[Translated article] Pharmaceutical recommendations for therapeutic appropriateness in patients with multiple sclerosis.

OBJECTIVE: To determine the prevalence of PIMDINAC criteria and to implement pharmacological interventions in a population with multiple sclerosis over 55 years of age. METHODS: Retrospective, observational, open-label study, including patients with multiple sclerosis aged 55 years and older during December 2022 and February 2023. The main variable determined was the percentage of compliance with the PIMDINAC criteria. RESULTS: Ninety-five patients were included, with the presence of PIMDINAC criteria detected in 67.4%. The most frequently detected criterion was non-adherence to concomitant treatment (84.4%), followed by drug-drug interactions (56.2%) and potentially inappropriate medication (25%). A total of 20 pharmaceutical interventions were performed in 17 patients (17.9%). Potentially inappropriate medication was responsible for 11 interventions, non-adherence for 7, and drug-drug interactions for 2. The 81.8% of interventions were accepted, resulting in the discontinuation of 15 inappropriately prescribed drugs. The prevalence of PIMDINAC criteria in this group of patients is high. The study revealed that PIMDINAC criteria were prevalent in 67.4% of the study population, with polypharmacy playing an important role, suggesting the potential for a multidisciplinary approach, through pharmaceutical interventions to address unnecessary or duplicate treatments.

Pharmaceutical recommendations for therapeutic appropriateness in multiple sclerosis patients. / Recomendaciones farmacéuticas de adecuación terapéutica en pacientes con esclerosis múltiple.

OBJECTIVE: To determine the prevalence of PIMDINAC criteria and to implement pharmacological interventions in a population with multiple sclerosis over 55 years of age. METHODS: Retrospective observational open-label study including patients with multiple sclerosis aged 55 years and older between December 2022 and February 2023. The main variable determined was the percentage of compliance with the PIMDINAC criteria. RESULTS: Ninety-five patients were included, with the presence of PIMDINAC criteria detected in 67.4%. The most frequently detected criterion was non-adherence to concomitant treatment (84,4%), followed by drug-drug interactions (56.2%) and potentially inappropriate medication (25%). A total of 20 pharmaceutical interventions were performed in 17 patients (17.9%). Potentially inappropriate medication was responsible for 11 interventions, non-adherence for 7 and drug-drug interactions for 2. The 81.8% of interventions were accepted, resulting in the discontinuation of 15 inappropriately prescribed drugs. The prevalence of PIMDINAC criteria in this group of patients is high. The study revealed that PIMDINAC criteria were prevalent in 67.4% of the study population, with polypharmacy playing an important role, suggesting the potential for a multidisciplinary approach, through pharmaceutical interventions to address unnecessary or duplicate treatments.

A Real-World Evidence-Based Study of Long-Term Tyrosine Kinase Inhibitors Dose Reduction or Discontinuation in Patients with Chronic Myeloid Leukaemia.

The therapeutic approach to chronic myeloid leukaemia (CML) has changed in recent years. As a result, a high percentage of current patients in the chronic phase of the disease almost have an average life expectancy. Treatment also aims to achieve a stable deep molecular response (DMR) that might allow dose reduction or even treatment discontinuation. These strategies are often used in authentic practices to reduce adverse events, yet their impact on treatment-free remission (TFR) is a controversial debate. In some studies, it has been observed that as many as half of patients can achieve TFR after the discontinuation of TKI treatment. If TFR was more widespread and globally achievable, the perspective on toxicity could be changed. We retrospectively analysed 80 CML patients treated with tyrosine kinase inhibitor (TKI) at a tertiary hospital between 2002 and 2022. From them, 71 patients were treated with low doses of TKI, and 25 were eventually discontinued, 9 of them being discontinued without a previous dose reduction. Regarding patients treated with low doses, only 11 of them had molecular recurrence (15.4%), and the average molecular recurrence free survival (MRFS) was 24.6 months. The MRFS outcome was not affected by any of the variables examined, including gender, Sokal risk scores, prior treatment with interferon or hydroxycarbamide, age at the time of CML diagnosis, the initiation of low-dose therapy and the mean duration of TKI therapy. After TKI discontinuation, all but four patients maintained MMR, with a median follow-up of 29.2 months. In our study, TFR was estimated at 38.9 months (95% CI 4.1-73.9). This study indicates that low-dose treatment and/or TKI discontinuation is a salient, safe alternative to be considered for patients who may suffer adverse events (AEs), which hinder the adherence of TKI and/or deteriorate their life quality. Together with the published literature, it shows that it appears safe to administer reduced doses to patients with CML in the chronic phase. The discontinuation of TKI therapy once a DMR has been reached is one of the goals for these patients. The patient should be assessed globally, and the most appropriate strategy for management should be considered. Future studies are needed to ensure that this approach is included in clinical practice because of the benefits for certain patients and the increased efficiency for the healthcare system.

