NO synthase without affecting the activity of constitutive NO synthases. Activated macrophages produce NO and superoxide, which combine to generate tissue-damaging peroxynitrite. By these two mechanisms MMF exerts anti-inflammatory activity. Unlike calcineurin inhibitors, MMF is not nephrotoxic and does not induce the production of TGF, which is fibrogenic. MMF does not increase blood pressure, cholesterol levels or triglyceride levels in recipients. MMF reduces acute and chronic rejection in allograft recipients and is efficacious in some nephropathies. Evidence is accumulating that MMF may have clinical utility in some autoimmune disorders.