Multi-scale fractal Fourier Ptychographic microscopy to assess the dose-dependent impact of copper pollution on living diatoms.

Accumulation of bioavailable heavy metals in aquatic environment poses a serious threat to marine communities and human health due to possible trophic transfers through the food chain of toxic, non-degradable, exogenous pollutants. Copper (Cu) is one of the most spread heavy metals in water, and can severely affect primary producers at high doses. Here we show a novel imaging test to assay the dose-dependent effects of Cu on live microalgae identifying stress conditions when they are still capable of sustaining a positive growth.

Identification of a Green Algal Strain Collected from the Sarno River Mouth (Gulf of Naples, Italy) and Its Exploitation for Heavy Metal Remediation.

Heavy metals (HMs) can induce both chronic and acute harmful effects on marine and freshwater biota. The environmental impact of HMs in freshwater, seawater, soil, and wastewater can be limited using microbes, including microalgae, that are able to remove metals from environmental matrices. Indeed, they can passively adsorb and actively accumulate these persistent pollutants within their organelles, limiting their detrimental effects on cellular metabolism.

Copper Effect on Microalgae: Toxicity and Bioremediation Strategies.

Microalgae are increasingly recognised as suitable microorganisms for heavy metal (HM) removal, since they are able to adsorb them onto their cell wall and, in some cases, compartmentalise them inside organelles. However, at relatively high HM concentrations, they could also show signs of stress, such as organelle impairments and increased activities of antioxidant enzymes. The main aim of this review is to report on the mechanisms adopted by microalgae to counteract detrimental effects of high copper (Cu) concentrations, and on the microalgal potential for Cu bioremediation of aquatic environments.

Kinematic analysis and visualization of Tetraselmis microalgae 3D motility by digital holography.

A study on locomotion in a 3D environment of Tetraselmis microalgae by digital holographic microscopy is reported. In particular, a fast and semiautomatic criterion is revealed for tracking and analyzing the swimming path of a microalga (i.e.

The tyrosine kinase inhibitor E-3810 combined with paclitaxel inhibits the growth of advanced-stage triple-negative breast cancer xenografts.

E-3810 is a novel small molecule that inhibits VEGF receptor-1, -2, and -3 and fibroblast growth factor receptor-1 tyrosine kinases at nmol/L concentrations currently in phase clinical II. In preclinical studies, it had a broad spectrum of antitumor activity when used as monotherapy in a variety of human xenografts. We here investigated the activity of E-3810 combined with different cytotoxic agents in a MDA-MB-231 triple-negative breast cancer xenograft model.

E-3810 is a potent dual inhibitor of VEGFR and FGFR that exerts antitumor activity in multiple preclinical models.

Tumor angiogenesis is a degenerate process regulated by a complex network of proangiogenic factors. Existing antiangiogenic drugs used in clinic are characterized by selectivity for specific factors. Antiangiogenic properties might be improved in drugs that target multiple factors and thereby address the inherent mechanistic degeneracy in angiogenesis.

ATP non-competitive Ser/Thr kinase inhibitors as potential anticancer agents.

Protein kinases are one of the largest known families of enzyme characterized by having a well conserved ATP binding pocket. Most of the synthetic kinase inhibitors are ATP-competitive, but display some potential problems, like selectivity, discrepancy between the in vitro and in vivo inhibition assays and an high risk of developing mutation inside the ATP-binding pocket. Recently some new inhibitors with a non-competitive mechanism of action were reported, with interesting results both in vitro and in vivo.

Pixantrone (BBR 2778) has reduced cardiotoxic potential in mice pretreated with doxorubicin: comparative studies against doxorubicin and mitoxantrone.

Anthracyclines and anthracenediones are important oncotherapeutics; however, their use is associated with irreversible and cumulative cardiotoxicity. A novel aza-anthracenedione, pixantrone (BBR 2778), was developed to reduce treatment-related cardiotoxicity while retaining efficacy. This study evaluates the cumulative cardiotoxic potential of pixantrone compared with equiactive doses of doxorubicin and mitoxantrone in both doxorubicin-pretreated and doxorubicin-naïve mice.

Effects of pixantrone on immune-cell function in the course of acute rat experimental allergic encephalomyelitis.