Clinical outcomes after CPX-351 in patients with high-risk acute myeloid leukemia: A comparison with a matched cohort from the Spanish PETHEMA registry.

BACKGROUND: CPX-351 is approved for the treatment of therapy related acute myeloid leukemia (t-AML) and AML with myelodysplastic related changes (MRC-AML). The benefits of this treatment over standard chemotherapy has not been addressed in well matched cohorts of real-life patients. METHODS: Retrospective analysis of AML patients treated with CPX-351 as per routine practice. A propensity score matching (PSM) was used to compare their main outcomes with those observed in a matched cohort among 765 historical patients receiving intensive chemotherapy (IC), all of them reported to the PETHEMA epidemiologic registry. RESULTS: Median age of 79 patients treated with CPX-351 was 67 years old (interquartile range 62-71), 53 were MRC-AML. The complete remission (CR) rate or CR without recovery (CRi) after 1 or 2 cycles of CPX-351 was 52%, 60-days mortality 18%, measurable residual disease <0.1% in 54% (12 out of 22) of them. Stem cell transplant (SCT) was performed in 27 patients (34%), median OS was 10.3 months, and 3-year relapse incidence was 50%. Using PSM, we obtained two comparable cohorts treated with CPX-351 (n = 52) or IC (n = 99), without significant differences in CR/CRi (60% vs. 54%) and median OS (10.3 months vs. 9.1 months), although more patients were bridged to SCT in the CPX-351 group (35% vs. 12%). The results were confirmed when only 3 + 7 patients were included in the historical cohort. In multivariable analyses, SCT was associated with better OS (HR 0.33 95% CI: 0.18-0.59), p < 0.001. CONCLUSION: Larger post-authorization studies may provide evidence of the clinical benefits of CPX-351 for AML in the real-life setting.

Metagenomes of a Crystallizer Pond from Isla Cristina Saltern in Spain.

The metagenomic sequences of the prokaryotic microbiota from the brine of a crystallizer pond with 42% (wt/vol) salinity of a saltern located in Isla Cristina, Huelva, southwest Spain, were obtained by Illumina. Haloarchaea and members of the bacterial genus Salinibacter were the most abundant prokaryotes.

Genomic-based phylogenetic and metabolic analyses of the genus Natronomonas, and description of Natronomonas aquatica sp. nov.

The genus Natronomonas is classified on the family Haloarculaceae, within the class Halobacteria and currently includes six species isolated from salterns, saline or soda lakes, and salt mines. All are extremely halophilic (optimal growth at 20-25% [w/v] NaCl) and neutrophilic, except Natronomonas pharaonis, the type species of the genus, that is haloalkaliphilic (showing optimal growth at pH 9.0) and possesses distinct phenotypic features, such as a different polar lipid profile than the rest of species of the genus. We have carried out a genome-based study in order to determine the phylogenetic structure of the genus Natronomonas and elucidate its current taxonomic status. Overall genomic relatedness indexes, i.e., OrthoANI (Average Nucleotide Identity), dDDH (digital DNA-DNA hybridization), and AAI (Average Amino acid Identity), were determined with respect to the species of Natronomonas and other representative taxa of the class Halobacteria. Our data show that the six species of Natronomonas constitute a coherent cluster at the genus level. Besides, we have characterized a new haloarchaeon, strain F2-12T, isolated from the brine of a pond of a saltern in Isla Cristina, Huelva, Spain, and we determined that it constitutes a new species of Natronomonas, for which we propose the name Natronomonas aquatica sp. nov. Besides, the metabolic analysis revealed a heterotrophic lifestyle and a versatile nitrogen metabolism for members of this genus. Finally, metagenomic fragment recruitments from a subset of hypersaline habitats, indicated that the species of Natronomonas are widely distributed in saline lakes and salterns as well as on saline soils. Species of this haloarchaeal genus can be considered as ubiquitous in intermediate to high salinity habitats.

