Data on positive rechallenge in idiosyncratic drug-induced liver injury (DILI) are scarce. We aim to analyse the clinical presentation, outcome and drugs associated with positive rechallenge in two ...DILI registries.
Cases from the Spanish and Latin American DILI registries were included. Demographics, clinical characteristics and outcome of cases with positive rechallenge according to CIOMS/RUCAM and current definitions were analysed.
Of 1418 patients with idiosyncratic DILI, 58 cases had positive rechallenge (4.1%). Patients with positive rechallenge had shorter duration of therapy (p=0.001) and latency (p=0.003). In patients with rechallenge, aspartate transaminase levels were increased (p=0.026) and showed a prolonged time to recovery (p=0.020), albeit no differences were seen in terms of fatal outcomes. The main drug implicated in rechallenge was amoxicillin-clavulanate (17%). The majority of re-exposure events were unintentional (71%). Using both existing definitions of positive rechallenge, there were four cases which exclusively fulfilled the current criteria and five which only meet the historical definition. All cases of positive rechallenge, irrespective of the pattern of damage, fulfilled the criteria of either alanine transaminase (ALT) ≥3 times the upper limit of normal (ULN) and/or alkaline phosphatase (ALP) ≥2 times ULN.
Episodes of rechallenge were characterised by shorter duration of therapy and latency, and longer time to resolution, but did not show an increased incidence of fatal outcome. Based on our findings, ALT ≥3 times ULN and/or ALP ≥2 times ULN, regardless of the pattern of damage, is proposed as a new definition of rechallenge in DILI.
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•Data on positive rechallenge in idiosyncratic drug-induced liver injury are scarce.•Positive rechallenge is characterised by shorter treatment duration and latency.•Poor outcome rates did no differ between first and rechallenged DILI episodes.•Evidence-based definition of rechallenge is proposed ALT≥3 ULN and/or ALP≥2 ULN.
Preventing recurrences and metastasis of prostate cancer after prostatectomy by administering adjuvant therapies is quite a controversial issue. In addition to effectiveness, absence of side effects ...and long term toxicity are mandatory. Curcuminoids (Curc) extracted with innovative techniques and effectively loaded by polymeric nanobubbles (Curc-NBs) satisfy such requirements. Curc-NBs showed stable over 30 d, were effectively internalized by tumor cells and were able to slowly release Curc in a sustained way. Significant biological effects were detected in PC-3 and DU-145 cell lines where Curc-NBs were able to inhibit adhesion and migration, to promote cell apoptosis and to affect cell viability and colony-forming capacity in a dose-dependent manner. Since the favourable effects are already detectable at very low doses, which can be reached at a clinical level, the actual drug concentration can be visualized and monitored by US or MRI, Curc-NBs can be proposed as an effective adjuvant theranostic tool.
Summary
Background
We have observed an increase in hepatotoxicity (DILI) reporting related to the use of anabolic androgenic steroids (AAS) for bodybuilding.
Aim
To characterise phenotype ...presentation, outcome and severity of AAS DILI.
Methods
Data on 25 cases of AAS DILI reported to the Spanish (20) and Latin‐American (5) DILI Registries were collated and compared with previously published cases.
Results
AAS DILI increased from representing less than 1% of the total cases in the Spanish DILI Registry in the period 2001–2009 to 8% in 2010–2013. Young men (mean age 32 years), requiring hospitalisation, hepatocellular injury and jaundice were predominating features among the AAS cases. AAS DILI caused significantly higher bilirubin values independent of type of damage when compared to other drug classes (P = 0.001). Furthermore, the cholestatic AAS cases presented significantly higher mean peak bilirubin (P = 0.029) and serum creatinine values (P = 0.0002), compared to the hepatocellular cases. In a logistic regression model, the interaction between peak bilirubin values and cholestatic damage was associated with the development of AAS‐induced acute kidney impairment (AKI) OR 1.26 (95% CI: 1.035–1.526); P = 0.021, with 21.5 ×ULN being the best bilirubin cut‐off point for predicting AKI risk (AUCROC 0.92). No fatalities occurred.
Conclusions
Illicit recreational AAS use is a growing cause of reported DILI that can lead to severe hepatic and renal injury. AAS DILI is associated with a distinct phenotype, characterised by considerable bilirubin elevations independent of type of damage. Although hepatocellular injury predominates, acute kidney injury develops in cholestatic cases with pronounced jaundice.
Objective: Nanoparticle-based imaging and nanocarriers therapies have emerged as essential tools for many fields of modern medicine, in order to track the fate of cells and optimize drug delivery. Up ...to now, however, there are only few reports on the effect of nanocarriers of different types on oxygen delivery, even though this would be of great interest for the design of high impact therapies in several cardiovascular diseases (CVDs). In particular. Cyclodextrin Nanosponges (C-NS) can be envisioned as innovative tools to improve the delivery of oxygen in a controlled manner in CVDs. Methods: We tested oxygenated C-NS (OX-C-NS) at different concentrations (0.2. 2 and 20 μg/ml) for their capability to reduce cell mortality during hypoxia and reoxygenation (H/R) protocols. For comparative purpose, we also tested "blank materials" (C-NS filled with nitrogen gas without oxygen) and the effects of C-NS in Normoxia. To test the effectiveness of C-NS. we used H9c2. a cardiomyoblast cell line derived from rat heart, exposed to Normoxia (5% C02 and 21% 02) or Hypoxia (5% C02 and 95%N2) in a Hypoxic Chamber. The cellular mortality was measured with MTT assay. Results: In Normoxia. regardless of OX-C-NS formulation, the H9c2 cells displayed a tendency to an increased proliferation, which seemed somewhat correlated to the concentration of OX-C-NS used. The different concentration of OX-C-NS. applied before Hypoxia. induced a significant reduction of cell mortality compared to C-NS without oxygen. Also, the application of OX-C-NS at the beginning of reoxygenation induced a marked reduction of cell death. Conclusions: OX-C-NS may induce H9c2 cell proliferation in Normoxia and may protect H9c2 from H/R injury in vitro. The administration of oxygen in a controlled manner during or after an ischemic event may be an innovative approach for reduction of Ischemia/Reperfusion injury, with consequent reduction of chronic CVDs. Our preliminary results, and in particular the observation of a remarkable efficacy in reoxygenation. suggest an interesting potentiality for medical application of C-NS during the treatment of myocardial infarction. Further studies are required to ascertain the protective potential of C-NS on cardiac l/R injury under in vivo conditions.
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