A5045934565- Pharmacogenetics and Drug Metabolism
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Acute Myeloid Leukemia Research
- Pharmacological Effects of Natural Compounds
- Metabolomics and Mass Spectrometry Studies
- Medical and Biological Ozone Research
- Phenothiazines and Benzothiazines Synthesis and Activities
- Hormonal and reproductive studies
- Hemoglobinopathies and Related Disorders
- Chronic Myeloid Leukemia Treatments
- Eicosanoids and Hypertension Pharmacology
- High Altitude and Hypoxia
- Tryptophan and brain disorders
- Heparin-Induced Thrombocytopenia and Thrombosis
- Clinical Laboratory Practices and Quality Control
- Renal Diseases and Glomerulopathies
- Adrenal Hormones and Disorders
- Cancer Treatment and Pharmacology
- Erythrocyte Function and Pathophysiology
- COVID-19 Clinical Research Studies
- Mast cells and histamine
- Alkaloids: synthesis and pharmacology
- Pharmacological Effects and Toxicity Studies
- Renal function and acid-base balance
- Body Composition Measurement Techniques
Azienda Ospedaliera San Gerardo
2022-2024
Istituti di Ricovero e Cura a Carattere Scientifico
2023-2024
Ospedale Valduce
2024
University of Milano-Bicocca
2022-2024
Gruppo CLAS (Italy)
1982
In polycythemia vera (PV), the prognostic relevance of an ELN-defined complete response (CR) to hydroxyurea (HU), predictors response, and patients’ triggers for switching ruxolitinib are uncertain. a real-world analysis, we evaluated their impact on clinical outcomes CR HU, correlations between partial or no (PR/NR) patient ruxolitinib. Among 563 PV patients receiving HU ≥12 months, 166 (29.5%) achieved CR, 264 PR, 133 NR. multivariate absence splenomegaly (p = 0.03), pruritus 0.002),...
The metabolism of [2'-14C]deflazacort, (11 beta, 16 beta)-21-(acetoxyl)-11-hydroxy-2'-methyl-5'H-pregna-1, 4-dieno[17,16-d]oxazole-3,20-dione, orally given to rats, dogs, and humans, has been studied. From the urine three species from rat bile liver preparations, five main metabolites I-V have isolated their structures investigated by physicochemical analysis: 1,(5 beta,11 beta,16 beta)-11,21-dihydroxy-2'-methyl-5'H-pregn-1-eno[17,16-d]oxazole-3,20-dione; II,...
Myeloproliferative neoplasms represent a heterogeneous group of acquired hematopoietic stem cell diseases in which chronic inflammation is essential for both clonal evolution and thrombotic complications. The neutrophil-to-lymphocyte ratio (NLR), reflecting the imbalance between systemic immunity, emerging as prognostic biomarker several diseases, including hematological ones.
Abstract Resistance to tyrosine kinase inhibitors (TKIs) remains a clinical challenge in Ph-positive variants of chronic myeloid leukemia. We provide mechanistic insights into previously undisclosed MEK1/2/BCR::ABL1/BCR/ABL1-driven signaling loop that may determine the efficacy arsenic trioxide (ATO) TKI-resistant leukemic patients. find activated MEK1/2 assemble pentameric complex with BCR::ABL1, BCR and ABL1 induce phosphorylation BCR::ABL1 at Tyr360 Tyr177, ABL1, Thr735 Tyr412 residues...
The kinetics and metabolic fate of 2'-14C-deflazacort, a new steroidal antiinflammatory agent, were studied in the cynomolgus monkey after both p.o. i.v. administration (5 mg/kg). There is no unchanged deflazacort plasma or urine either treatment. As judged from AUC urinary elimination values, oral availability total 14C metabolites seems to be lowered because route-dependent first-pass. Both radioactivity main metabolite (21-desacetyl deflazacort) are eliminated with half-lives 2--3-5 h....
1. The metabolic fate of a new anti-hypertensive, 1-pyrrolyl pyridazinamine, was studied in male Wistar rats after both p.o. and i.v. administration (1 mg/kg)2. compound undergoes rapid metabolism, disappearing from the central compartment with half-life about 0.5 h. Plasma concn. parent drug its major metabolite I following suggest route-dependent first-pass metabolism.3. Ten metabolites were isolated urine identified by u.v., i.r., mass 1H-n.m.r. spectroscopy. structure some confirmed...