Incidence and management of patients with methotrexate delayed elimination in the clinical practice: A Delphi study.

INTRODUCTION: High-dose methotrexate (HDMTX) is administered for the treatment of some cancers. HDMTX is usually safe but may crystallize in renal tubules causing acute kidney injury (AKI). Consequently, MTX elimination is delayed, resulting in a severe and life-threatening condition. No studies have been published about the impact of MTX toxicity in Spain. This study aims to estimate the incidence and management of MTX delayed elimination and toxicity. METHODS: A two-round Delphi study was performed to reach consensus between 10 medical experts on haemato-oncology and paediatric oncology with experience in the management of HDMTX treated patients from leading Spanish hospitals. An online questionnaire was developed based on national and international guidelines and previous evidence regarding HDMTX-related toxicity. Consensus was established at 80% agreement. Median and interquartile ranges were calculated, and incidence data were extrapolated to the Spanish general population. RESULTS: Out of 1.475 patients estimated to receive HDMTX treatment annually in Spain, 27.5% present MTX delayed elimination and 11.6% develop HDMTX-induced AKI (35.4% with severe systemic toxicities (>grade 3) and 18.8% develop chronic renal disease). Mortality is estimated in 4.2%. Immuno-enzymatic assay is used in most of the hospitals (90%) for MTX serum level monitoring. All experts use increased supportive care and high leucovorin as first-line treatment. Available treatments in experts' hospitals in case toxicity persists are haemodialysis (90% of hospitals), glucarpidase (60%) and hemofiltration (50%). Most prevalent non-renal systemic toxicities are haematologic and mucositis (21-40% of patients). Patients with HDMTX-induced AKI require from intensive care (5% of patients), more than 3 sessions and 4 days of dialysis, and about 8.5 days of hospitalization (non-ICU patients) and 12 days in case of patients requiring ICU. CONCLUSIONS: These results are the first evidence regarding HDMTX-induced AKI in Spain. Incidence and mortality results are in line with previous studies. Clinical management is based on preventive measures and the treatment depend on the availability in the hospital. The need for effective, safe and rapid treatment for the reduction of MTX toxic levels and the improvement of monitoring methods were noted by experts as urgent needs. Further observational studies to validate these results would be needed.

Treatment of Chronic Lymphocytic Leukemia in the Personalized Medicine Era.

Chronic lymphocytic leukemia is a lymphoproliferative disorder marked by the expansion of monoclonal, mature CD5+CD23+ B cells in peripheral blood, secondary lymphoid tissues, and bone marrow. The disease exhibits significant heterogeneity, with numerous somatic genetic alterations identified in the neoplastic clone, notably mutated TP53 and immunoglobulin heavy chain mutational statuses. Recent studies emphasize the pivotal roles of genetics and patient fragility in treatment decisions. This complexity underscores the need for a personalized approach, tailoring interventions to individual genetic profiles for heightened efficacy. The era of personalized treatment in CLL signifies a transformative shift, holding the potential for improved outcomes in the conquest of this intricate hematologic disorder. This review plays a role in elucidating the evolving CLL treatment landscape, encompassing all reported genetic factors. Through a comprehensive historical analysis, it provides insights into the evolution of CLL management. Beyond its retrospective nature, this review could be a valuable resource for clinicians, researchers, and stakeholders, offering a window into the latest advancements. In essence, it serves as a dynamic exploration of our current position and the promising prospects on the horizon.

