63. Raki Płaskonabłonkowe głowy i szyi u młodych dorosłych – retrospektywna wieloczynnikowa analiza oraz wstępne wyniki badań nad rolą czynnika genetycznego w ich etiopatogenezie

Celem pracy jest analiza cech klinicznych raków płaskonabłonkowych głowy i szyi u chorych poniżej 45 roku życia („young adult”) oraz ocena udziału czynnika genetycznego w ich etiopatogenezie. W ocenie klinicznej uwzględniono dane dotyczące: A.- pacjentów: wiek (średnia 40.9 lat), płeć (mężczyźni 85%, kobiety 15%) oraz ekspozycja na typowe czynniki ryzyka (palący papierosy −96.8%, spożywający alkohol −96.7%), B.- guza: lokalizacja (krtań 69%, jama ustna i gardło 28%), stopień zaawansowania klinicznego (głównie stadium IV −58.7%), typ histologiczny (ca planoepitheliale keratodes 71.2%, akeratodes 28.8%) i stopień zróżnicowania histologicznego (głownie G1+G2 −94.3%), C.- zastosowanego leczenia: metoda (głównie skojarzone: operacja + radioterapia −61.3%) oraz wyniki (wznowa miejscowa −15.9%, wznowa węzłowa −18.5%, przeżycia 3-letnie 46%, przeżycia 5-letnie 35%). W ocenie roli czynnika genetycznego zastosowano 3 techniki: genotypowanie, test bleomycynowy i test kometkowy. U 24 chorych oznaczono polimorfizm genów metabolizmu kancerogenów oraz genów związanych z naprawą DNA. Stwierdzono częstsze niż w grupie pacjentów starszych występowanie następujących genotypów ryzyka: GSTM1 (-) współwystępujący z NAT2 4/6A oraz NAT2 4/6A oraz allelu ryzyka: NAT2 4; allel ryzyka CYP 1A1 4 występował rzadziej niż w grupie starszych, natomiast częstość występowania genotypu ryzyka XPD 35931AA w obu grupach była zbliżona. U 5 pacjentów oznaczono poziom niestabilności chromosomowej za pomocą testu bleomycynowego – stwierdzono zbliżone wartości współczynnika b/c w grupie pacjentów młodszych i starszych przy jednocześnie wyraźnie większym odsetku uszkodzonych komórek w grupie młodych dorosłych. W obu grupach zarówno wartość współczynnika b/c jak i procent uszkodzonych komórek były wyrażnie większe niż w grupie osób zdrowych. W grupie 7 pacjentów za pomocą techniki comet assay określono uszkodzenia spontaniczne i indukowane oraz zdolności naprawy DNA – stwierdzono wysoki i zbliżony w grupie pacjentów młodych i starszych poziom uszkodzeń DNA – zarówno spontanicznych i indukowanych oraz zbliżone zdolności naprawy DNA

The effects of experimental administration of low doses of zearalenone on the histology of ovaries in pre-pubertal bitches

The experiment involved 30 clinically healthy Beagle bitches aged approximately 70 days with an initial body weight of approximately 8 kg. The animals were randomly divided into two experimental groups (EI and EII) and a control group of 10 animals each. Group EI was administered 50 μg of body weight zearalenone/kg per os for 42 days, group EII received 75 μg of body weight zearalenone/kg per os for 42 days, and the control group was administered placebo per os for 42 days. The bitches were ovariectomized at the end of the treatment period for anatomopathological examination. At the same time, peripheral blood samples were collected for endocrinological analyses (17β-estradiol and progesterone). Administartion of zearalenone particularly higher doses, resulted in the hyperestrogenism degeneration and atrophy of ovarian cells and tissues with accompanying edema and blood extravasation, leading to increased 17β-estradiol concentrations and an insignificant decrease in progesterone levels

Multi-mycotoxicosis

Contamination of food and feeds with mycotoxins is a major problem of human and animal's health concern, and it is also extremely detrimental to economy. Mycotoxin-producing moulds may produce the most known mycotoxins, such as aflatoxins, ochratoxin, trichothecenes, zearalenone and fumonisin. Although toxicological, environmental and epidemiological studies have addressed the problem of these toxins one by one, more than one mycotoxin is found usually in the same contaminated commodities. That raises the incommensurable problem of multi-mycotoxicosis in which the respective metabolites are also involved. These mycotoxins bear potential toxicity leading to acute and chronic effects in humans and animals, depending on species. The mechanisms that lead to toxic effects, such as immune toxicity and carcinogenicity, are complex. The risk assessment for humans potentially exposed to multi-mycotoxins suffers very much from the lack of adequate food consumption data. Furthermore, for a given mycotoxin additive, synergism and antagonism with other mycotoxins found in the same food commodities are usually not taken into account

