Acute Oxcarbazepine-Induced Hepatotoxicity in a Patient Susceptible to Developing Drug-Induced Liver Injury

Oxcarbazepine (OXC) is generally accepted as a drug without risk of severe drug-induced hepatotoxicity, but according to recently reported pharmacovigilance data this statement has been challenged. However, in the literature there have been no reports of acute OXC-induced hepatotoxicity without systemic manifestations of Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome. We present a female with seizures one month after delivery who had borderline elevated liver enzymes prior to the initiation of OXC treatment. Two weeks after introducing OXC, highly elevated liver enzymes were found. After discontinuation of OXC the enzymes continued to rise for another week, and afterward gradually decreased. The causal relationship with OXC intake was determined to be highly probable. Two years later, the transitory elevation of liver enzymes was observed during the treatment of acute tonsilopharingitis with amoxicillin + clavulanic acid. The repeated elevation of liver enzymes related to use of different drugs might indicate patient`s susceptibility for drug induced liver injuries.We suggest that monitoring of liver function tests would be clinically rational for early detection of acute OXC-induced liver hepatotoxicity in the patients with clinical and/or laboratory features which might be interpreted as possible risk factors of the increased susceptibility to drug induced liver injuries

Distributed lags time series analysis versus linear correlation analysis (Pearson's r) in identifying the relationship between antipseudomonal antibiotic consumption and the susceptibility of Pseudomonas aeruginosa isolates in a single Intensive Care Unit of a tertiary hospital

The relationship between antibiotic consumption and selection of resistant strains has been studied mainly by employing conventional statistical methods. A time delay in effect must be anticipated and this has rarely been taken into account in previous studies. Therefore, distributed lags time series analysis and simple linear correlation were compared in their ability to evaluate this relationship. Data on monthly antibiotic consumption for ciprofloxacin, piperacillin/tazobactam, carbapenems and cefepime as well as Pseudomonas aeruginosa susceptibility were retrospectively collected for the period April 2006 to July 2007. Using distributed lags analysis, a significant temporal relationship was identified between ciprofloxacin, meropenem and cefepime consumption and the resistance rates of P. aeruginosa isolates to these antibiotics. This effect was lagged for ciprofloxacin and cefepime [1 month (R=0.827, P=0.039) and 2 months (R=0.962, P=0.001), respectively] and was simultaneous for meropenem (lag 0, R=0.876, P=0.002). Furthermore, a significant concomitant effect of meropenem consumption on the appearance of multidrug-resistant P. aeruginosa strains (resistant to three or more representatives of classes of antibiotics) was identified (lag 0, R=0.992, P<0.001). This effect was not delayed and it was therefore identified both by distributed lags analysis and the Pearson's correlation coefficient. Correlation coefficient analysis was not able to identify relationships between antibiotic consumption and bacterial resistance when the effect was delayed. These results indicate that the use of diverse statistical methods can yield significantly different results, thus leading to the introduction of possibly inappropriate infection control measures

Elektro fiziološki nalazi u ranom Guillain -Barréovu sindromu

The aim of the study was to identify the most common electrophysiological abnormalities in early Guillain-Barré syndrome (GBS). Neurophysiological data on 51 GBS patients assessed within 12 days of symptom onset were reviewed. Acute inflammatory demyelinating polyradiculoneuropathy (AID P) was present in 46 of 51 GBS patients. The following abnormalities were observed in our AID P patients: absent H reflex in 90.7%, conduction block in the Erb-to-axilla segment in 78.6%, motor conduction velocity suggestive of demyelination in the Erb-to-axilla segment in 45.2%, prolonged F wave latency in 65.2%-73.8% of patients but only 20.0%-37.0% with prolonged F wave latency suggestive of demyelination, and reduced or absent sensory nerve action potential in 62% of patients. Abnormal values of terminal latencies, and motor and sensory conduction velocities in distal nerve segments suggestive of demyelination were recorded in less than 30% of patients. In conclusion, the most sensitive parameter in early GBS patients is conduction block in the most proximal segments of the peripheral nervous system, directly determined in the Erbto- axilla segment or indirectly as absent H reflex. Motor conduction studies in the Erb-to-axilla segment are very informative in early GBS patients.Cilj studije bio je utvrditi najčešće elektrofiziološke nenormalnosti u ranom Guillain-Barréovu sindromu (GBS). Ispitani su neurofiziološki nalazi 51 bolesnika s GBS koji su pregledani unutar 12 dana od pojave simptoma. Akutna upalna demijelinizacijska poliradikuloneuropatija (AID P) bila je prisutna u 46 od 51 bolesnika s GBS. U bolesnika s AID P zabilježene su slijedeće nenormalnosti: odsutan H refleks u 90,7%, blokada provodljivosti u segmentu Erb do aksile u 78,5%, brzina motorne provodljivosti koja ukazuje na demijelinizaciju u segmentu Erb do aksile u 45,2%, produžena latencija F vala u 65,2%-73,8%, ali samo 20,0%-37,0% s produženom latencijom F vala koja ukazuje na demijelinizaciju, te smanjen ili odsutan akcijski potencijal senzornih živaca u 62% bolesnika. Nenormalne vrijednosti terminalnih latencija te motorne i senzorne brzine provodljivosti u distalnim segmentima živaca koje ukazuju na demijelinizaciju zabilježene su u manje od 30% bolesnika. Zaključuje se kako je blokada provodljivosti u najproksimalnijim segmentima perifernog živčanog sustava, koja se određuje izravno u segmentu Erb do aksila ili neizravno kao odsutan H refleks, najosjetljiviji parametar u bolesnika s ranim GBS. Ispitivanja motorne provodljivosti u segmentu Erb do aksila pružaju korisne informacije kod bolesnika s ranim GBS