Impact of Genetic Polymorphisms and Biomarkers on the Effectiveness and Toxicity of Treatment of Chronic Myeloid Leukemia and Acute Myeloid Leukemia.

Most malignant hematological diseases are generally a consequence of acquired mutations or rearrangements in cell replication processes. Acute myeloid leukemia (AML) is a clinically and molecularly heterogeneous disease that results from acquired genetic and epigenetic alterations in hematopoietic progenitor cells. Despite the advances made in understanding the pathogenesis of this disease, the overall survival of patients remains very low due to the high relapse rate. Pharmacogenetics and massive sequencing studies have allowed the identification of new recurrent mutations with significant prognostic impact in AML; furthermore, it seems likely that whole genome sequencing will soon become a standard diagnostic test, which will allow the molecular diagnosis of patients. Therefore, it is necessary to develop molecular targets that open new therapeutic perspectives and allow individualized treatment of patients with this aggressive disease. Chronic myeloid leukemia (CML) is the first neoplastic disease for which a characteristic genetic alteration was described. It has, by definition, a genetic marker, the BCR::ABL1 rearrangement, as a consequence of the t9;22(q34;q11) translocation. Its study is essential for the diagnosis of this entity and also for monitoring the response to treatment. Drugs known as tyrosine kinase inhibitors (TKIs) that target the BCR::ABL1 protein (oral targeted therapy) are the conventional treatment of CML, representing a change of paradigm in the management of oncohematological patients.

Amiloidosis muscular. A propósito de un caso clínico / Muscle amyloidosis. About a clinical case / Amiloidose muscular. Sobre um caso clínico

Resumen: La amiloidosis engloba distintas enfermedades caracterizadas por el depósito extracelular de una proteína anómala e insoluble (amiloide) en los diferentes tejidos, causando su disfunción progresiva. La presentación clínica suele ser heterogénea, lo que determina el diagnóstico tardío. Para alcanzarlo se requiere de biopsia del tejido afectado, la demostración del depósito amiloide y la tipificación de la proteína que lo constituye. La detección precoz permite optimizar el tratamiento, condicionando esto el pronóstico. La miopatía amiloide asociada a una discrasia de células plasmáticas es una causa infrecuente de hipertrofia muscular; por lo que en el siguiente artículo se busca presentar un caso clínico de la misma con posterior revisión de la literatura.

Abstract: Amyloidosis encompasses various diseases characterized by the extracellular deposition of an abnormal and insoluble (amyloid) protein among the different tissues, causing its progressive dysfunction. The clinical presentation is usually heterogeneous, which determines the delays in diagnosis. To achieve this, a biopsy of the affected tissue, the demonstration of amyloid deposit and the typing of the protein that constitutes it are required. Early detection allows optimizing the treatment, conditioning the prognosis. Amyloid myopathy associated with plasma cell dyscrasia is an infrequent cause of muscle hypertrophy, for which reason the following article seeks to present a clinical case of it with a subsequent review of the literature.

Resumo: A amiloidose engloba diferentes doenças caracterizadas pela deposição extracelular de uma proteína anormal e insolúvel (amiloide) em diferentes tecidos, causando sua disfunção progressiva. A apresentação clínica costuma ser heterogênea, o que determina o diagnóstico tardio. Para tanto, é necessária a biópsia do tecido afetado, a demonstração do depósito amilóide e a tipagem da proteína que o constitui. A detecção precoce permite otimizar o tratamento, condicionando o prognóstico. A miopatia amilóide associada à discrasia das células plasmáticas é uma causa rara de hipertrofia muscular; Portanto, o seguinte artigo busca apresentar um caso clínico desta com posterior revisão da literatura.

SEGHI Study: Defining the Best Surveillance Strategy in Hodgkin Lymphoma after First-Line Treatment.

