<abstract xml:lang="en"><title style='display:none'>Suicide by Fentanyl</title>Fentanyl is a potent, short-acting narcotic analgesic widely used as surgical anaesthetic. This article presents a case in which fentanyl was self-injected by a 41-year old nurse, an employee at the hospital emergency department, who was found dead at home. She had no known history of drug and alcohol abuse. Two syringes, one empty and one filled with a clear liquid, were found near the body, while a needle was stuck into her hand.Toxicological analysis showed fentanyl poisoning. Fentanyl overdose was declared the cause of death and the manner of death was classified as suicide.To our knowledge, death due to the intravenous injection of fentanyl has not previously been reported in Croatia.</abstract>

Suicide by Fentanyl

National Poison Control Centre, Medical Faculty, Military Medical Academy, University of Defence, Belgrade, Serbia

Department of Toxicology “Akademik Danilo Soldatović”, Faculty of Pharmacy, University of Belgrade, Belgrade, 11000 Belgrade, Serbia

Department of Toxicology “Akademik Danilo Soldatović”, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia

Fresh Frozen Plasma as a Successful Antidotal Supplement in Acute Organophosphate Poisoning

<abstract xml:lang="en"><title style='display:none'>Dioxins and Human Toxicity</title>The term dioxins usually refers to polychlorinated dibenzo-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs). As 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD) has the highest toxic potential, the toxic potentials of other PCDDs and PCDFs are defined in comparison with it. Human exposure to dioxins can be environmental (background), occupational, or accidental pollution. In the human body, dioxins are in part metabolised and eliminated, and the rest is stored in body fat. People vary in their capacity to eliminate TCDD, but it is also dose-dependent; the elimination rate is much faster at higher than lower levels. The liver microsomal P4501A1 enzyme oxygenates lipophilic chemicals such as dioxins. It is encoded by the CYP1A1 gene. Cytosolic aryl hydrocarbon receptor (AhR) mediates their carcinogenic action. It binds to dioxin, translocates to nucleus and together with hydrocarbon nuclear translocator (ARNT) and xenobiotic responsive element (XRE) increases the expression of CYP1A1.Dioxins are classified as known human carcinogens, but they also cause noncancerous effects like atherosclerosis, hypertension, and diabetes. Long-term exposures to dioxins cause disruption of the nervous, immune, reproductive, and endocrine system. Short-term exposure to high levels impairs the liver function and causes chloracne. The most sensitive population to dioxin exposure are the foetuses and infants.A large number of health effects have been documented in the scientific literature, and they all place dioxins among the most toxic chemicals known to man.</abstract>

Department of Chemistry and Biochemistry, Zagreb University School of Medicine

Medikol Outpatient Clinic, Zagreb, Croatia

Forensic Science Centre "Ivan Vučetić", General Police Directorate, Ministry of Interior, Zagreb, Croatia

Dioxins and Human Toxicity

<abstract xml:lang="en"><title style='display:none'>Contaminants of Medicinal Herbs and Herbal Products</title>Medicinal plants have a long history of use in therapy throughout the world and still make an important part of traditional medicine. Thus, medicinal plants and herbal products must be safe for the patient (consumer). This review addresses biological contaminants (microbes and other organisms) and chemical contaminants (mycotoxins, toxic elements such as heavy metals, and pesticide residues) as major common contaminants of medicinal herbs and herbal products. To prevent and screen for contamination and ensure safety and conformity to quality standards, medicinal herbs and herbal products should be included in appropriate regulatory framework.</abstract>

Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia

Agency for Medicinal Products and Medical Devices, Zagreb, Croatia

Contaminants of Medicinal Herbs and Herbal Products

<abstract xml:lang="en"><title style='display:none'>T-2 Toxin: Incidence and Toxicity in Poultry</title>T-2 toxin is the most toxic type A trichothecene mycotoxin. It is the secondary metabolite of the Fusarium fungi, and is common in grain and animal feed. Toxic effects have been shown both in experimental animals and in livestock. It has been implicated in several outbreaks of human mycotoxicoses. Toxic effects in poultry include inhibition of protein, DNA, and RNA synthesis, cytotoxicity, immunomodulation, cell lesions in the digestive tract, organs and skin, neural disturbances and low performance in poultry production (decreased weight gain, egg production, and hatchability). Concentrations of T-2 toxin in feed are usually low, and its immunosuppressive effects and secondary infections often make diagnosis difficult. If at the onset of the disease, a change in diet leads to health and performance improvements in animals, this may point to mycotoxin poisoning. Regular control of grain and feed samples is a valuable preventive measure, and it is accurate only if representative samples are tested. This article reviews the incidence and toxic effects of T-2 toxin in poultry.</abstract>

Poultry Centre of the Croatian Veterinary Institute, Zagreb, Croatia

Institute for Medical Research and Occupational Health, Zagreb, Croatia

T-2 Toxin: Incidence and Toxicity in Poultry

<abstract xml:lang="en"><title style='display:none'>Mechanisms of Organophosphate Toxicity and Detoxication with Emphasis on Studies in Croatia</title>This review comprises studies on the mechanisms of toxicity and detoxication of organophosphorus (OP) compounds done in Croatia in different research areas. One area is the synthesis of antidotes against OP poisoning and their <italic>in vivo</italic> testing in experimental animals. <italic>In vitro</italic> studies included in this review focus on the mechanisms of reversible inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), protection of cholinesterases from inhibition by OPs, and reactivation of phosphylated cholinesterases. The third area comprises distribution profiles of BChE and paraoxonase (PON) phenotypes in selected population groups and the detection of OPs and metabolites in humans. Finally, methods are described for the detection of OP compounds in human blood and other media by means of cholinesterase inhibition.</abstract>

Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, La Jolla, CA, USA

Mechanisms of Organophosphate Toxicity and Detoxication with Emphasis on Studies in Croatia

<trans-abstract xml:lang="hr">
<title style='display:none'>Abstract</title>
Liječenje olanzapinom može dovesti do prolaznih abnormalnosti u jetrenim biokemijskim nalazima i takva se lijekom prouzročena oštećenja jetre obično nadziru mjerenjem razina alanin aminotransferaze (ALT) i aspartat aminotransferaze (AST) u krvi, a alfa-glutation-S-transferaza (α-GST) ne mjeri se rutinski u klinici premda može poslužiti kao raniji i specifičniji biomarker oštećenja jetre. Osjetljivost jetre na lijekove može dosta ovisiti o polimorfizmu gena regulatora aktivnosti enzima uključenih u procese detoksifikacije i popravka DNA. Cilj je ovoga istraživanja bio ocijeniti koji je od triju jetrenih enzima – α-GST, ALT i AST – najosjetljiviji biomarker olanzapinom prouzročenog oštećenja jetre te kako polimorfizmi gena <italic>GSTT1</italic>, <italic>GSTM1</italic>, <italic>GSTP1</italic> i <italic>OGG1</italic> utječu na njihove razine u 30 bolesnika koji su primali taj lijek. Suprotno našoj hipotezi, povišenje serumskih razina α-GST-a nije bilo značajno više od povišenja razina transaminaza. ALT se pokazao ranijim biomarkerom oštećenja jetre od ostalih dvaju enzima. Osim toga, nismo otkrili značajnu povezanost između genskih polimorfizama i razina enzima, izuzev za povezanost genotipa <italic>GSTP1 Ile/Val + Val/Val</italic> s ALT-om, što upozorava na povećani rizik od lijekom prouzročenog oštećenja jetre u nositelja ovoga genotipa. Buduća bi istraživanja mogla pomoći u prepoznavanju mehanizama uslijed kojih dolazi do prolaznog povišenja razina ovog jetrenog enzima povezanoga s ovim genotipom.
</trans-abstract>

Are changes in olanzapine-induced liver enzyme levels associated with <italic>GSTT1</italic>, <italic>GSTM1</italic>, <italic>GSTP1</italic>, and <italic>OGG1</italic> gene polymorphisms?