First evidence of the presence of Multixenobiotic Resistance Mechanism activity in freshwater invasive species, signal crayfish Pacifastacus leniusculus (Dana, 1852)

Background and Purpose: The signal crayfish Pacifastacus leniusculus (Dana, 1852) is one of the most successful invasive species of crayfish in European freshwaters, an extremely diverse though endangered group of ecosystems. The main goal of this study was to functionally characterize multixenobiotic resistance (MXR) mechanism defense activity in P. leniusculus tissues for the first time. MXR mechanism protects the cell from a wide variety of toxic compounds, and it is mediated by the transport activity of ATP-binding cassette (ABC) proteins. Materials and Methods: MXR transporter activity dye assay was performed by using fluorescent model substrate rhodamine B (RB) in combination with inhibitors of MXR efflux pumps: MK571 and Verapamil, known to inhibit multidrug resistance-associated proteins (MRP) and P-glycoprotein (P-gp), respectively. In this assay, the increase in intracellular fluorescence of the substrate dye, indicates inhibition of MXR efflux protein pumps. The assay was performed in three different tissues (gills, hepatopancreas, tail muscle). Additionally, tissues were exposed to selected heavy metals – mercury (HgCl2) and zinc (ZnCl2), known to occur in open freshwaters as pollutants. Results: Optimal time for RB accumulation in gills and hepatopancreas was determined to be 30 minutes. RB efflux in gills was inhibited by MK571 and in hepatopancreas by Verapamil, suggesting that multidrug resistanceassociated proteins are dominant in gills of P. leniusculus, and P-glycoprotein in hepatopancreas. Finally, inhibitory effect of mercury (HgCl2: 10 and 20 μM) and zinc (ZnCl2: 5–20 μM) on multixenobiotic resistance mechanism activity in gills, and only mercury in hepatopancreas, was detected. Conclusions: The results for the first time demonstrate the presence of multixenobiotic resistance mechanism efflux activity as an important tissue specific defense mechanism in P. leniusculus and provide the basis for future molecular and toxicological studies of this invasive and adaptable species

The PlasmaArt Project – Application of Atmospheric-Pressure Plasma Jets in Conservation-Restoration of Wooden Objects

