Hair has been shown to be an excellent site for the accumulation of different drugs including Delta *b-agonists, and therefore, it would be an appropriate matrix for surveillance for the presence of ...drug residues. The aim of this study was to determine concentrations and to compare accumulation of two different Delta *b-agonists in black and white mice hair by use of ELISA as a screening quantitative method. The study included 200 8-week-old white and black mice. One group of black mice and one group of white mice were treated with clenbuterol in a dose of 2.5 mg/kg body mass per os for 28 days. Other animals were treated in the same way with salbutamol. The highest (?SD) clenbuterol concentration of 631.4 ? 23.5 ng/g in black hair and 228.5 ? 156.2 ng/g in white hair was determined on day 1 of treatment withdrawal. Study results revealed the black-to-white hair ratio of clenbuterol accumulation to be 1:2-1:4 and of salbutamol accumulation 1:1.4. The mean (?SD) salbutamol concentrations determined on day 1 of treatment withdrawal was 23.9 ? 0.9 ng/g and 16.4 ? 1.1 ng/g in black and white hair samples, respectively. The study demonstrated that residues could be determined in hair samples even after a 30-day withdrawal period.
Aims and background
The aim of the study was to investigate whether use of the antiestrogen tamoxifen and heat treatment in combined therapy with the well-known anticancer drugs cisplatin, ...dacarbazine and cyclophosphamide enhances their therapeutic efficacy on mouse B16-F10 melanoma in vivo. The results of systemic melanoma therapy have been mostly disappointing. Therefore, there is still a great need for strategies that can improve existing chemotherapy options.
Methods and study design.
The tumor model for the investigation of antitumor activity was a mouse B16–F10 melanoma transplanted into the footpad of C57BL/6 Zgr/Hr mice. Drugs were given intraperitoneally 15 min before the application of local hyperthermia, and tumor growth and mouse survival were followed.
Results
Hyperthermia alone determined a significant delay of tumor growth, but mouse survival was not affected. In bimodal combinations with hyperthermia, all the tested antitumor drugs significantly increased both tumor growth delay and mouse survival. Tamoxifen alone did not show any inhibitory effect on B16–F10 melanoma in vivo. However, in the trimodal therapy with a particular drug and hyperthermia, it potentiated the inhibitory effects of the respective bimodal treatments, especially that of cyclophosphamide and hyperthermia.
Conclusions
Our results obtained on the mouse B16–F10 melanoma in vivo confirmed the enhanced therapeutic efficacy of the trimodal therapy tamoxifen, hyperthermia and anticancer drug combinations in melanoma treatment. Further studies should optimize the heat-drug time scheduling and drug doses that will result in the best possible therapeutic achievement for these trimodal therapy options.
Changes in blood flow velocity through the tumors can induce damage of tumor microcirculation and thus may contribute to the final destruction of tumor masses after photodynamic therapy (PDT). The ...aim of this study was to evaluate the blood flow changes in a SCCVII mouse carcinoma during Photofrin-based photodynamic therapy by analyzing several quantitative spectral Doppler parameters maximum systolic flow velocity (Vmax), end diastolic velocity (Vmin), resistance index (RI) and pulsatile index (PI) by using the color Doppler ultrasonography. Blood flow velocities were recorded immediately prior to tumor illumination (0 h) and then 2 and 24 h after the illumination. Statistically significant increase in diastolic blood velocity (Vmin) with a corresponding decline in RI and PI was recorded in tumors of the Photofrin-injected mice prior to tumor illumination. However, 2 h after the illumination a pronounced decrease in both Vmin and Vmax was obtained. There were no changes of these parameters in controls at different times during determination. The observed changes of spectral Doppler parameters in tumors from the PDT group point to the transition of tumor blood vessels from the relaxation state recorded before tumor illumination into a state of increased contraction after the activation of Photofrin by light. Pronounced changes in tumor blood vessel tone might be an additional stress for such vessels leading to their ultimate destruction.
The dynamics of SCCVII transplantable tumor growth in C3H/H mice was determined after local tumor irradiation and/or virus (NDV LaSota) i.p. injection. The virus applied alone significantly ...suppressed tumor growth, particularly until the 19th day after tumor transplantation. Local irradiation with 30 Gy resulted in tumor disappearance followed
with its regrowth about 15 days later. However, if the virus was injected after the irradiation, there was no tumor growth until the end of the 31 day observation period. It should be noted that virus application prior to local irradiation did not have any additional influence on tumor growth. Thus, the pronounced efficacy of virus applied after tumor irradiation deserves attention. It is possible that the virus injected after irradiation induced a chain of cytokine production joining the action of tumor destruction induced by irradiation. This should be further studied in clarifying the approaches to combined tumor therapy with possible cell-free vaccine production.