Pixantrone is an immunesuppressor similar to mitoxantrone but with lower cardiotoxicity. We evaluated the effect of pixantrone on B cells and lymphomononuclear cells in the course of acute EAE. Pixantrone reduced the number of B cells and suppressed myelin basic protein (MBP) specific IgG production.

Pixantrone (BBR2778) reduces the severity of experimental allergic encephalomyelitis.

Pixantrone is less cardiotoxic and is similarly effective to mitoxantrone (MTX) as an antineoplastic drug. In our study, pixantrone reduced the severity of acute and decreased the relapse rate of chronic relapsing experimental allergic encephalomyelitis (EAE) in rats. A marked and long-lasting decrease in CD3+, CD4+, CD8+ and CD45RA+ blood cells and reduced anti-MBP titers were observed with both pixantrone and MTX.

Bbr 2778, an aza-anthracenedione endowed with preclinical anticancer activity and lack of delayed cardiotoxicity.

With the aim to provide second-generation anthracenedione analogues endowed with reduced side effects and a wider spectrum of action than mitoxantrone and doxorubicin, a large number of new molecules bearing nitrogen atoms in the chromophore was synthesized and screened in vitro and in vivo. From this screening, BBR 2778 (6,9-bis[(2-aminoethyl)amino] benzo[g]isoquinoline-5,10-dione dimaleate) emerged as the most interesting compound. BBR 2778 was tested in vitro on several murine and human tumor cell lines and showed cytotoxic potency lower than that of mitoxantrone and doxorubicin.

Effect on the peripheral nervous system of systemically administered dimethylsulfoxide in the rat: a neurophysiological and pathological study.

The issue of dimethylsulfoxide (DMSO) neurotoxicity is an important one, given its wide use in experimental toxicology as a solvent for hydrophobic substances. We examined the effect of the intraperitoneal administration of different DMSO solutions (1.8-7.

BBR 3464: a novel triplatinum complex, exhibiting a preclinical profile of antitumor efficacy different from cisplatin.

Multinuclear platinum complexes represent a new class of anticancer agents, distinct in terms of DNA binding features and the profile of antitumor activity from their mononuclear counterparts, in particular cisplatin. Among complexes of this class, BBR 3464, a trinuclear platinum compound has been selected for preclinical development. In the present study, we describe the preclinical evaluation of BBR 3464 in a series of human tumor cell lines and tumor xenografts, with special emphasis on tumor types known to be resistant to cisplatin.

Distribution of paclitaxel within the nervous system of the rat after repeated intravenous administration.

The distribution of paclitaxel (Taxol) within the central and peripheral nervous system after repeated administration of this antineoplastic agent is still largely unknown. In this study we determined for the first time paclitaxel tissue concentration in the brain, spinal cord, dorsal root ganglia (DRG) and sciatic nerve using an experimental paradigm in the rat which reproduces the features of paclitaxel peripheral neurotoxicity in humans. Pathological confirmation of the onset of paclitaxel-induced peripheral neurotoxicity was performed.

Hyperkeratosis-associated coryneform infection in severe combined immunodeficient mice.

Hyperkeratosis-associated coryneform (HAC) is a coryneform bacterium, with a biochemical profile similar to Corynebacterium bovis, that causes hyperkeratotic dermatitis in athymic nude mice. In the present study 28 severe combined immunodeficient (SCID) mice coming from six different animal facilities were submitted for bacteriological and pathological examination. HAC was isolated from 10 SCID mice belonging to two of these facilities.

Outbreaks of hyperkeratotic dermatitis of athymic nude mice in northern Italy.

Hyperkeratotic dermatitis of athymic nude mice is an infectious disease caused by a coryneform bacterium. During the spring of 1995, outbreaks of hyperkeratotic dermatitis were observed in several nude mice facilities in northern Italy. In this report we describe the clinical, histopathological and microbiological features of the disease in two different animal facilities.

Effect on the peripheral nervous system of the short-term intravenous administration of paclitaxel in the rat.

The effectiveness of paclitaxel (Taxol) in the treatment of different tumors is well-known but, on the other hand, there is little information regarding its neurotoxicity and the mechanism(s) underlying this potentially severe side effect. In this study, using behavioral, neurophysiological, morphological and morphometric methods, we evaluated the effect of intravenous administration of paclitaxel on the rat nervous system. After 2 pilot studies, 40 female Wistar rats were treated with intravenous paclitaxel via a catheter placed in the jugular vein, while 20 animals were used as controls.