The optimal strategy for early surveillance after first complete response is unclear in Hodgkin lymphoma. Thus, we compared the various follow-up strategies in a multicenter study. All the included patients had a negative positron emission tomography/computed tomography at the end of induction therapy. From January 2007 to January 2018, we recruited 640 patients from 15 centers in Spain. Comparing the groups in which serial imaging were performed, the clinical/analytical follow-up group was exposed to significantly fewer imaging tests and less radiation. With a median follow-up of 127 months, progression-free survival at 60 months of the entire series was 88% and the overall survival was 97%. No significant differences in survival or progression-free survival were found among the various surveillance strategies. This study suggests that follow-up approaches with imaging in Hodgkin lymphoma provide no benefits for patient survival, and we believe that clinical/analytical surveillance for this group of patients could be the best course of action.

Tailored Langmuir-Schaefer Deposition of Few-Layer MoS2 Nanosheet Films for Electronic Applications.

Few-layer MoS2 films stay at the forefront of current research of two-dimensional materials. At present, continuous MoS2 films are prepared by chemical vapor deposition (CVD) techniques. Herein, we present a cost-effective fabrication of the large-area spatially uniform films of few-layer MoS2 flakes using a modified Langmuir-Schaefer technique. The compression of the liquid-phase exfoliated MoS2 flakes on the water subphase was used to form a continuous layer, which was subsequently transferred onto a submerged substrate by removing the subphase. After vacuum annealing, the electrical sheet resistance dropped to a level of 10 kΩ/sq, being highly competitive with that of CVD-deposited MoS2 nanosheet films. In addition, a consistent fabrication protocol of the large-area conductive MoS2 films was established. The morphology and electrical properties predetermine these films to advanced detecting, sensing, and catalytic applications. A large number of experimental techniques were used to characterize the exfoliated few-layer MoS2 flakes and to elucidate the formation of the few-layer MoS2 Langmuir film.

An elevated concentration of MoS2 lowers the efficacy of liquid-phase exfoliation and triggers the production of MoOx nanoparticles.

It is generally accepted that liquid-phase exfoliation (LPE) enables large-scale production of few-layer MoS2 flakes. In our work, we studied in detail few-layer MoS2 oxidation in the course of standard LPE in a water/ethanol solution. We demonstrate that an increase of the initial MoS2 concentration above a certain threshold triggers a pronounced oxidation and the exfoliation process starts to produce MoOx nanoparticles. A subsequent decrease of the water pH along with an increased content of SO42- suggests an oxidation scenario of few-layer MoS2 oxidation towards MoOx nanoparticles. Moreover, the lowered pH leads to agglomeration and sedimentation of the few-layer MoS2 flakes, which significantly lowers their production yield. We employed a large number of physico-chemical techniques to study the MoS2-to-MoOx transformation and found a threshold value of 10 mg ml-1 of the initial MoS2 concentration to trigger this transformation.

Development of dried serum spot sampling techniques for the assessment of trace elements in serum samples by LA-ICP-MS.

A novel approach for serum analysis by dried matrix spot (DMS) technique is proposed. The methodology consists of sampling filter paper discs (2.7 mm in diameter) containing the large amount of serum retained after a single spotting. Several oxidizers (sodium chlorate, sodium azide, acetic acid, formic acid, 1-butyl-3-methylimidazoliumm chloride/bromide) were tested (oxidizers premixed with the sample before spotting, and papers previously soaked in concentrated additive/oxidizer solutions). Direct multi-element determination (Al, Be, Ca, Cu, Fe, K, Li, Mg, Mn, Mo, Na, P, Rb, Se, V, and Zn) in dried serum spots at very low levels was therefore assessed by laser ablation (LA) coupled with inductively coupled plasma - mass spectrometry (ICP-MS). Laser ablation was performed using a focused Nd: YAG laser beam in lineal scan mode (wavelength 213 nm, laser fluency 2.2 J cm-2, repetition rate 20 Hz, laser spot diameter 90 µm, depth 0 µm, scanning speed 12 µm s-1). Matrix-matched calibration mode and 13C as internal standard (for signal intensities normalization) was used throughout the work. Limits of quantification were found to be from 21 µg L-1 to 221 mg L-1. Repeatability (seven ablations of the same dried serum spot) and reproducibility (two ablations of seven dried serum spot from the same material) offered RSDs below 12% for all analytes, which seems satisfactory for clinical purposes. The method was validated by analyzing several certified reference materials (Seronorm™ level I and II trace elements in serum), and it was applied to several DMS from serum samples from healthy adults.