<trans-abstract xml:lang="hr">
<title style='display:none'>Abstract</title>
Trovanje organofosfornim spojevima kritično je stanje koje rano može dovesti do depresije središnjeg živčanog sustava, zatajenja disanja i smrti. Budući da je prema kliničkoj slici blisko srodno trovanju karbamatnim pesticidima, cilj je ovoga članka prikazati slučaj pogrešne dijagnoze, koja je isprva trovanje karbofuranom identificirala kao trovanje organofosfatom u bolesnika u kojega se sumnjalo na toplinski udar. Usporedno dajemo slučaj namjernog samotrovanja organofosfatom diklorvosom da bismo naglasili koliko je velika vjerojatnost trovanja pesticidima u bolesnika s akutnim kolinergičnim simptomima kod kojih se ne zna progutana tvar. U takvim se slučajevima može započeti empirijsko liječenje atropinom i oksimom dok se ne ustanovi pravovremena diferencijalna dijagnoza i po potrebi prilagodi liječenje.
</trans-abstract>

Comparative analysis of organophosphorus versus carbamate pesticide poisoning: a case study

<trans-abstract xml:lang="hr">
<title style='display:none'>Abstract</title>
Izloženost ljudi česticama plastike izaziva veliku zabrinutost svih značajnih sudionika koji su uključeni u zaštitu ljudskoga zdravlja zbog onečišćenja prehrambenog lanca, površinskih voda, čak i pitke vode, kao i zbog njihove postojanosti i bioakumulacije. Stoga je ključno bolje razumijevanje biološke sudbine plastike i njezine interakcije s različitim biološkim sustavima. Zbog učestalosti materijala plastike u okolišu i njihove potencijalne toksičnosti, važno je prikupiti pouzdane, regulatorno značajne i znanstveno utemeljene podatke o učincima mikro- i nanoplastike na ljudsko zdravlje kako bi se pravilno primijenile pouzdane strategije procjene rizika i upravljanja rizicima u kružnoj ekonomiji lanca vrijednosti plastike. Ovaj pregledni rad predstavlja trenutačno znanje o dozama izloženosti mikro- i nanoplastici relevantnima za ljude, oblicima izloženosti, kao i o njezinim toksičnim učincima. Istaknute su poteškoće u pravilnoj procjeni problema izloženosti plastici i trenutačni nedostatci u znanju te su predloženi potencijalni koraci koji se mogu poduzeti kako bi se podržala percepcija, procjena i ublažavanje rizika za zdravlje strogim znanstveno utemeljenim dokazima. Na temelju postojećih znanstvenih podataka o štetnim učincima mikro- i nanoplastike na zdravlje, daju se preporuke za razvoj specifičnih načina nepoželjnih ishoda (eng. <italic>adverse outcome pathway</italic>, krat. AOP) za mikro- i nanoplastiku prema priručniku korisnika AOP-a Organizacije za ekonomsku suradnju i razvoj (izv. Organisation for Economic Co-operation and Development, krat. OECD).
</trans-abstract>

Science-based evidence on pathways and effects of human exposure to micro- and nanoplastics