Comparative toxicology of two enantiomers of the peripherally acting non-narcotic antitussive drug moguisteine.

Moguisteine (R,S(+/-)-2-(2-methoxyphenoxy)-methyl-3-ethoxycarbonylacetyl-1,3-t hiazolidine, CAS 119637-67-1), a new peripheral non-narcotic antitussive drug, is a racemate composed of an equimolar mixture of R(+) and S(-) enantiomers (BBR 2221 and BBR 2222, respectively). Since in some cases the use of only one enantiomer instead of a racemate may increase the efficacy and/or the tolerability of a compound, moguisteine enantiomers were submitted to toxicological evaluation. Given in a single oral (gavage) or intraperitoneal administration to mice and rats, both moguisteine enantiomers show very low general toxicity.

Antitussive activity of moguisteine enantiomers in guinea-pigs and rats.

The antitussive effect of the R-(+)- and S-(-)-enantiomers of moguisteine were evaluated in comparison with the racemate in cough induced by 7.5% citric acid and 30 microM capsaicin aerosol in conscious guinea-pigs. No difference in potency was observed between moguisteine and the enantiomers.

Leptospira interrogans serovar sejroe infection in a group of laboratory dogs.

Interstitial nephritis was seen histologically in 19 (59%) out of 32 pure-breed beagle dogs (16 males and 16 females) subjected to standard safety tests. In these animals no clinical abnormalities were observed and all the tested parameters (haematology, biochemistry and urine analysis) were within the normal ranges. Leptospiral antibody titres ranging from 1 : 100 to 1 : 6400, against a serovar (hardjo) belonging to the Sejroe serogroup, were detected by the microscopic agglutination test (MAT) in the serum of the 19 dogs with interstitial nephritis.

Reproductive toxicology of the new antitussive moguisteine.

Moguisteine (R,S(+/-)-2-(2-methoxyphenoxy)-methyl-3-ethoxycarbonylacetyl- 1,3-thiazolidine, CAS 119637-67-1), a new oral non narcotic peripherally acting antitussive drug, was examined for effects in the rat on general reproductive performance (at 0, 50, 212, 900 mg/kg/d,) for embryotoxicity (at 0, 25, 75, 225, 900 mg/kg/d) and for peri-postnatal toxicity (at 0, 62.5, 250, 1000 mg/kg/d). Embryotoxicity (at 0, 75, 225, 900 mg/kg/d) was also examined in the New Zealand White rabbit.

General toxicology of the new antitussive moguisteine.

Moguisteine (R,S(+/-)-2-(2-methoxyphenoxy)-methyl-3-ethoxycarbonylacetyl- 1,3-thiazolidine, CAS 119637-67-1), a new oral non-narcotic peripherally acting antitussive drug, was submitted to toxicological evaluation. The oral (gavage) and intraperitoneal routes in mice and rats and the oral route in rabbits produce very low acute toxicity. Administered by oral route, moguisteine proved to be well tolerated for 26 consecutive weeks and did not induce any general or local effect at up to the respective doses of 240 and 60 mg/kg/day for rats and dogs.

Acute intravenous toxicity of dimethyl sulfoxide, polyethylene glycol 400, dimethylformamide, absolute ethanol, and benzyl alcohol in inbred mouse strains.

Acute intravenous toxicity of some solvents, i.e. dimethyl sulfoxide (DMSO), polyethylene glycol 400 (PEG 400), dimethylformamide (DMF), absolute ethanol (EtOH) and benzyl alcohol (BeOH), was determined in three inbred (CD2F1, B6D2F1 and C57BL/6N) mouse strains used in many preclinical tests, mainly in oncology and toxicology.

Efficacy of glutathione for treatment of fascioliasis. An investigation in the experimentally infested rat.

Liver fluke infection (Fasciola hepatica) depresses the drug-metabolizing capacity of the hepatic mixed function oxidase (MFO) and glucuronosyltransferase (GT) enzyme systems, throughout a free radicals mediated lipid peroxidation process. Glutathione (GSH, CAS 70-18-8) administered chronically (100 mg/kg i.p.