Chemical Methods for Determination of Hydroxylated Metabolites of Polycyclic Aromatic Hydrocarbons and Polychlorinated Biphenyls in Biological Material

U ovome preglednom radu prikazani su postupci analize hidroksiliranih metabolita policikličkih aromatskih ugljikovodika i poliklorbifenila u ljudima i životinjama. Ti metaboliti služe kao biomarkeri izloženosti ljudi i životinja navedenim zagađivalima, no neki od njih i sami posjeduju toksična svojstva. Analiziraju se najčešće u urinu koji je kao uzorak najdostupniji, ali se isto tako mogu analizirati i u ljudskoj, odnosno životinjskoj jetri, žuči i masnom tkivu. Analiza metabolita aromatskih zagađivala važna je zbog određivanja biodostupnosti aromatskih zagađivala, njihove potencijalne toksičnosti u ljudskom organizmu, ali i zbog toksičnosti samih metabolita. Napredak analitičkih metoda omogućio je simultanu analizu velikog broja metabolita u uzorcima. Nove tehnike ekstrakcije i selektivnije i preciznije kvalitativne i kvantitativne analize omogućuju detekciju vrlo niskih koncentracija metabolita. Pri tome dodatnu prednost imaju jednostavne tehnike koje zahtijevaju manje kemikalija i vremena za analizu.This review presents methods for the analysis of hydroxylated metabolites of polycyclic aromatic hydrocarbons and polychlorinated biphenyls in humans and animals. These metabolites serve as biomarkers of human and animal exposure to the mentioned pollutants, but some metabolites also have toxic properties. Most are analysed in urine, which is the most accessible sample, but they can also be analysed in human and animal liver, bile, and adipose tissue. Their analysis is important for assessing bioavailability of aromatic pollutants and their toxicity in human organism, but also the toxicity of metabolites themselves. Advancements in analytical methods have made it possible to analyse multiple metabolites in a sample at the same time. New extraction techniques and more precise and selective qualitative and quantitative analyses can now detect very low metabolite oncentrations. An extra advantage is that these simple techniques require less chemicals and time

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes

A proposal for a CT driven classification of left colon acute diverticulitis

Computed tomography (CT) imaging is the most appropriate diagnostic tool to confirm suspected left colonic diverticulitis. However, the utility of CT imaging goes beyond accurate diagnosis of diverticulitis; the grade of severity on CT imaging may drive treatment planning of patients presenting with acute diverticulitis. The appropriate management of left colon acute diverticulitis remains still debated because of the vast spectrum of clinical presentations and different approaches to treatment proposed. The authors present a new simple classification system based on both CT scan results driving decisions making management of acute diverticulitis that may be universally accepted for day to day practice

Levels and Distribution of PCBs and Organochlorine Pesticides in the Air, Pine Needles, and Human Milk

U ovome preglednom radu prikazani su rezultati dobiveni diljem svijeta o raspodjeli i razinama 20 kongenera poliklorbifenila (PCB) i 7 organoklorovih pesticida (OCP) u uzorcima zraka, majčina mlijeka i borovih iglica. Istraživanja prisutnosti navedenih spojeva u tim uzorcima dugi niz godina provode se i u Institutu za medicinska istraživanja i medicinu rada te su u ovome preglednom radu sažeti i ti rezultati. Vidljivo je da su se koncentracije organoklorovih spojeva značajno snizile nakon zakonske zabrane njihove upotrebe, no to se snižavanje usporilo i oni se još nalaze u svim uzorcima. Općenito, više razine PCB-a nađene su u uzorcima s urbanog područja, razine pesticida više u onima gdje je vjerojatno u prošlosti postojala njihova primjena u poljoprivredi, dok je razina HCB-a obično pokazatelj industrijske aktivnosti. γ-HCH određen je u najvišoj koncentraciji u uzorcima zraka i borovih iglica, dok su u ljudima najzastupljeniji DDE i β-HCH. Indikatorski kongeneri PCB-a također su različito zastupljeni u okolišu i ljudima te su tako u zraku i borovim iglicama više koncentracije hlapljivijih nižekloriranih PCB-a, a u ljudima postojanijih višekloriranih PCB-a. Od toksičnih ortho-supstituiranih kongenera PCB-a i u uzorcima ljudi i okoliša najzastupljeniji je PCB-118, dok su najrjeđe detektirana tri najtoksičnija ne-ortho-supstituirana kongenera: PCB-77, PCB-126 i PCB-169. Od organoklorovih pesticida DDD u svim je uzorcima određen u najnižim koncentracijama.This review presents the findings on the distribution and levels of 20 congeners of polychlorinated biphenyls (PCBs) and 7 organochlorine pesticides (OCPs) all over the world, based on measurements in samples of air, human milk and pine needles. The Institute for Medical Research and Occupational Health has been conducting research in all three matrices for many years, and this review summarises its results too. Significant decrease in concentrations of organochlorine compounds has been seen after the legal ban of their use, but that decresing trend has been slowed down and they are still found in all samples. In general, higher PCB levels are found in samples from urban locations, pesticides levels are higher in samples from locations where has been their probable usage in agriculture, while HCB levels are usually indicator of industrial activity. γ-HCH has been found in the highest concentration in air and pine needles samples, while in humans DDE and β-HCH are the most abundant compounds. Indicator PCB congeners are also differently present in environment and humans: in air and pine needles lower-chlorinated, more volatile PCB congeners have higher concentrations while in humans that goes for more persistent higher-chlorinated PCB congeners. Among toxic ortho-substituted PCB congeners in human and environmental samples the most abundant is PCB-118 while three non-ortho substituted congeners (PCB-77, PCB-126 and PCB-169) that are the most toxic ones are rarely detected. From organochlorine pesticides, DDD is found in lowest concentrations in all samples