A study of the disposition and metabolism premazepam, 3,7-dihydro-5-phenyl-6,7-dimethyl-pyrrole[3,4-e][1,4]diazepin-2-(1 H) -one, a new anti-anxiety agent, was carried out in rats dogs given 14C-labeled compound iv po. In both species, after oral administration, total radioactivity unchanged drug are rapidly absorbed peak plasma levels reached within 0.5-1 hr 2 dogs. Unchanged premazepam is cleared faster than dogs, with half-lives about 1.7 2.7 hr, respectively. Following dosage, two-thirds...
Abstract Hematological patients at higher risk of severe COVID‐19 were excluded from the acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccine trials. In this single‐center observational prospective study (NCT05074706), we evaluate immune response in hematological followed Division San Gerardo Hospital, Monza (Italy) deemed to be severely immunosuppressed after vaccination with two doses BNT162b2 vaccine. Anti‐SARS‐CoV‐2 immunoglobulin G titers above cutoff value 33.8 BAU/ml detected...
1. Disposition and metabolism of 1-methyl-3-(3-pyridyl)-5-(2-hydroxy-methylphenyl)-1H-1,2,4-triazole, a new sedative-hypnotic, were studied in rats (i.v. p.o.), cats (i.v.) human volunteers (p.o.) with 14C-labelled drug. 2. In rat man, the compound is well absorbed, extensively metabolized, excreted mostly through kidney; it has short plasma half-lives, 0.6 h rat, 0.9 1.9 cat. 3. man involves N-oxidation pyridine ring (Metabolite I), cat oxidation hydroxymethyl group II). Four other...
1. The metabolic fate of a new anti-hypertensive, 1-pyrrolyl-pyridazinamine, was studied in male Beagle dogs given both p.o. and i.v. doses the 14C-labelled drug (1 mg/kg).2. compound as single injection disappeared from central compartment wirh half-life about 0.9h. Plasma levels total 14C were represented mostly by metabolites.3. Eight urinary metabolites designated I, II XI-XVI purified their structures assigned means u.v., i.r., n.m.r. mass spectrometry.4. Quantitatively primary attack...
The metabolic pathways of the non-hormonal anti-fertility agent 3-(2-ethylphenyl)-5-(3-methoxyphenyl)-1H-1,2,4-triazole (DL 111-IT) were studied in rats given 14C-labelled compound intramuscularly. diaryltriazole, once absorbed, was metabolized rapidly by three phase I reactions: (a) hydroxylation at C-4 methoxyphenyl ring, (b) alpha-C ethyl chain, and (c) demethylation methoxyl function. Seven free metabolites conjugates have been isolated characterized u.v., i.r., n.m.r. mass spectroscopy....
The metabolism of zetidoline, a new neuroleptic, in the rat and dog has been studied. From urine rats dogs given 5 mg/kg [2-14C] zetidoline orally, unchanged drug five metabolites were isolated structures four them assigned by physicochemical analysis. They are: metabolite B, 4'-hydroxy-3'-chlorophenyl zetidoline; D, without aryl group; E, 6'-hydroxy-4'-beta-D-glucuronide F, 4'-beta-D-glucuronide B. plasma levels its after iv administration show that is rapidly excreted and/or metabolized...
Topic: 4. Acute myeloid leukemia - Clinical Background: “myelodysplasia-related” and “post-cytotoxic therapies”, as defined by 2022 WHO classification, previously named AML-MRC therapy-related AML, represent very high-risk subgroups of AML with adverse biological features. CPX-351, a liposomal formulation cytarabine/daunorubicin, represents relevant innovation in the treatment this subtype: significant increase OS without toxicity excess, compared to SOC, was reported phase 3 study Lancet et...
Topic: 16. Myeloproliferative neoplasms - Clinical Background: (MPNs) are characterized by dysregulation in JAK-STAT pathway that determine the clonal expansion of one or more blood cell lineages. In addition to these intracellular changes malignant clone, inflammatory processes involving both and non-clonal cells contribute signs symptoms patients (pts), as well progression disease myelofibrosis (MF) acute leukemia, thrombotic complications. Neutrophil-to-lymphocyte ratio (NLR) reflects...