Dichlorodiphenyldichloroethylene (DDE) residue limit exceeded in pig tissues after feed-borne exposure to maximum allowed concentration

Monitoring of undesirable substances by the European Union indicates a presence of natural and anthropogenic pollutants in animal feed that may be of concern for the producers, as well as the veterinary services. Although the literature concerning toxicity of DDT (an insecticide widely used in the past) is extensive, less attention has been focused on the biological properties of DDE and its interactions with other contaminants. This study reports on the concentration profile of p,p’-DDE and two other ogranochlorines (p,p’-DDT, p,p’-DDD) in different tissues of immature gilts after 14, 28, and 42 days of oral exposure to p,p’-DDE alone (0.5mg·kg-1feed·day-1) and in mixture with naturally occurring mycotoxin zearalenone, ZEN (0.5+0.1mg·kg-1feed·day-1). The treatment resulted in a time-dependent accumulation of p,p’-DDE in fat-rich tissues. Although the pesticide’s concentration found in the adipose tissue exceeded the FAO/WHO maximum residue limit (5mg·kg-1 of fat), human dietary risk is little, as it requires a substantial consumption of such contaminated pork fat. Importantly, the high concentration of p,p’-DDE found in the adrenal glands suggests a threat to the animals’ health. Finally, a difference in the accumulation of p,p’-DDE was observed between the groups treated with this compound alone or in mixture with ZEN. This is most likely related to growth performance of the animals, altered by the endocrine disrupting activity of both compounds. Further research should evaluate the effects of p,p-DDE at the observed concentrations on the pigs’ health status and enable the studies of possible interactions with other environmental pollutants

Dichlorodiphenyldichloroethylene (DDE) residue limit exceeded in pig tissues after feed-borne exposure to maximum allowed concentration

Monitoring of undesirable substances by the European Union indicates a presence of natural and anthropogenic pollutants in animal feed that may be of concern for the producers, as well as the veterinary services. Although the literature concerning toxicity of DDT (an insecticide widely used in the past) is extensive, less attention has been focused on the biological properties of DDE and its interactions with other contaminants. This study reports on the concentration profile of p,p’-DDE and two other ogranochlorines (p,p’-DDT, p,p’-DDD) in different tissues of immature gilts after 14, 28, and 42 days of oral exposure to p,p’-DDE alone (0.5mg·kg-1feed·day-1) and in mixture with naturally occurring mycotoxin zearalenone, ZEN (0.5+0.1mg·kg-1feed·day-1). The treatment resulted in a time-dependent accumulation of p,p’-DDE in fat-rich tissues. Although the pesticide’s concentration found in the adipose tissue exceeded the FAO/WHO maximum residue limit (5mg·kg-1 of fat), human dietary risk is little, as it requires a substantial consumption of such contaminated pork fat. Importantly, the high concentration of p,p’-DDE found in the adrenal glands suggests a threat to the animals’ health. Finally, a difference in the accumulation of p,p’-DDE was observed between the groups treated with this compound alone or in mixture with ZEN. This is most likely related to growth performance of the animals, altered by the endocrine disrupting activity of both compounds. Further research should evaluate the effects of p,p-DDE at the observed concentrations on the pigs’ health status and enable the studies of possible interactions with other environmental pollutants

A Combined Metabolomic and Proteomic Analysis of Gestational Diabetes Mellitus

The aim of this pilot study was to apply a novel combined metabolomic and proteomic approach in analysis of gestational diabetes mellitus. The investigation was performed with plasma samples derived from pregnant women with diagnosed gestational diabetes mellitus (n = 18) and a matched control group (n = 13). The mass spectrometry-based analyses allowed to determine 42 free amino acids and low molecular-weight peptide profiles. Different expressions of several peptides and altered amino acid profiles were observed in the analyzed groups. The combination of proteomic and metabolomic data allowed obtaining the model with a high discriminatory power, where amino acids ethanolamine, l-citrulline, l-asparagine, and peptide ions with m/z 1488.59; 4111.89 and 2913.15 had the highest contribution to the model. The sensitivity (94.44%) and specificity (84.62%), as well as the total group membership classification value (90.32%) calculated from the post hoc classification matrix of a joint model were the highest when compared with a single analysis of either amino acid levels or peptide ion intensities. The obtained results indicated a high potential of integration of proteomic and metabolomics analysis regardless the sample size. This promising approach together with clinical evaluation of the subjects can also be used in the study of other diseases