<trans-abstract xml:lang="hr">
<title style='display:none'>Abstract</title>
Direktne metode detekcije dopinga u sportu neprestano se suočavaju s novim supstancijama, kratkim vremenskim okvirima i granicama mogućnosti detekcije, stoga su indirektne metode detekcije neizbježan dio suvremene borbe protiv dopinga. Referentne vrijednosti na razini populacije i univerzalne granice kao indirektne metode pokazale su nedostatnost, a multidisciplinarna istraživanja dovela su do implementacije Atletske biološke putovnice (ABP) s hematološkim i steroidnim modulom. Atletska biološka putovnica je longitudinalni profil mjerenih hematoloških i biokemijskih biomarkera – zajedno s izračunanim rezultatima, a u usporedbi s epidemiološkim podatcima koji su ključni za otkrivanje dopinga. U obama modulima ABP-a parametri se analiziraju Bayesovim adaptivnim modelom, što dovodi do personaliziranih referentnih i graničnih vrijednosti, a to poboljšava njegovu osjetljivost. Zbunjujući čimbenici s dokazanim i potencijalnim utjecajem na biomarkere (npr. etničko podrijetlo, izloženost nadmorskoj visini) također su važni u analizi ABP-a. Bez sumnje, ABP je promijenio borbu protiv dopinga. Razvijanje novih modula (npr. endokrinološki), novih parametara (npr. neovisnih o volumenu plazme) i dopuna neizravnih metoda (npr. transkriptomika) mogu dodatno povećati važnost ABP-a u budućnosti.
</trans-abstract>

Athlete biological passport: longitudinal biomarkers and statistics in the fight against doping

<trans-abstract xml:lang="hr">
<title style='display:none'>Abstract</title>
Na temelju rezultata Europske zdravstvene ankete, cilj ovoga rada bio je utvrditi udio osoba starijih od 18 godina u Republici Hrvatskoj koje hodaju 210 i više minuta tjedno te istražiti povezanost redovitoga hodanja sa sociodemografskim čimbenicima, zdravstvenim ponašanjima i kroničnim nezaraznim bolestima/stanjima. Pomoću EHIS-PAQ upitnika prikupljeni su podatci o količini hodanja odraslih osoba tijekom uobičajenog tjedna u minutama. Podatci su dodatno analizirani prema spolu, dobi, obrazovanju, urbanizaciji, županijama i regijama, (ne)pušenju, drugim oblicima tjelesne aktivnosti te prema bolestima/kroničnim stanjima. Rezultati su pokazali kako ukupno 40,9 % odrasle populacije hoda 210 ili više minuta tjedno. Najveći udjeli populacije koja hoda 210 i više minuta tjedno zabilježeni su u Ličko-senjskoj županiji (76,8 %), među onima koji provode 300 i više minuta tjedno u zdravstveno usmjerenoj aerobnoj tjelesnoj aktivnosti izvan posla (57,6 %), onima koji su izvijestili da imaju šećernu bolest (49,3 %) te onima koji imaju između 65 i 74 godine (44,7 %). Unatoč svojim ograničenjima, naše istraživanje pruža vrijedan uvid u učestalost i čimbenike koji određuju zdrave šetačke navike na reprezentativnom uzorku odraslih Hrvata te pruža temelj za daljnja istraživanja.
</trans-abstract>

