Molecular docking,a tool to determine interaction of CuO and TiO2 nanoparticles with human serum albumin

BackgroundWe study the human serum albumin (HSA) protein-CuO nanoparticle interaction to identify the specific binding site of protein with CuO nanoparticles by molecular docking and compared it with HSA-TiO₂ nanoparticle interaction.MethodsThe protein structural data that was obtained using Autodock 4.2.ResultsIn case of CuO np-HSA interaction, the distances from the centre of Subdomain IIIA to Arg-472 is 2.113 Å and Lys 475, Glu 492, Ala 490, Cys 487, Ala 490 are the bound neighbouring residues with Lys 475, Glu 492 at aliphatic region. The binding energy generated was ?1.64 kcal mol^?1. However, for TiO₂ nanoparticle, the binding region is surrounded by Arg 257, Ala 258, Ser 287, His 288, Leu 283, Ala 254, Tyr 150 (subdomain II A) as neighbouring residue. Moreover, Glu 285, Lys 286 forms aliphatic grove for TiO₂-HSA, Ser-287 at the centre region form hydrogen bond with nanoparticle and Leu 283, Leu 284 forming hydrophopobic grove for TiO₂ nanoparticle-HSA interaction. The binding energy generated was ?2.47 kcal mol^?1.ConclusionsAnalysis suggests that CuO bind to suldow site II i.e subdomain III A of HSA protein where as TiO₂ nanoparticle bind to suldow site I i.e subdomain IIA of HSA protein.General significanceThe structural information that derives from this study for CuO and TiO₂ nanoparticles may be useful in terms of both high and low-affinity binding sites when designing these nanoparticles based drugs delivery system.     

Release and inhibitory effects of prostaglandin D2 in guinea pig urinary bladder and the role of urothelium

BackgroundWhile studying a urothelium-derived inhibitory factor in guinea pig urinary bladders we observed considerable release of prostanoids, including PGD₂-like activity. The present study was carried out to identify the prostanoids and to study their roles in modulating guinea pig urinary bladder motility.MethodsRelease of PGE₂ and PGD₂ in isolated guinea pig urinary bladder preparations was analyzed by high performance liquid chromatography (HPLC) combined with bioassay on bladder strips. Isolated urothelium-intact (UI) or -denuded (UD) bladder strips were subjected to electrical field stimulation (EFS) and applications of PGE₂ and PGD₂.ResultsA resting release of 95 ± 9 (n = 5) ng g tissue^− 1 h^− 1 PGE₂-like activity and 210 ± 34 (n = 4) ng g tissue^− 1 h^− 1 PGD₂-like activity was found, where PGD₂-like was subject to marked spontaneous inactivation during isolation. Prostanoids release was decreased by 70–90% by the cyclo-oxygenase inhibitor diclofenac in UI preparations. Urothelium removal decreased prostanoids release by more than 90%.PGE₂ increased basal tone and spontaneous contractions, whereas PGD₂ had little or no effect on these. Exogenous PGE₂ enhanced and PGD₂ inhibited contractile responses to EFS, exogenous acetylcholine- and ATP, whereas PGD₂ caused marked dose-dependent inhibition. PGE₂ and PGD₂ effects were more pronounced in diclofenac-treated UD tissues.ConclusionsPGD₂ and PGE₂ are released from guinea pig bladder urothelium and PGD₂ has inhibitory effects on bladder motility, mainly through a postjunctional action on smooth muscle responsiveness.General significanceThe release and inhibitory effects merit further studies in relation to normal biological function as well as overactive bladder syndrome.     

Postoperative endometrial carcinoma treated with external beam irradiation plus vaginal-cuff brachytherapy. Is there a dose relationship with G2 vaginal complications?

AimTo analyse the possible relationship between the EQD2_(α/β=3Gy) at 2 cm³ of the vagina and late toxicity in vaginal-cuff-brachytherapy (VBT) after external-beam-irradiation (EBRT) for postoperative endometrial carcinoma (EC).Materials and methodsFrom 2014 to 2016, 62 postoperative EC patients were treated with EBRT + VBT. The median EBRT dose was 45 Gy (44 Gy–50.4 Gy). VBT involved a single 7 Gy dose. Toxicity was prospectively evaluated using the RTOG score for the rectum and bladder and the objective LENT-SOMA criteria for the vagina. EQD2_{(α/β = 3Gy)} at 2 cm³ of the most exposed part of the vagina was calculated by the sum of the EBRT + VBT dose. Statistics: Boxplot, Student’s t and Chi-square tests and ROC curves.ResultsMean follow-up: 39.2 months (15–68). Late toxicity: bladder:0 patient; rectum:2 patients-G1; Vagina: 26 patients-17G1, 9G2; median EQD2_(α/β=3Gy) at 2 cm³ in G0-G1 patients was 70.4 Gy(SD2.36), being 72.5 Gy(SD2.94) for G2p. The boxplot suggested a cut-point identifying the absence of G2: 100 % of G2p received >68 Gy, ROC curves showed an area under the curve of 0.72 (sensitivity of 1 and specificity of 0.15).ConclusionsDoses >68 Gy EQD2_(α/β=3Gy) at 2 cm³ to the most exposed area of the vagina were associated with late G2 vaginal toxicity in postoperative EC patients treated with EBRT + VBT suggesting a very good dose limit to eliminate the risk of G2 late toxicity. The specificity obtained indicates the need for prospective analyses.     

