Background and ImportanceCyclosporine is an immunosuppressive drug with complex pharmacokinetics, a narrow therapeutic interval and dose-related adverse effects (nephrotoxicity, hepatotoxicity, and ...neurotoxicity).Amiodarone, verapamil and macrolides increase cyclosporine serum concentrations (CSC), whereas other drugs such as phenytoin, carbamazepine and rifampin decrease CSC.Therefore, therapeutic drug monitoring of cyclosporine is of great importance in routine clinical practice.Aim and ObjectivesDesign a population pharmacokinetic model of cyclosporine.Analyse the influence of the recorded covariates.Material and MethodsRetrospective observational study that included patients hospitalised at Severo Ochoa University Hospital and treated with cyclosporine between January 2016 and April 2022. Patients hospitalised in the ICU and outpatients were excluded.Data recordeddate, time and value of the CSC, route of administration, doses administered, sex, age, weight, haematocrit, albumin, serum creatinine and concomitant treatment.We tested the one- and two-compartmental models with four estimations: first order, first order with interaction, first order conditional and first order conditional with interaction. The influence of the recorded covariates was evaluated, selecting those that showed a statistically significant reduction in the objective function (OFV).ResultsPatients included29 patients, aged 65 years-old (28–92), 66,7% female. Mean weight was 75.1 kg (42.5–125), serum creatinine 1.12 mg/dL (0.33–4.41), serum albumin 3.5 g/dL (2.3–4.6) and haematocrit 32.6% (13.4–48.5). None of the patients received the registered drugs.The one-compartment model showed a better OFV than the two-compartment model (-663,636 vs -654,430). However, the graphical analysis showed a better correlation between the CSC and those predicted, therefore the analysis of the covariates was continued with the two-compartment model.The variables were evaluated in the two-compartment model and an influence of age and weight on clearance was observed, with statistically insignificant differences. No covariate showed an effect on the volume of distribution.Conclusion and RelevanceThe two-compartment model with first order conditional estimation with interactions showed a better goodness of fit.The development of a pharmacokinetic model of cyclosporine assists clinicians to establish an effective and safe dosing regimen.Further studies are needed to better analyse the population pharmacokinetics of cyclosporine.References and/or AcknowledgementsConflict of InterestNo conflict of interest.
Synapse-Associated Protein 97 (SAP97) is an anchoring protein that in cardiomyocytes targets to the membrane and regulates Na
and K
channels. Here we compared the electrophysiological effects of ...native (WT) and p.P888L SAP97, a common polymorphism. Currents were recorded in cardiomyocytes from mice trans-expressing human WT or p.P888L SAP97 and in Chinese hamster ovary (CHO)-transfected cells. The duration of the action potentials and the QT interval were significantly shorter in p.P888L-SAP97 than in WT-SAP97 mice. Compared to WT, p.P888L SAP97 significantly increased the charge of the Ca-independent transient outward (I
) current in cardiomyocytes and the charge crossing Kv4.3 channels in CHO cells by slowing Kv4.3 inactivation kinetics. Silencing or inhibiting Ca/calmodulin kinase II (CaMKII) abolished the p.P888L-induced Kv4.3 charge increase, which was also precluded in channels (p.S550A Kv4.3) in which the CaMKII-phosphorylation is prevented. Computational protein-protein docking predicted that p.P888L SAP97 is more likely to form a complex with CaMKII than WT. The Na
current and the current generated by Kv1.5 channels increased similarly in WT-SAP97 and p.P888L-SAP97 cardiomyocytes, while the inward rectifier current increased in WT-SAP97 but not in p.P888L-SAP97 cardiomyocytes. The p.P888L SAP97 polymorphism increases the I
, a CaMKII-dependent effect that may increase the risk of arrhythmias.
Background and Objectives
Corticosteroids are often empirically used to treat idiosyncratic hepatotoxicity with severe features. Interestingly, intravenous methylprednisolone (MP) is increasingly ...being recognized as being responsible for liver injury. We aimed to characterize MP-induced liver injury by analyzing demographical, clinical, laboratory and outcome data of three MP-induced hepatotoxicity cases and compared this information with that of previously published cases.
Case series
Three females with multiple sclerosis (MS) were treated intravenously with MP, mean daily dose 767 mg. Liver damage occurred 2 to 6 weeks after exposure. Severity was mild to moderate. Two patients suffered positive rechallenge.
Literature review
We identified 50 published cases of MP hepatotoxicity. Most of these cases were female (86%) and main treatment indications were MS (29 cases) and Graves' ophthalmopathy (13 cases). Hepatocellular damage predominated and mean time to onset was 6 weeks. Four patients died and rechallenge occurred in 19 cases.
Conclusion
MP pulses can induce severe liver injury, often with an autoimmune phenotype, particularly in patients with MS and Graves' ophthalmopathy. Consequently, these patient groups should have liver tests monitored when treated with MP to provide safer patient care.
