M. Cabello

Role of chemical structures and the 1331T>C bile salt export pump polymorphism in idiosyncratic drug-induced liver injury

Several pharmaceutical compounds have been shown to exert inhibitory effects on the bile salt export pump (BSEP) encoded by the ABCB11 gene. We analysed the combined effect on drug‐induced liver injury (DILI) development of the ABCB11 1331T>C polymorphism and the presence of specific chemical moieties, with known BSEP inhibiting properties, in the causative drug.

Spatial and temporal variation of the impact of an extreme Saharan dust event

[1]xa0The impact on PM10, meteorology and visibility of the severe Saharan dust outbreak registered in Europe in October 2008 is evaluated in detail in mainland Spain and the Balearic Islands. Data from a large number of air quality stations (261), METAR observations at 39 airports, besides records from meteorological networks, were used. Information from dispersion models, satellite observations, synoptic charts and back-trajectory analysis, supported the interpretation. During the event, 89% of the monitoring stations exceeded the daily limit value. The highest daily averaged PM10 concentration across Spain ranged from 378 to 18μg m−3, following a hyperbolic decay with increasing latitude. An opposite relationship between visibility and PM10 was found for data at 12 UTC. The strength of the episode may be related to strong subsidence at low levels over the Iberian Peninsula.

Aminoglycoside-associated nephrotoxicity in extrahepatic obstructive jaundice

Experimental data demonstrate that biliary obstruction increases renal sensitivity to gentamicin. In the present study the incidence of and risk factors for aminoglycoside nephrotoxicity were prospectively studied in patients with extrahepatic obstructive jaundice. Two hundred and thirty-seven hospitalized adult patients were classified into three groups. Group I consisted of 84 patients with extrahepatic obstructive jaundice, who received aminoglycoside (gentamicin or tobramycin). Group II consisted of 81 patients with extrahepatic obstructive jaundice, who received either antibiotics other than aminoglycoside or no antimicrobial therapy. Group III consisted of 72 noncholestatic patients receiving aminoglycosides for different disorders. Nephrotoxicity developed in 27 patients (32%) in group I vs 9 patients (11%) in group II and 4 patients (5.6%) in group III (p < 0.00001). In group I, a comparison of patients with and without nephrotoxicity revealed significantly higher values in the former for mean serum bilirubin concentration, initial steady-state trough aminoglycoside concentration and estimated half-life. Stepwise multivariate analysis with nephrotoxicity status as the dependent variable determined that the most significant variable for predicting nephrotoxicity was serum total bilirubin level. In extrahepatic cholestasis a high serum bilirubin level is a distinct factor predisposing to aminoglycoside nephrotoxicity.

Case Report: Acute Liver Failure After Treatment with Nefazodone

Nefazodone , a new serotonine rgic modulating antidepressant drug approved for treatment of major depression acts by blocking the postsynaptic 5-HT2A receptor and inhibiting serotonin and noradre naline uptake . Its side -effect pro® le demonstrates that it has decreased anticholine rgic, antihistam inic, a -adrenolytic, and sedative activity relative to traditional antidepressants (1). Although such agents (2, 3) have been associated with a low incide nce of idiosyncratic hepatic injury, we report a patient with acute live r failure associated with nefazodone .

Herbal and Dietary Supplement-Induced Liver Injuries in the Spanish DILI Registry

Background & Aims There have been increasing reports of liver injury associated with use of herbal and dietary supplements, likely due to easy access to these products and beliefs among consumers that they are safer or more effective than conventional medications. We aimed to evaluate clinical features and outcomes of patients with herbal and dietary supplement‐induced liver injuries included in the Spanish DILI Registry. Methods We collected and analyzed data on demographic and clinical features, along with biochemical parameters, of 32 patients with herbal and dietary supplement‐associated liver injury reported to the Spanish DILI registry from 1994 through 2016. We used analysis of variance to compare these data with those from cases of liver injury induced by conventional drugs or anabolic androgenic steroid‐containing products. Results Herbal and dietary supplements were responsible for 4% (32 cases) of the 856 DILI cases in the registry; 20 cases of DILI (2%) were caused by anabolic androgenic steroids. Patients with herbal and dietary supplement‐induced liver injury were a mean age of 48 years and 63% were female; they presented a mean level of alanine aminotransferase 37‐fold the upper limit of normal, 28% had hypersensitivity features, and 78% had jaundice. Herbal and dietary supplement‐induced liver injury progressed to acute liver failure in 6% of patients, compared with none of the cases of anabolic androgenic steroid‐induced injury and 4% of cases of conventional drugs. Liver injury after repeat exposure to the same product that caused the first DILI episode occurred in 9% of patients with herbal and dietary supplement‐induced liver injury vs none of the patients with anabolic androgenic steroid‐induced injury and 6% of patients with liver injury from conventional drugs. Conclusion In an analysis of cases of herbal and dietary supplement‐induced liver injury in Spain, we found cases to be more frequent among young women than older patients or men, and to associate with hepatocellular injury and high levels of transaminases. Herbal and dietary supplement‐induced liver injury is more severe than other types of DILI and re‐exposure is more likely. Increasing awareness of the hepatoxic effects of herbal and dietary supplements could help physicians make earlier diagnoses and reduce the risk of serious liver damage.

Study of the cosmogenic factors influence on temporal variation of 7Be air concentration during the 23rd solar cycle in Málaga (South Spain)

Atmospheric 7Be activity concentrations were measured in Málaga (South Spain) during the period 1997–2007. Monthly concentrations of 7Be ranged between 2.47 and 8.12xa0mBqxa0m−3 showing seasonal trend with maxima in spring–summer time. Influence of solar activity, cosmic rays and aerosol optical depth on airborne 7Be was analyzed. Weak negative correlation between sunspot number and 7Be is found. Instead, both solar energetic protons >100xa0MeV and cosmic rays show positive weak significant correlation with this radionuclide. Meteorology may contribute to the low correlation coefficients found. Aerosol optical depth exhibits significant correlation with 7Be, confirming that this radionuclide attaches to atmospheric particles.

Factors controlling temporal variability of gamma radionuclides and major-ions of bulk deposition in Málaga

AbstractnConcentrations of both gamma radionuclides as well as major ions in bulk deposition samples were measured monthly from January 2005–December 2013 and January 2007–December 2013 respectively. The gamma radionuclides present are 7Be, 210Pb and 40K (50xa0% of the samples), while ions in bulk deposition were dominated by Ca2+, Cl−,

Imipenem/cilastatin-associated hiccups.

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