Frequency of regular walking among Croatian adults

<trans-abstract xml:lang="hr">
<title style='display:none'>Abstract</title>
Zdravstveni radnici koji rukuju antineoplastičnim lijekovima u posebnim jedinicama za njihovu pripremu izlažu se zagađenim površinama i riziku od s njima povezanim mutagenim, teratogenim i onkogenim učincima. Da bi se smanjio taj rizik, u posljednjih se 20-ak godina ručna priprema intravenskih lijekova sve više zamjenjuje automatiziranom. Da bismo ocijenili rizik od zagađenja i kakvoću radnog okoliša zdravstvenih radnika koji pripremaju antineoplastične lijekove, oslonili smo se na metodu analize mogućih pogrešaka u postupcima i kritičnosti njihovih posljedica (engl. <italic>failure mode effects and criticality analysis</italic>, krat. FMECA) radi usporedbe prihvatljive razine rizika (engl. <italic>acceptable risk level</italic>, krat. ARL), koja je zbroj ocjena prioriteta rizika (eng. <italic>risk priority number</italic>, krat. RPN) pet utvrđenih načina pogreške s izmjerenom razinom rizika (engl. <italic>measured risk level,</italic> krat. MRL). Taj nam je model pokazao da antineoplastični lijekovi u prahu i spremnicima koji nisu zaštićeni vanjskim plastičnim omotačem donose povećani rizik, ali nismo utvrdili dosljednu razliku u riziku od zagađenja između ručne i automatizirane pripreme. Ovaj pristup može biti koristan u procjeni i kontroli rizika od profesionalne izloženosti u zdravstvenih radnika rezidualnim citotoksičnim spojevima, bilo da se radi o postojećim ili tek planiranim/novoosmišljenim postupcima pripreme lijekova. Podatci dobiveni redovitim nadzorom (monitoringom) istodobno mogu poslužiti za praćenje kakvoće radnih uvjeta tako što će se usporediti s predviđenim profilom rizika koji je utvrđen ARL-om. Iako je naše istraživanje pokazalo da automatizirana priprema ima prednost nad ručnom u smislu sigurnosti, prostora za njezino poboljšanje ima podosta, naročito u našim četirima bolnicama koje su sudjelovale u istraživanju.
</trans-abstract>

Evaluation of the risk of occupational exposure to antineoplastic drugs in healthcare sector: part II – the application of the FMECA method to compare manual vs automated preparation

<abstract xml:lang="en"><title style='display:none'>Surfactants in the Environment</title>Surfactants are a diverse group of chemicals that are best known for their wide use in detergents and other cleaning products. After use, residual surfactants are discharged into sewage systems or directly into surface waters, and most of them end up dispersed in different environmental compartments such as soil, water or sediment. The toxic effects of surfactants on various aquatic organisms are well known. In general, surfactants are present in the environment at levels below toxicity and in Croatia below the national limit. Most surfactants are readily biodegradable and their amount is greatly reduced with secondary treatment in wastewater treatment plants. The highest concern is the release of untreated wastewater or wastewater that has undergone primary treatment alone. The discharge of wastewater polluted with massive quantities of surfactants could have serious effects on the ecosystem. Future studies of surfactant toxicities and biodegradation are necessary to withdraw highly toxic and non-biodegradable compounds from commercial use and replace them with more environmentally friendly ones.</abstract>

Surfactants in the Environment

<abstract xml:lang="en"><title style='display:none'>Thallium Toxicity in Humans</title>Thallium is a naturally occurring trace element, widely distributed in the earth's crust, but at very low concentrations. It does not have a known biological use and does not appear to be an essential element for life. It has been considered one of the most toxic heavy metals.Occasionally, there are reports on thallium poisoning as results of suicide or murder attempt or accident. The main threat to humans is through occupational exposure, environmental contamination, and accumulation in food, mainly in vegetables grown on contaminated soil. Increasing use in emerging new technologies and demanding high-tech industry constantly raise concern about exposure risk to all living organisms. Thallium is considered a cumulative poison that can cause adverse health effects and degenerative changes in many organs. The effects are the most severe in the nervous system. The exact mechanism of thallium toxicity still remains unknown, although impaired glutathione metabolism, oxidative stress, and disruption of potassium-regulated homeostasis may play a role. The lack of data about mutagenic, carcinogenic, or teratogenic effects of thallium compounds in humans calls for further research.</abstract>

Department of Molecular Biology, Faculty of Science, University of Zagreb, Zagreb, Croatia

University Hospital Merkur, Medical School, University of Zagreb, Zagreb, Croatia