Two kinds of nanosize V sub(2)O sub(5) particles were synthesized in our own laboratory and concomitantly applied to V79 and L929 fibroblasts and SCCVII, B16F10 and FsaR tumor cells. The morphologies ...of the cells were monitored using an inverted inverse microscope equipped with digital camera, while quantitative determination of the cytotoxicity of nanosize V sub(2)O sub(5) particles was measured using crystal violet bioassay. Twenty four hours after the addition of nanosize V sub(2)O sub(5) particles (20 mu M), noticeable changes in the morphology and density of fibroblast and cancer cells were observed. Reculturing in a freshly prepared medium for the next 24 h showed a high recovery effect on V79, SCCVII and B16F10 cells, while FsaR and L929 cells were seriously damaged and unable to recover. At a higher concentration of nanosize V sub(2)O sub(5) particles (100 mu M), the cytotoxicity of V sub(2)O sub(5) prevailed against the recovery effect in all cell types. Quantitative measurements have shown that the resistance of investigated cell cultures to the cytotoxicity of nanosize V sub(2)O sub(5) particles decreases in the order V79 > SCCVII > B16F10 > FsaR > L929. The high cytotoxic effect found on FsaR cells suggests that nanosize V sub(2)O sub(5) particles could be regarded as poisoning material in the treatment of FsaR fibrosarcoma cells. Possible mechanisms involved in the cytotoxicity of nanosize V sub(2)O sub(5) particles were discussed.
Nearomatski visokosteranski naftalan (NAVS) posebna je frakcija hrvatske nafte, iznimno bogata steranima, iz koje je odstranjen aromatski sastav. Steranima se pripisuje bioaktivnost slična steroidnim ...hormonima, modulatorima tumorskoga rasta. Potaknuti rezultatima prijašnjih in vitro i in vivo studija o inhibitornom efektu NAVS-a na rast planocelularnog karcinoma, proveli smo studiju o njegovu učinku na oralni planocelularni karcinom (OPCC) u miševa.
Ciljevi: 1) ispitati valjanost jednostavnog eksperimentalnog modela OPCC-a; 2) ispitati mogući antiproliferativni učinak NAVS-a na postavljenome modelu praćenjem tumorskoga rasta; 3) ispitati antineoangiogeni učinak NAVS-a kao objašnjenje mogućeg antiproliferativnog učinka, te za tu prigodu procijeniti mogućnost križne reaktivnosti anti-humanih imunohistokemijskih markera s mišjim tkivom. Suspenzija od 100 μl s 105 SCC VII stanica inokulirana je intraoralnim putem pod bukalnu sluznicu u 48 singeničnih C3H miševa. Sedam dana nakon inokulacije životinje su podijeljene u 6 jednakih skupina, te se miševima, ovisno o skupini, intratumorski injiciralo po 100 μl sljedećih tvari: parafinsko ulje (PO) kao negativna kontrola, NAVS (u jednoj skupini 7 dana, a u drugoj skupini 14 dana nakon inokulacije tumora), 1, 25 dihidroksiergotamin (1,25-D3) kao pozitivna kontrola, te kombinacije NAVS s 1,25-D3 i PO s 1,25-D3. Rast tumora praćen je tjednim mjerenjem s pomoću kalipera. Životinje su žrtvovane 1., 2., 3. i 4. tjedna nakon aplikacije ispitivanoga sredstva. Histološki pripravci eksplantiranih tumora bojeni su hematoksilin-eozinom te imunohistokemijski s anti-CD34 protutijelima radi procjene tumorske neoangiogeneze. U usporedbi s PO skupinom, tumorski rast i angiogeneza bili su sniženi u 1,25-D3 i NAVS skupinama. NAVS vjerojatno smanjuje rast OPCC-a inhibicijom vaskularne proliferacije potrebne za tumorski rast.
