15 research outputs found
Basic mechanisms of the cellular alterations in T-2 toxin poisoning: Influence on the choice and result of the therapy
T-2 mycotoxin, secondary metabolite of Fusarium fungi, is one of the most potent cytotoxic representatives of trichothecene mycotoxin type A. After ingestion, T-2 toxin affects actively dividing cells and irreversible post-mitotic cells. In our experiments, the best protective effects were produced by dexametasone (PI = 3.37) and different methylprednisolone formulations (PI = 2.43-2.64). Significant protective efficacy was shown by nimesulide (PI = 1.44) and N-acethyilcistein (PI = 1.29), but their values were higher in a combination with methylprednisolone (PI = 2.16-2.34). Radioprotector amifostine (WR-2721) expressed good protective effects (PI = 1.26) or/and different absorbent formulations, such as: activated charcoal (PI = 1.13) and various Min-a-zelĀ® powder compounds, which are a well known zeolite clinoptilolite absorbents. Among the five zeolite regimens investigated, only Min-a-zel PlusĀ® showed a significant protective effect (PI = 1.77). In summary, the steroidal anti-inflammatory drugs could be recommended as a regimen of choice for treatment of acute T-2 toxicosis while nonsteroidal anti-inflammatory compounds, different absorbent formulations and their combinations with antioxidants or radioprotectors could be important for the treatment of subacute and chronic T-2 toxin poisonings.T-2 mikotoksin, sekundarni metabolit gljivica iz roda Fusarium, jedan je od najtoksiÄnijih predstavnika trihotecenskih mikotoksina tipa A. Njegove osnovne osobine, prvenstveno velika stabilnost u prirodi, jeftina proizvodnja, teÅ”ka detekcija i joÅ” uvek nepostojanje adekvatnog antidota Äine ga veoma dobrim potencijalnim bojnim otrovom. Posle unoÅ”enja, u organizmu otrovane jedinke T-2 toksin se u Äelijama vezuje za receptore na ribozomima i pokreÄe seriju kaskadnih reakcija koje za posledicu imaju smanjenje stabilnosti gRNK i poveÄanu ekspresiju proinflamatornih gena koji su izmeÄu ostalog odgovorni za nastanak anoreksije, gubitak telesne mase imunosupresiju, autoimunih efekata i oÅ”teÄenje veÄine tkiva. ToksiÄno oÅ”teÄenje ciljnih organa, nastalo pod dejstvom T-2 toksina, posledica je njegovog citotoksiÄnog efekta na labilne Äelije i proinflamatornog efekta na stabilne Äelije u organizmu životinja i ljudi. S obzirom na napred iznete Äinjenice, jasno je Å”to je u naÅ”im istraživanjima najbolji terapijski efekat, kod akutnog trovanja T-2 toksinom, postignut primenom antiinflamatornih lekova steroidne strukture, prvenstveno deksametazona (ZI = 3,37) i razliÄitih oblika metilprednizolona (ZI = 2,43-2,64). Osim toga antiinflamatorni lekovi nesteroidne strukture ispoljili su znaÄajan terapijski efekat, nimesulid (ZI = 1,44) i N-acetlilcistein (ZI = 1,29), ali se njihovo zaÅ”titno dejstvo potencira u kombinaciji sa metilprednisolonom (ZI = 2,16-2,34). Terapijsku efikasnost ispoljili su radioprotektor amifostin (WR-2721) (ZI = 1,26) i/ili razliÄiti apsorbensi. Od primenjenih apsorbenasa, kao Å”to su aktivni ugalj (ZI = 1,13) i razliÄiti oblici Min-a-zel-aĀ®, najveÄi protektivni efekat ispoljio je Min-a-zel PlusĀ® oblik klinoptiolinskog zeolita (ZI = 1,77). Na osnovu prikazanih rezultata, a u skladu sa Äinjenicom da je citotoksiÄno i proinflamatorno dejstvo T-2 toksina u direktnoj srazmeri sa njegovom akutnom toksiÄnoÅ”Äu, u potpunosti je opravdano koriÅ”Äenje visokih doza antiinflamatornih lekova steroidne strukture u terapiji akutnog trovanja T-2 toksinom. Sa druge strane, u terapiji subakutnih ili hroniÄnih trovanja T-2 toksinom, preporuÄuje se upotreba antiinflamatornih lekova nesteroidne strukture, razliÄitih apsorbenasa, ili njihove kombinovane primene sa antioksidansima ili radioprotektorima
Antioxidant status in breast cancer patients of different ages after radiotherapy
In this study we investigated the effects of breast cancer radiotherapy on the antioxidant (AO) enzyme activities of copper, zinc superoxide dismutase (CuZnSOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR), as well as on the concentration of reduced glutathione (GSH) and lipid peroxides (LP) in blood of patients aged 45-58 years and older than 60 years. The results show that in blood of patients aged 45-58 years, radiotherapy increased the activities of CuZnSOD, CAT, and GR, as well as the concentration of GSH, without affecting the activity of GPx and concentration of LP. In patients older than 60 years, radiotherapy increased the activities of CuZnSOD and CAT, lowered the activity of GPx and concentration of GSH, and increased the concentration of LP. Our results indicate that the response to radiotherapy involves age-related impairment of AO capacity for elimination of H2O2, causing oxidative damage to blood cells. This suggests that cytotoxic effects of radiation on healthy tissues might be more pronounced during the aging of breast cancer patients, and should be considered in the further development of individualization protocols in cancer radiotherapy
The role of FasR/FasL system in pathogenesis of myeloprolyferative neoplasms