Plume Dynamics of Laser-Produced Swine Muscle Tissue Plasma.

We report on the plume dynamics of the plasma induced by laser ablation of a swine skeletal muscle tissue sample in different vacuum conditions. Pulses from a transversely excited atmospheric CO2 laser were focused onto a target sample and the induced plasma was allowed to expand in different air pressures. The expansion features were studied using fast photography of the overall visible emission by using a gated intensified charged coupled device. Free expansion and plume splitting were observed at different pressure levels. The expansion of the plasma plume front was analyzed using various expansion models and the velocity of the plume front was estimated. The effect of the number of accumulated laser shots on the crater volume at different ambient air pressures and an elemental analysis of the sample were performed using scanning electron microscopy coupled with energy dispersive X-ray spectroscopy (EDX) analysis. The surface morphology of the irradiated surface showed that increasing the pressure of the ambient gas decreased the ablated mass, or in other words it reduced significantly the laser-target coupling.

HPLC-ICPMS and stable isotope-labeled approaches to assess quantitatively Ti(IV) uptake by transferrin in human blood serum.

Little is known about the effects of titanium found in patients wearing prostheses or about the biochemical pathways of this metal when used as an anticancer drug (e.g., titanocene dichloride). In this work, transferrin has been confirmed as the only carrier protein binding Ti in human blood serum samples by making use of different HPLC protein separations followed by element-specific Ti detection by ICPMS. Besides, isotope dilution analysis has been applied to the quantitative speciation of Ti-Tf in standards and human blood serum samples. Species-unspecific and species-specific isotope dilution modes have been explored. In the first case, very low Ti-Tf results were obtained even using two different chromatographic mechanisms, anion exchange (20-24%) and size exclusion (33-36%). Surprisingly, no major Ti species except Ti-Tf were observed in the chromatograms, suggesting that Ti(IV) hydrolysis and precipitation as inactive titanium oxide species could take place inside the chromatographic columns. These results demonstrate that chemical degradation of metalloproteins during analytical separations could ruin the sought speciation quantitative results. The isotope dilution species-specific mode, much more accurate in such cases, has been instrumental in demonstrating the possibility of gross errors in final metalloprotein quantification. For this purpose, an isotopically enriched standard of (49)Ti-Tf was synthesized and applied to the quantitative speciation of Ti-Tf again. Using this species-specific spike, Ti-Tf dissociation inside the chromatographic columns used could be corrected, and thus, quantitative Ti-Tf binding in serum (92-102%) was observed. In other words, the usefulness and potential of a species-specific isotope dilution analysis approach to investigate quantitatively metal-protein associations, which can be dissociated at certain experimental conditions, is demonstrated here for the first time.

Insulin-like growth factor-1 receptor regulation in activated human T lymphocytes.

OBJECTIVE: To investigate the kinetics of insulin-like growth factor-1 receptor (IGF-1R) expression in PHA-stimulated T lymphocytes. METHODS: IGF-1R protein and mRNA were detected by flow cytometry and RT-PCR respectively, between 0 and 48 h after cell activation. RESULTS: Few minutes after T lymphocytes were activated, internalization of the IGF-1R from the cell membrane was observed, achieving the lower level between 1 and 6 h and was accompanied by a reduction in its mRNA. This was followed by re-expression of IGF-1R on the cell surface and an increase in IGF-1R mRNA levels in the cytoplasm, reaching levels higher than those recorded initially after 48 h activation. CONCLUSION: This down- and up-regulation suggests that restoration of IGF-1R would be the result of receptor recycling and de novo synthesis and highlights its importance for T lymphocyte proliferation.