High intensity interval exercise decreases IL-8 and enhances the immunomodulatory cytokine interleukin-10 in lean and overweight–obese individuals

PurposeTo compare the effects of two interval exercises with different intensities on acute inflammatory response in lean and overweight–obese subjects.MethodsTen lean (BMI < 24.9 kg/m²) and 12 overweight–obese (BMI 25 to <34.9 kg/m²) males performed two conditions in randomly assigned: (1) high intensity interval exercise (HIIE) 10 × 60 s (85–90%P_Max)/75 s (50%P_Max); (2) moderate intensity interval exercise (MIIE) 10 × 60 s (70–75%P_Max)/60 s (50%P_Max), with blood collections at pre, immediately and 30 min post each exercise bouts to evaluate total and differential leukocyte counts, serum creatine kinase (CK), lactate dehydrogenase (LDH) and systemic levels of IL-1ra, IL-6, IL-8, IL-10, IL-17a and CCL2.ResultsIn lean group, HIIE induced a significant increase in total leukocytes and monocyte, while MIIE session did not change the number of leukocytes. Overweight–obese group presented similar increase in leukocytes, monocytes and lymphocytes in both HIIE and MIIE sessions. At baseline, overweight–obese group showed high levels of CK, IL-8, IL-6 and CCL2 and lower concentrations of IL-10 compared to lean group. The MIIE did not alter the cytokine concentrations in both groups, independently of the time analysis. The HIIE induced significant decrease in IL-8 levels 30 min post session in both the groups, and a progressive elevation in IL-10 levels immediately and 30 min post in lean and overweight–obese. Regarding IL-6, overweight–obese subjects presented progressive increase either immediately and 30 min after HIIE, while lean individuals presented significant increase only 30 min after exercise.ConclusionsThe acute inflammatory response to interval exercise is intensity-dependent. Although obesity influences the basal concentrations of several cytokines, only HIIE induced important alterations in IL-8 and IL-10 levels, which may have important implications in the control of chronic low-grade inflammation in obesity.     

Acute effects of cocaine,morphine and their combination on bioenergetic function and susceptibility to oxidative stress of rat liver mitochondria

AimsCocaine and heroin are frequently co-abused in a combination known as speedball. Despite the relevance of the liver in the metabolism and detoxification of these drugs, little is known about the impact of speedball on liver function.Main methodsIn this work, we evaluated the effects of cocaine, morphine and morphine + cocaine (Mor + Coc) combination (1:1) in isolated rat liver mitochondria, upon glutamate/malate or succinate energization, on bioenergetics and oxidative stress-related parameters by using Clark O₂, Ca^2 +, TPP⁺ and pH electrodes and by measuring thiobarbituric acid reactive substances (TBARS) and H₂O₂ production.Key findingsCocaine and Mor + Coc at the higher concentrations (1 mM) similarly increased O₂ consumption at state 2, state 4 and state oligomycin. In these conditions, maximum respiration was decreased only upon glutamate/malate energization, suggesting an involvement of complex I. Morphine (1 mM) only increased state 2 respiration. Cocaine and Mor + Coc induced a similar decrease in maximum mitochondrial membrane potential and in ADP-induced depolarization, whereas morphine had no effect. The drugs and their combination similarly decreased mitochondrial ATPase activity and had no effect on Ca^2 +-induced permeability transition. Morphine and Mor + Coc prevented lipid peroxidation, since in these conditions there was a decrease in O₂ consumption and in TBARS upon ADP/Fe^2 + stimulus, and a decrease in H₂O₂ formation, suggesting an antioxidant effect. Interestingly, heroin did not share morphine antioxidant properties.SignificanceOur results show that the sequential direct exposure of liver mitochondria to morphine and cocaine does not alter the effects observed in the presence of each drug alone.     

Design of a new fluorescent probe: Pyrrole/imidazole hairpin polyamides with pyrene conjugation at their γ-turn

Fluorophores that are conjugated with N-methylpyrrole-N-methylimidazole (Py–Im) polyamides postulates versatile applications in biological and physicochemical studies. Here, we show the design and synthesis of new types of pyrene-conjugated hairpin Py–Im polyamides (1–5). We evaluated the steady state fluorescence of the synthesized conjugates (1–5) in the presence and absence of oligodeoxynucleotides 5′-CGTATGGACTCGG-3′ (ODN 1) and 5′-CCGAGTCCATACG-3′ (ODN 2) and observed a distinct increase in emission at 386 nm with conjugates 4 and 5. Notably, conjugate 5 that contains a β-alanine linker had a stronger binding affinity (K_D = 1.73 × 10^?8 M) than that of conjugate 4 (K_D = 1.74 × 10^?6 M). Our data suggests that Py–Im polyamides containing pyrene fluorophore with a β-alanine linker at the γ-turn NH₂ position can be developed as the competent fluorescent DNA-binding probes.     