Mijeloproliferativne neoplazije (MPN) su hematoloÅ”ki maligniteti koji se karakteriÅ”u nekontrolisanom Äelijskom proliferacijom i poremeÄajem u procesu apoptoze. Sistem FasR/FasL je ukljuÄen u kontrolu apoptoze u razliÄitim tipovima Äelija. U ovom radu je izuÄavana uloga sistema FasR/FasL u patogenezi mijeloproliferativnih neoplazija. UporeÄena je ekspresija FasR i FasL izmeÄu pacijenata sa MPN (24) i zdravih kontrola koriÅ”Äenjem metode 'real-time' PCR. Detektovana je poveÄana ekspresija FasR kod pacijenata sa MPN. Nije utvrÄena razlika u ekspresiji FasL. Mutacija B617F u JAK2 genu, karakteristiÄna za MPN, je naÄena kod 13 od 24 pacijenta. Pokazano je da ekspresija FasR i FasL nije povezana sa prisustvom B617F JAK2 mutacije.Myeloproliferative neoplasms (MPN) are hematological malignancies characterized by uncontrolled cell proliferation and impaired apoptosis. The FasR/FasL system is involved in the control of apoptosis in different cell types. Here we have investigated the role of FasR/FasL in the pathogenesis of MPNs. We compared FasR/FasL expression between MPN patients (24) and healthy individuals using the real-time PCR assay. We found an increase of FasR expression in MPN patients. No difference was detected in FasL expression. Mutation V617F in the JAK2 gene, a hallmark of MPN, was detected in 13/24 patients. We found that neither FasR nor FasL expression were related to the presence of JAK2 V617F mutation
Case with triple-negative breast cancer shows overexpression of both cFOS and TGF-beta 1 in node-positive tissue
We present herein a case report style article on a rare advanced triple-negative breast cancer (TNBC) patient with 6-month disease-free interval, and 10-month overall survival. Our results demonstrate that the poor clinical outcome of this patient was associated with pronounced, more than fivefold higher, overexpression of both cFOS and TGF-beta 1 proteins in its metastatic nodal tissue extracts, when compared with the values of the two non-TNBC controls (with zero disease-free interval and overall survival). This original observation suggests, for the first time, that both the cFOS and TGF-beta 1 may be considered as a pair of biomarkers for an early assessment of poor prognosis for TNBC patients. The possible clinical implication of this observation is discussed
Antioxidative enzymes in irradiated rat brain-indicators of different regional radiosensitivity
Purpose Previously, we examined manganese superoxide dismutase (MnSOD),
copper-zinc superoxide dismutase (CuZnSOD), and catalase (CAT)
activities in rat brain irradiated with 2 or 3 Gy of gamma-rays. The
results indicated that lower MnSOD activity and inducibility found in
hippocampus might explain higher radiosensitivity of this brain region.
Thus, in this study, we wanted to determine changes of MnSOD, CuZnSOD,
and CAT activities after dose of 5 Gy and to find out if differences in
MnSOD activity are caused by changes in its expression.
Heads of 4-day-old female rats were irradiated with gamma-rays, using
Co-60. Animals were sacrificed 1/24 h after exposure. Hippocampus and
cortex tissues were prepared for enzyme activity measurements and
Western blot analysis.
One hour after exposure, gamma-rays significantly decreased MnSOD
activity in both examined brain regions. Twenty-four hours later, MnSOD
recovery showed dose and regional dependence. It was weaker at higher
doses and in hippocampal region. MnSOD expression changed in the similar
manner as MnSOD activity only at lower doses of gamma-rays. In both
examined brain regions, gamma radiation significantly decreased CuZnSOD
activity and did not change activity of CAT.
Our results confirmed that MnSOD plays an important role in different
regional radiosensitivity but also showed that depending on dose,
radiation affects MnSOD level by utterly different mechanisms.
Postradiation changes of CuZnSOD and CAT are not regionally specific and
therefore, cannot account for the different radiosensitivity of the
hippocampus and cortex.Ministry of Education, Science and Technological Development {[}41027,
41022
Genomic profiling supports the diagnosis of primary ciliary dyskinesia and reveals novel candidate genes and genetic variants.
Primary ciliary dyskinesia (PCD) is a rare inherited autosomal recessive or X-linked disorder that mainly affects lungs. Dysfunction of respiratory cilia causes symptoms such as chronic rhinosinusitis, coughing, rhinitis, conductive hearing loss and recurrent lung infections with bronchiectasis. It is now well known that pathogenic genetic changes lead to ciliary dysfunction. Here we report usage of clinical-exome based NGS approach in order to reveal underlying genetic causes in cohort of 21 patient with diagnosis of PCD. By detecting 18 (12 novel) potentially pathogenic genetic variants, we established the genetic cause of 11 (9 unrelated) patients. Genetic variants were detected in six PCD disease-causing genes, as well as in SPAG16 and SPAG17 genes, that were not detected in PCD patients so far, but were related to some symptoms of PCD. The most frequently mutated gene in our cohort was DNAH5 (27.77%). Identified variants were in homozygous, compound heterozygous and trans-heterozygous state. For detailed characterization of one novel homozygous genetic variant in DNAI1 gene (c. 947_948insG, p. Thr318TyrfsTer11), RT-qPCR and Western Blot analysis were performed. Molecular diagnostic approach applied in this study enables analysis of 29 PCD disease-causing and related genes. It resulted in mutation detection rate of 50% and enabled discovery of twelve novel mutations and pointed two possible novel PCD candidate genes
Extended time of cold ischemia and its influence on the physiological function of human adult pancreatic islets
In this study we compared the effects of duration of cold ischemia (longer and shorter ischemia) on the yield, viability and preservation of the physiological function and insulin secretion of adult human pancreatic islets in short-term (seven days) culture. Based on the tested parameters, we established that there are no major differences between these two test groups and that the storage and transport of pancreatic tissue in physiological solution at 4 degrees C gives quite satisfactory results