Thallium Toxicity in Humans

<abstract xml:lang="en"><title style='display:none'>Toxicological Properties of Citrinin</title>Citrinin (CTN) is a nephrotoxic mycotoxin produced by several fungal strains belonging to the genera <italic>Penicillium, Aspergillus</italic>, and <italic>Monascus.</italic> It contaminates various commodities of plant origin, cereals in particular, and is usually found together with another nephrotoxic mycotoxin, ochratoxin A (OTA). These two mycotoxins are believed to be involved in the aetiology of endemic nephropathy. In addition to nephrotoxicity, CTN is also embryocidal and fetotoxic. The genotoxic properties of CTN have been demonstrated with the micronuleus test (MN), but not with single-cell gel electrophoresis. The mechanism of CTN toxicity is not fully understood, especially not whether CTN toxicity and genotoxicity are the consequence of oxidative stress or of increased permeability of mitochondrial membranes. CTN requires complex cellular biotransformation to exert mutagenicity.Compared with other mycotoxins, CTN contamination of food and feed is rather scarce. However, it is reasonable to believe that humans are much more frequently exposed to CTN than generally accepted, because it is produced by the same moulds as OTA, which is a common contaminant of human food all over the world.At present, there are no specific regulations either in Croatia or in the European Union concerning CTN in any kind of commodity.</abstract>

Toxicological Properties of Citrinin

<abstract xml:lang="en"><title style='display:none'>Cadmium Toxicity Revisited: Focus on Oxidative Stress Induction and Interactions with Zinc and Magnesium</title>Discovered in late 1817, cadmium is currently one of the most important occupational and environmental pollutants. It is associated with renal, neurological, skeletal and other toxic effects, including reproductive toxicity, genotoxicity, and carcinogenicity. There is still much to find out about its mechanisms of action, biomarkers of critical effects, and ways to reduce health risks. At present, there is no clinically efficient agent to treat cadmium poisoning due to predominantly intracellular location of cadmium ions. This article gives a brief review of cadmium-induced oxidative stress and its interactions with essential elements zinc and magnesium as relevant mechanisms of cadmium toxicity. It draws on available literature data and our own results, which indicate that dietary supplementation of either essential element has beneficial effect under condition of cadmium exposure. We have also tackled the reasons why magnesium addition prevails over zinc and discussed the protective role of magnesium during cadmium exposure. These findings could help to solve the problem of prophylaxis and therapy of increased cadmium body burden.</abstract>

Cadmium Toxicity Revisited: Focus on Oxidative Stress Induction and Interactions with Zinc and Magnesium

<abstract xml:lang="en"><title style='display:none'>Genetic Polymorphism of Metabolic Enzymes P450 (CYP) as a Susceptibility Factor for Drug Response, Toxicity, and Cancer Risk</title>The polymorphic P450 (CYP) enzyme superfamily is the most important system involved in the biotransformation of many endogenous and exogenous substances including drugs, toxins, and carcinogens. Genotyping for <italic>CYP</italic> polymorphisms provides important genetic information that help to understand the effects of xenobiotics on human body. For drug metabolism, the most important polymorphisms are those of the genes coding for CYP2C9, CYP2C19, CYP2D6, and CYP3A4/5, which can result in therapeutic failure or severe adverse reactions. Genes coding for CYP1A1, CYP1A2, CYP1B1, and CYP2E1 are among the most responsible for the biotransformation of chemicals, especially for the metabolic activation of pre-carcinogens. There is evidence of association between gene polymorphism and cancer susceptibility. Pathways of carcinogen metabolism are complex, and are mediated by activities of multiple genes, while single genes have a limited impact on cancer risk. Multigenic approach in addition to environmental determinants in large sample studies is crucial for a reliable evaluation of any moderate gene effect. This article brings a review of current knowledge on the relations between the polymorphisms of some CYPs and drug activity/toxicity and cancer risk.</abstract>

Clinical Institute of Laboratory Diagnosis, Zagreb University School of Medicine and University Hospital Centre Zagreb, Zagreb, Croatia

Department of Pharmacology, Zagreb University School of Medicine, Zagreb, Croatia

Genetic Polymorphism of Metabolic Enzymes P450 (CYP) as a Susceptibility Factor for Drug Response, Toxicity, and Cancer Risk

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