We report for the first time the occurrence in Uruguay of three species of
Anastrepha
, which belong to the
curvicauda
species group. Specimens of
Anastrepha australis
(Blanchard, 1959),
Anastrepha ...littoralis
(Blanchard, 1959), and
Anastrepha nigra
(Blanchard, 1959) were collected with McPhail traps baited with PBX
®
yeast/borax placed in fruit orchards. These records represent the most southern distribution known for
A. littoralis
and
A. nigra
, in addition to the first host plant records for
A. nigra
, which were reared from larvae on fruits of
Araujia hortorum
E. Fourn. (Apocynaceae).
Dress induced by piperacillin-tazobactam in a child González Díaz, Carlos; González Hermosa, Andrés; García-Lirio, Eduardo ...
The journal of allergy and clinical immunology in practice (Cambridge, MA),
07/2015, Letnik:
3, Številka:
4
Journal Article
Treatment of Graves' ophthalmopathy González-García, Andrés; Sales-Sanz, Marco
Medicina clinica,
02/2021, Letnik:
156, Številka:
4
Journal Article
Recenzirano
Graves' ophthalmopathy is an inflammatory disease with primary involvement of the extraocular muscles and the orbit. It encompasses the most common extra-thyroid manifestation in patients with ...Graves-Basedow disease. The underlying cause is molecular mimicry with the TSH receptor in ocular fibroblasts, leading to an immuno-mediated pathogenesis. Glucocorticoids at high doses are the cornerstone in moderate-severe cases. However, some patients are corticorresistant or intolerant. In recent years, therapeutic novelties have been described in terms of the dosage of the immunosuppressive treatments used, as well as the emergence of biological therapy in this field. The objective of this review is to update the treatment of Graves' ophthalmopathy, as well as to present alternative options in patients resistant or intolerant to glucocorticoids.
Chronic obstructive pulmonary disease (COPD) is a major cause of illness and death among adults. In 2019, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy incorporated blood ...eosinophils as a biomarker to identify patients at increased risk of exacerbations which, with the history of exacerbations during the previous year, allows identification of patients who would benefit from anti-inflammatory treatment to reduce the risk of future exacerbations. The aim of this study was to describe demographic and clinical characteristics, eosinophil counts, and exacerbations in a cohort of COPD patients stratified by clinical phenotypes (non-exacerbator, frequent exacerbator, asthma-COPD overlap) in a Colombian cohort at 2600 meters above sea level.
A descriptive analysis of a historical cohort of patients with a confirmed diagnosis of moderate to severe COPD (FEV
/FVC < 0.7 and at least one risk factor for COPD) from two specialized centers with comprehensive disease management programs was performed from January 2015 to March 2019. Data were extracted from medical records 1 year before and after the index date.
200 patients were included (GOLD B: 156, GOLD E: 44; 2023 GOLD classification); mean age was 77.9 (SD 7.9) years; 48% were women, and 52% had biomass exposure as a COPD risk factor. The mean FEV
/FVC was 53.4% (SD 9.8), with an FEV
of 52.7% (20.7). No differences were observed between clinical phenotypes in terms of airflow limitation. The geometric mean of absolute blood eosinophils was 197.58 (SD 2.09) cells/μL (range 0 to 3,020). Mean blood eosinophil count was higher in patients with smoking history and frequent exacerbators. At least one moderate and one severe exacerbation occurred in the previous year in 44 and 8% of patients, respectively; during the follow-up year 152 exacerbations were registered, 122 (80%) moderate and 30 (20%) severe. The highest rate of exacerbations in the follow-up year occurred in the subgroup of patients with the frequent exacerbator phenotype and eosinophils ≥300 cells/μL.
In this cohort, the frequency of biomass exposure as a risk factor is considerable. High blood eosinophil count was related to smoking, and to the frequent exacerbator phenotype.
La dilatación idiopática de la aurícula derecha (DIAD) es una malformación poco frecuente caracterizada por un crecimiento desproporcionado de la aurícula derecha en ausencia de una causa estructural ...o funcional que la justifique. Presentamos el caso de una paciente con DIAD con diagnóstico desde la etapa prenatal.
La mina La Pava es parte del distrito esmeraldífero de Muzo-Quípama, Colombia; allí la presencia de esmeraldas se asocia con pelitas de la Formación Muzo. La mineralización es controlada ...espacialmente por el Anticlinal de La Pava —un pliegue por propagación de falla— y se restringe a zonas que han experimentado intensa alteración hidrotermal (albitización y carbonatización). Los principales rasgos observados en las venas productivas son las asociaciones paragenéticas de albita-xenotimo-fluorapatito y calcita-dolomita, los cuales van acompañados de anomalías geoquímicas positivas de Y, P, Mn y Mg. Adicionalmente, se presentan anomalías negativas de Li-Cs-Be-Ti que representan indicadores consistentes de la lixiviación de estos elementos en las rocas y su posterior concentración en venas y brechas hidrotermales. Se concluye que en La Pava existen parámetros estructurales, estratigráficos, mineralógicos y geoquímicos que permiten identificar bloques potenciales para hospedar mineralizaciones de esmeraldas.
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