Glucocorticoid regulation of in vitro astrocyte phagocytosis

Astrocytes participate in central nervous system injury, degenerative diseases and also perform macrophagic functions. The present work investigates: 1) the effect of the physiological glucocorticoid corticosterone (CORT) and the synthetic agonist dexamethasone (DEX) on latex beads phagocytosis by neonatal rat cortical astrocytes in culture, and 2) the expression of immunoreactive glucocorticoid receptors (GR) in astrocytes cultured in different media with or without a pulse application of CORT. The results indicated that glucocorticoids reduced astrocyte phagocytic activity, as occurred with macrophages, independently of the culturing conditions employed. The extent of phagocytosis was inversely related to nuclear immunostaining for GR in cultures in fetal calf serum, which contained endogenous glucocorticoid. However, no correlation was found between nuclear GR and phagocytosis for cultures in glucocorticoid-free medium or in medium containing CORT. It is suggested that additional factors, besides the GR, may be involved in glucocorticoid modulation of astrocyte phagocytosis.

Effect of 11 beta OH pregna-1,4-diene-3,20-dione (deltaHOP) on thymocyte plasma membranes

En trabajos anteriores se demostró que la acción inibitoria del esteroide delta HOP a altas concentraciones no era consecuencia de un efecto genómico como en el caso de los glucocorticoides. Para investigar si este efecto se producía a traves de la membrana plasmática, en este trabajo se estudió , en tromocitos de ratas, las alteraciones producidas por estos esteroides en la fuidez de la membrana por polarización de fluorescencia con 1,6-difenil-1, 3, 5-hexatrieno (DPH) y la movilidad de las proteínas de susperficie por la formación de "caps" con concanavalina A fluorescente (Con A-fl). La polarización de fluorescencia disminuyó con los glucocorticoides por aumento de la fluidez de la membrana, mientras que la alfa HOP no produjo ningún cambio. En los experimentos con Con A-fl se observó una disminución del inúmero de células con "cap" cuando se incubó con delta HOP y con los inhibidores de "caps" (citocalasina B y acida sódica), mientras que los glucocorticoides no tuvieron efecto inhibidor. El tratamiento "in vitro" con delta HOP o glucocorticoides produjo el mismo efecto que "in vitro". Estos resultados sugieren que la delta HOP actúa en forma superficial sobre la membrana plasmática, in hibiendo la movilidad de las proteínas de superficie, pero no alterando la fluidez de la bicapa lipídica

Appearance and persistence of 113-hydroxypregnant-1, 4-diene-3, 20-dione (delta HOP) effect in vivo

Se estudió el efecto "in vitro" de la 11ß-hidroxipregna-1,4-diene-3,20 diona (DeltaHOP) en ratones tratados en forma aguda y crónica con el esteroide, en conparación con los tratados con dexametasona y vehículo. En los experimentos agudos, una inyección de DeltaHOP de 2 mg/100 gm de peso animal tuvo su máximo efecto inhibitorio en la incorporación de uridina-H3 por los timocitos después de 18 h, desapareciendo el efecto a las 36 h, no observándose cambios en los niveles de corticosterona plasmática. Una dosis de 0.033 mg/100 gm de peso animal de dexametasona produjo inhibición en la incorporación de uridina 5 h después de la inyección, juntamente con una disminución significativa de los niveles de corticosterona plasmática; este efecto desapereció a las 12 h, mientras que el ejercido sobre el timo recién desapareció a las 24 h. En el tratamiento crónico DeltaHOP produjo la máxima inhibición 5 h después de la última inyección y se mantuvo hasta las 36 h sin modificar la corticosterona plasmática. En cambio la dexametasona produjo la misma inhibición que DeltaHOP, pero el efecto desapareció antes ( a las 18 h); en estos animales la corticosterona se mantuvo baja hasta las 18 h. En tratamientos crónicos, después de 5 h de la última inyección, DeltaHOP no modificó los pesos de timos y bazos, pero éstos disminuyeron significativamente con el tratamiento de dexametasona. Estos resultados sugieren que la acción "in vivo" de DeltaHOP es diferente a la de los glucocorticoides