Chemical analysis of plasma samples of wild fish from the Sava River (Croatia) revealed the presence of 90 different pharmaceuticals/illicit drugs and their metabolites (PhACs/IDrgs). The ...concentrations of these PhACs/IDrgs in plasma were 10 to 1000 times higher than their concentrations in river water. Antibiotics, allergy/cold medications and analgesics were categories with the highest plasma concentrations. Fifty PhACs/IDrgs were identified as chemicals of concern based on the fish plasma model (FPM) effect ratios (ER) and their potential to activate evolutionary conserved biological targets. Chemicals of concern were also prioritized by calculating exposure-activity ratios (EARs) where plasma concentrations of chemicals were compared to their bioactivities in comprehensive ToxCast suite of in vitro assays. Overall, the applied prioritization methods indicated stimulants (nicotine, cotinine) and allergy/cold medications (prednisolone, dexamethasone) as having the highest potential biological impact on fish. The FPM model pointed to psychoactive substances (hallucinogens/stimulants and opioids) and psychotropic substances in the cannabinoids category (i.e. CBD and THC). EAR confirmed above and singled out additional chemicals of concern - anticholesteremic simvastatin and antiepileptic haloperidol. Present study demonstrates how the use of a combination of chemical analyses, and bio-effects based risk predictions with multiple criteria can help identify priority contaminants in freshwaters. The results reveal a widespread exposure of fish to complex mixtures of PhACs/IDrgs, which may target common molecular targets. While many of the prioritized chemicals occurred at low concentrations, their adverse effect on aquatic communities, due to continuous chronic exposure and additive effects, should not be neglected.
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•Ninety pharmaceuticals/illicit drugs and their metabolites were analyzed.•Fish plasma model and ToxCast data were used to identify chemicals of concern.•Nicotine, cotinine, prednisolone and dexamethasone: chemicals of concern.•Fish plasma model pointed psychoactive chemicals as potentially hazardous to fish.
Increased contamination of aquatic ecosystems with pharmaceuticals could have been expected due to the COVID-19 pandemic. Surface water from three domains (rural, semirural, urban) of the Mrežnica ...River (Croatia) was screened for 253 pharmaceuticals by SPE-UHPLC-MS/MS. At the beginning of the pandemic, the highest concentration of drugs (excluding veterinary) was detected at urban site (291.4 ng/L), followed by semirural (186.5 ng/L) and rural (141.6 ng/L). With the progression of pandemic, contamination increase was observed at all sites, but it was the most obvious at semirural (approximately 400–700 ng/L). The most pronounced concentration increases were observed for non-opioid analgesics, especially ibuprofen. In September 2021, the first notable occurrence of opioid analgesics was recorded. The most represented group of pharmaceuticals at the start of the pandemic (May 2020) was generally stimulants (caffeine, cotinine). In September 2021, the predominant group was analgesics at all sites (45–84%), whereas stimulants decreased to undetectable levels. The results of this study indicated that the epidemiological measures and medical treatments that were widely imposed/applied caused notable increase of the surface water contamination with drugs of a small river with limited dilution capacity, indirectly pointing to the changes that occurred in the behaviour and habits of the inhabitants of the affected areas.
The remnants of historical industrial contamination can be detected in many aquatic ecosystems worldwide even at present time. Mrežnica is a river in Croatia that has been, for more than a hundred ...years, continually exposed to effluents of various industries, which have, in modern time, mostly ceased to operate. Our aim was to establish the level of current contamination and pollution of the Mrežnica river-water and sediments. The study of river contamination at three sites (reference site; site nearby former cotton industry facility in Duga Resa – DRF; industrial zone of Karlovac town - KIZ) in three sampling campaigns (May 2020, April and September 2021) encompassed analyses of physico-chemical water parameters, screening of 369 pesticides, measurement of metal (loid) concentrations in the sediments, and in the dissolved and particulate phases of the river-water. The sediment pollution was assessed through the analyses of total bacteria abundance (by targeting 16S rRNA genes), and their associated metal resistance genes (cnrA, pbrT and czcD) and class 1 integrons (intl1). At the DRF site, industrial organic contaminants that can be traced to textile production were detected (dye and nylon components), as well as increased levels of some metals bound to suspended particulate matter and sediments. At the most downstream KIZ site, occasional high level of industrial herbicide neburon was measured in the river-water, and metal contamination of suspended particulate matter and sediments was evident. Although, based on the comparison with legislation and literature data, the level of contamination was rather mild, the effects on microbial communities were unquestionable, confirmed by increased abundance of the czcD gene at DRF site and the intI1 gene at both industrially impacted sites. Obtained results indicated long-term sediment retention of some industrial contaminants at the places of historical freshwater contamination, and, thus, the necessity for their monitoring even after the termination of contamination sources.
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•The remnants of historical contamination detected in freshwater ecosystem.•Dye and nylon components found in river-water near former cotton industry facility.•High levels of industrial herbicide detected in water near urban industrial zone.•River mildly contaminated with metals at sites of past long-term industrial impact.•Pollution biomarker, microbial gene intI1, higher at industrially impacted sites
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