Projekt PlasmaArt realiziran je kao suradnja Instituta za fiziku (kao nositelja projekta) i Hrvatskog restauratorskog zavoda uz suradnju s Prehrambeno-biotehnološkim fakultetom i Biološkim odsjekom Prirodoslovnomatematičkog fakulteta. Projekt je poglavito financiran sredstvima Zaklade Adris grupe i manjim dijelom projektom IP-11 2013-2753 Hrvatske zaklade za znanost, a njime smo ispitali primjenu hladnog atmosferskog plazmenog mlaza na drvenim testnim pločicama koje vjerno simuliraju umjetnine od drva u svrhu dezinfekcije i uklanjanja stratigrafskih slojeva oslika. Iz etičkih razloga eksperimentalna ispitivanja nisu provedena na pravim umjetninama. Atmosferski plazmeni mlaz nastaje tako da se kroz staklenu kapilaru u kojoj je smještena elektroda propuhuje plin (Ar, He ili mješavina Ar i O2). Na elektrodu se narine visokofrekventni (20 kHz) visoki napon (7 kV). Atmosferski plazmeni mlazovi hladni su tip plazmi, temperature mlazova su oko 30 - 50 °C, dok je zagrijavanje tretiranog materijala puno manje (tek se nekoliko °C lokalno povisi temperatura tretiranog uzorka) pa nema nikakve termalne štete. Obrade plazmenim mlazovima Ar i He izvođene su tako da je mlaz bio usmjeren u jednu točku na površini testne pločice ili da je pločica pomicana u odnosu na mlaz. Obrada uzoraka plazmenim mlazom je beskontaktna (nema mehaničkog kontakta pa time ni mehaničkih oštećenja), a udaljenost plazmenog mlaza od uzorka može utjecati na jačinu međudjelovanja mlaza i površine, čime se može kontrolirati jačina, odnosno učinkovitost obrade. Beskontaktni hladni atmosferski plazmeni mlaz omogućio bi sigurniju obradu drvenih umjetnina kao alternativa uporabi metil-bromida, alkohola (etanol) i mehaničkog uklanjanja mikroorganizama. Ideja je da se plazmenim mlazom uklanjaju nečistoće s površina (procesima jetkanja s pomoću kisikovih radikala) i deaktiviraju mikroorganizmi, kao što su gljivice, budući da je plazmeni mlaz kemijski vrlo aktivan (MOUNIR LAROUSSI, 2002) (UV svjetlo, radikali, ozon, peroksid). Također se ispitivala mogućnost uklanjanja stratigrafskih slojeva oslika testnih pločica. Pri uklanjanju stratigrafskih slojeva udaljenost mlaza bila je 0,5 cm i s duljim djelovanjem na jednu točku na površini, za razliku od obrade dezinfekcije u kojoj je udaljenost bila 1 – 1,5 cm sa znatno kraćim vremenskim djelovanjem na jednu točku. U prvom dijelu projekta za ispitivanje uklanjanja stratigrafskih slojeva oslika izrađeno je 12 posrebrenih i 12 pozlaćenih pločica (dimenzija 3 cm x 3 cm x 2 cm). Metalizacija je izrađena samo na gornjoj stranici pločica. Testne pločice su dodatno višeslojno oslikane i/ili lakirane, s ciljem da se što vjernije imitiraju višestruki preslici, lakovi i naknadne intervencije koje se često nalaze na pravim umjetninama. Mikrouzorci slikanog sloja pločica uzeti prije i nakon obrade plazmenim mlazom poslužili su za precizniju analizu dobivenih rezultata uklanjanja stratigrafskih slojeva. Nakon probi uklanjanja stratigrafskih slojeva, može se zaključiti da plazmeni izvor nije učinkovit u tu svrhu. Naročito nije moguće uklanjati svaki sloj zasebno. Pri obradi na posrebrenim testnim pločicama primijećeno je da srebrni listić površinski oksidira pri kontaktu s plazmenim mlazom ako nema nikakav zaštitni sloj (npr. lak) na površini. Međutim, primjetna je morfološka promjena tretiranih slojeva na svim testnim pločicama. Te novonastale morfološke promjene laka nakon obrade potrebno je bolje istražiti zbog kemijskih promjena, a time se otvara mogućnost izvođenja novih istraživanja. Zaključeno je da tim tipom plazme nije moguće ukloniti stratigrafski sloj s površine, ali je primjetna morfološka promjena tretiranog sloja. U drugom dijelu projekta ispitivano je djelovanje hladnog plazmenog mlaza u svrhu dezinfekcije drvenih testnih pločica kontaminiranih gljivičnim micelijem. Prije ispitivanja utjecaja plazmenog mlaza na rast gljiva, uspostavljen je sustav uzgoja uzročnika truleži drva, i to vrsta Coniophora puteana i vrsta Serpula lacrymans na testnim pločicama. U tu svrhu izrađene su pozlaćene testne pločice od tri vrste drva (lipa, smreka, bukva), od kojih su najčešće izrađene drvene polikromirane skulpture na našem području. Utvrđeno je da gljivična vrsta C. puteana brže raste u eksperimentalnim uvjetima pa je ona korištena u ispitivanju učinkovitosti plazmenog mlaza na dezinfekciju testnih pločica. Sve tri vrste drva bile su podjednako dobar supstrat za rast gljiva, no u daljnjim pokusima korištena je lipa. Komadići krute hranjive podloge prorasli micelijem naneseni su na testne pločice i smješteni u zatvoreni sustav s visokim sadržajem vlage potrebnim za rast gljivičnih vrsta. Nakon sedam dana pri 18 °C micelij