Uso de micofenolato mofetilo fuera de registro en enfermedades inmunomediadas / Off-label use of mycophenolate mofetil in immune-mediated diseases

BACKGROUND: Mycophenolate mofetil (MMF) is a largely used immunosuppressive agent in the prevention of transplant rejection and lupus nephritis. Its use has been extended to other immune-mediated diseases (ID). AIM: To assess the off-label use of MMF, its performance as a glucocorticoid sparing agent, the therapeutic response, and its adverse effects. MATERIAL AND METHODS: A retrospective study was performed. One hundred-seven patients aged 58 ± 16 years (83% females) who received MMF for ID in off label uses between 2016 and 2018 were included. The study variables were cause of MMF indication, sex, age, use as a first- or second-line treatment and maintenance dosing. The cumulative doses of glucocorticoids six months before and after MMF indication were compared. RESULTS: MMF was used as a second-line therapy in 66 patients (62%). The mean maintenance dose of MMF was 1,500 ± 540 mg/day. Prednisone cumulative doses were 3,908 ± 2,173 and 1,672 ± 1,083 milligrams six months before and six months after starting MMF, respectively (p < 0.01). Adverse effects were identified in 21 (20%) cases, none of them serious. CONCLUSIONS: Mycophenolate has a favorable response profile as a second line immunosuppressive agent. It is effective as a glucocorticoid sparing drug. The safety profile is also favorable as adverse effects were scanty and mild.

[Off-label use of mycophenolate mofetil in immune-mediated diseases]. / Uso de micofenolato mofetilo fuera de registro en enfermedades inmunomediadas.

BACKGROUND: Mycophenolate mofetil (MMF) is a largely used immunosuppressive agent in the prevention of transplant rejection and lupus nephritis. Its use has been extended to other immune-mediated diseases (ID). AIM: To assess the off-label use of MMF, its performance as a glucocorticoid sparing agent, the therapeutic response, and its adverse effects. MATERIAL AND METHODS: A retrospective study was performed. One hundred-seven patients aged 58 ± 16 years (83% females) who received MMF for ID in off label uses between 2016 and 2018 were included. The study variables were cause of MMF indication, sex, age, use as a first- or second-line treatment and maintenance dosing. The cumulative doses of glucocorticoids six months before and after MMF indication were compared. RESULTS: MMF was used as a second-line therapy in 66 patients (62%). The mean maintenance dose of MMF was 1,500 ± 540 mg/day. Prednisone cumulative doses were 3,908 ± 2,173 and 1,672 ± 1,083 milligrams six months before and six months after starting MMF, respectively (p < 0.01). Adverse effects were identified in 21 (20%) cases, none of them serious. CONCLUSIONS: Mycophenolate has a favorable response profile as a second line immunosuppressive agent. It is effective as a glucocorticoid sparing drug. The safety profile is also favorable as adverse effects were scanty and mild.

The role of plant size in the selection of glyphosate resistance in Sorghum halepense.

BACKGROUND: The effect of plant size (seedlings versus young plants versus adult plants) on the phenotypic level of glyphosate resistance and selection intensity (SI) in Sorghum halepense with and without a reduced glyphosate translocation resistance mechanism was evaluated. RESULTS: Resistance parameters [the 50% lethal dose (LD50 ) and the dose required to cause a 50% reduction in plant growth (GR50 )] in adult plants were notably higher than in seedlings regardless of the resistance status. However, under similar plant size increases, populations comprised of glyphosate-resistant (R) individuals showed higher survival and growth when glyphosate treated compared with glyphosate-susceptible (S) plants. An increase in SI was always evident with increasing glyphosate doses. However, the rate of increase in SI was higher under glyphosate selection of young R and S plants, followed by seedlings and adult R and S plants. However, in conditions of R seedlings coexisting with adult S plants under glyphosate treatment (1000-4000 g ha-1 ), selection against glyphosate resistance was observed. CONCLUSION: Any increase in size from the seedling stage of R plants translates into an amplification of resistance. Depending on the particular size combinations of spatially coexisting R and S plants, selection for glyphosate resistance may be faster, slower or even not evident. © 2018 Society of Chemical Industry.

No escape? Costs and benefits of leaf de-submergence in the pasture grass Chloris gayana under different flooding regimes.

Elongation-induced leaf emergence is one way for plants to deal with complete submergence by 'escaping' from water. This growth strategy is hypothesised to be more beneficial under single long-term submergence than under repeated short-term submergence events (i.e. fluctuating environment), as costs of repeated plant 'adjustment' would exceed the initial benefits of shoot elongation. To test this idea, 2-week-old plants of Chloris gayana Kunth. cv. Fine Cut (a submergence-tolerant cultivar first selected by a screening experiment) were grown for 4 weeks under (i) control conditions, (ii) two 1-week submergence cycles, or (iii) one 2-week submergence cycle. Additionally, a set of plants were placed below nettings to assess the cost of remaining forcedly submerged. Impeding leaves emergence through nettings did not compromise survival when submergence was 1-week long, but determined the death of all plants when extended to 2 weeks. Growth as affected by flooding regime revealed that under one 2-week submergence event, plants accumulated a 2.9-fold higher dry mass than when they experienced the same submergence duration in separate events along 1week. The 'escape' strategy in the grass C. gayana, by which leaf contact with air is re-established, is essential for its survival, and it is more beneficial for plant growth under long-term submergence than under repeated short-term submergence cycles.

Phenomic networks reveal largely independent root and shoot adjustment in waterlogged plants of Lotus japonicus.

Waterlogging imposes severe stress to the plant, and the interplay between root and aerial organs in the adjustment to this stress is poorly understood. A set of recombinant inbred lines (RILs) of Lotus japonicus (Gifu B-129 × Miyakojima MG-20) was subjected to control and waterlogging conditions for 21 d, and 12 traits related to leaf physiological functioning, root aerenchyma formation, shoot and root morphology, and dry mass accumulation were assessed to generate phenomic networks. The phenomic network became more complex under waterlogging as a result of the incorporation of root aerenchyma and dark-adapted Fv/Fm. Significant waterlogging-induced variation was found for stomatal conductance, dark-adapted Fv/Fm and aerenchyma. The RILs with stronger induction of aerenchyma in response to waterlogging tended to show reduced negative impact of this stress on root growth but suffered average impact on shoot growth. The RILs that retained higher stomatal conductance under waterlogging tended to retain higher dark-adapted Fv/Fm and shoot growth under waterlogging conditions but showed average impact on root traits. We propose a model where, although the stress experienced by the roots during waterlogging is transmitted to the shoot, shoots and roots deal with waterlogging in a less interdependent manner than often assumed.