je dovoljno porastao, odnosno prekrio određeni postotak površine pozlaćenih testnih pločica. Taj postotak bio je referentni podatak u odnosu na koji se određivao daljnji rast gljiva nakon obrade. Uzorci su obrađeni različitim vrstama hladne plazme. Nakon obrade, uzorci su vraćeni u sustav na još osam dana kako bi se pratilo je li došlo do oporavka gljivice. Za proučavanje učinkovitosti dezinfekcije testnih pločica kontaminiranih gljivicama vrste C. puteana atmosferskim plazmenim mlazom načinjeno je više obrada s tri plina (helij, argon i mješavina 90 % argona i 10 % kisika) i s dvije duljine obrade (dvije minute i pet minuta). Testne pločice su pri obradi pomicane u odnosu na mlaz, kako bi se tretirala cijela gornja površina pločice na kojoj su bile izrasle gljive. Za usporedbu, testne pločice tretirane su alkoholom (96 %-tni etanol) i mehanički (standardna obrada u restauriranju/konzerviranju). Svaka obrada izvodila se na tri testne pločice da se dobiju statistički podaci za kvantizaciju učinkovitosti obrade plazmenim mlazom. Ispitivanje dezinfekcije testnih pločica dalo je pozitivne rezultate, što je bio i glavni cilj projekta. Rezultati ispitivanja pokazali su da je plazmeni mlaz Ar najučinkovitiji, budući da uvjetno nakon prve obrade nije bilo daljnjeg rasta gljivica. Također, plazmeni mlaz Ar/O2 znatno uspori napredovanje gljivica. Općenito se postiglo da obrada atmosferskim plazmenim mlazom, bez obzira na vrstu plina, daje bolje rezultate nego mehaničko uklanjanje gljivica. Uklanjanje alkoholom (96 %-tni etanol) također se pokazalo vrlo učinkovitim, odnosno potpuno je zaustavilo rast gljivica. Međutim, pri toj obradi pojavila su se i oštećenja na površini testne pločice, što je svakako negativan učinak. Iako bi bilo dobro nastaviti i proširiti ispitivanje, dobiveni rezultati upućuju na mogućnost korištenja atmosferskog hladnog plazmenog mlaza u svrhu dezinfekcije predmeta od drva. Na kraju se može zaključiti da je projekt otvorio nove mogućnosti istraživanja primjene hladnog atmosferskog plazmenog mlaza u konzerviranju-restauriranju umjetnina. Istraživanja se mogu provoditi, osim na drvu, i na drugim osjetljivim materijalima, kao što su papir i platno, što će biti tema naših budućih interdisciplinarnih istraživanja.The PlasmaArt project was realized as a collaboration between the Institute of Physics and the Croatian Conservation Institute. The project was funded mainly by the Funds of the Adris Group, and to a lesser extent by project IP-11-2013-2753 of the Croatian Science Foundation. The main idea of the project was to test the application of cold atmospheric plasma jets on wooden test plates that simulate wooden artwork for the purpose of disinfection and removal of stratigraphic layers of overpaint. For ethical reasons, experimental research was carried out not on real artwork, but on wooden test plates which had been prepared to simulate wooden artefacts. (The samples were silver-plated and gold-plated plates, painted and varnished to faithfully represent real artwork.) To test the efficiency of the disinfection effect, some of the test plates were contaminated with fungal mycelia, and to test the removal of stratigraphic layers, the rest of the silver-plated and gold-plated test plates were covered with several layers of paint and varnish. The prepared test plates were treated with cold atmospheric-pressure plasma jets. The results showed that the stratigraphic layers could not be removed, and it was not possible to remove each layer separately. As a result of the disinfection procedure, positive effects were obtained in comparison to standard procedures used in conservation, while the efficiency depended on the type of plasma and the length of the treatment. It was found that the cold atmospheric-pressure plasma jet was an effective source for disinfection of wooden artwork in the conditions described in this paper

Leitmotif: protein motif scanning 2.0

Motivation Motif-HMM (mHMM) scanning has been shown to possess unique advantages over standardly used sequence-profile search methods (e.g. HMMER, PSI-BLAST) since it is particularly well-suited to discriminate proteins with variations inside conserved motifs (e.g. family subtypes) or motifs lacking essential residues (false positives, e.g. pseudoenzymes). Results In order to make mHMM widely accessible to a broader scientific community, we developed Leitmotif, an mHMM web application with many parametrization options easily accessible through intuitive interface. Substantial improvement of performance (ROC scores) was obtained by using two novel parameters. To the best of our knowledge, Leitmotif is the only available mHMM applicatio