Fluoroquinolones stimulate the DNA cleavage activity of topoisomerase IV by promoting the binding of Mg2 + to the second metal binding site

BackgroundFluoroquinolones target bacterial type IIA topoisomerases, DNA gyrase and topoisomerase IV (Topo IV). Fluoroquinolones trap a topoisomerase–DNA covalent complex as a topoisomerase–fluoroquinolone–DNA ternary complex and ternary complex formation is critical for their cytotoxicity. A divalent metal ion is required for type IIA topoisomerase-catalyzed strand breakage and religation reactions. Recent studies have suggested that type IIA topoisomerases use two metal ions, one structural and one catalytic, to carry out the strand breakage reaction.MethodsWe conducted a series of DNA cleavage assays to examine the effects of fluoroquinolones and quinazolinediones on Mg^2 +-, Mn^2 +-, or Ca^2 +-supported DNA cleavage activity of Escherichia coli Topo IV.ResultsIn the absence of any drug, 20–30 mM Mg^2 + was required for the maximum levels of the DNA cleavage activity of Topo IV, whereas approximately 1 mM of either Mn^2 + or Ca^2 + was sufficient to support the maximum levels of the DNA cleavage activity of Topo IV. Fluoroquinolones promoted the Topo IV-catalyzed strand breakage reaction at low Mg^2 + concentrations where Topo IV alone could not efficiently cleave DNA.Conclusions and general significanceAt low Mg^2 + concentrations, fluoroquinolones may stimulate the Topo IV-catalyzed strand breakage reaction by promoting Mg^2 + binding to metal binding site B through the structural distortion in DNA. As Mg^2 + concentration increases, fluoroquinolones may inhibit the religation reaction by either stabilizing Mg^2 + at site B or inhibition the binding of Mg^2 + to site A. This study provides a molecular basis of how fluoroquinolones stimulate the Topo IV-catalyzed strand breakage reaction by modulating Mg^2 + binding.     

Post-translationally modified human lens crystallin fragments show aggregation in vitro

BackgroundCrystallin fragments are known to aggregate and cross-link that lead to cataract development. This study has been focused on determination of post-translational modifications (PTMs) of human lens crystallin fragments, and their aggregation properties.MethodsFour crystallin fragments-containing fractions (Fraction I [～3.5 kDa species], Fraction II [～3.5–7 kDa species], Fraction III [～7–10 kDa species] and Fraction IV [>10–18 kDa species]), and water soluble high molecular weight (WS-HMW) protein fraction were isolated from water soluble (WS) protein fraction of human lenses of 50–70 year old-donors. The crystallin fragments of the Fractions I–IV were separated by two-dimensional (2D)-gel electrophoresis followed by analysis of their gel-spots by mass spectrometry. The Fractions I–IV were examined for their molecular mass, particle-diameters, amyloid fibril formation, and for their aggregation by themselves and with WS-HMW proteins.ResultsCrystallin fragments in Fractions I–IV were derived from α-, β- and γ-crystallins, and their 2D-gel separated spots contained multiple crystallins with PTMs such as oxidation, deamidation, methylation and acetylation. Crystallin fragments from all the four fractions exhibited self-aggregated complexes ranging in M_r from 5.5×10⁵ to 1.0×10⁸ Da, with diameters of 10–28 nm, and amyloid fibril-like formation, and aggregation with WS-HMW proteins.ConclusionThe crystallin fragments exhibited several PTMs, and were capable of forming aggregated species by themselves and with WS-HMW proteins, suggesting their potential role in aggregation process during cataract development.General significanceCrystallin fragments play a major role in human cataract development.     

Cholesterol enrichment of rabbit platelets enhances the Ca2 + entry pathway induced by platelet-derived secondary feedback agonists

AimsHypersensitivity of platelets due to increased platelet cholesterol levels has been reported in hypercholesterolemia. However, the signaling pathways linking increased platelet reactivity and cholesterol contents are not fully understood. This study aims to determine the direct effect of cholesterol enrichment of platelets on the pathways including Ca^2 + mobilization and secondary feedback agonists such as adenosine diphosphate (ADP) and thromboxane A₂ (TXA₂).Main methodsIn vitro cholesterol enrichment of rabbit platelets was performed by incubation with cholesterol complexed with methyl-β-cyclodextrin. Ca^2 + mobilization was monitored using platelets loaded with fura-PE3/AM, a fluorescent calcium indicator. Released ATP and TXB₂ from platelets were measured by a luciferin–luciferase ATP assay system and a TXB₂ ELISA Kit, respectively.Key findingsCholesterol enrichment of rabbit platelets significantly enhanced Ca^2 + mobilization induced by thrombin, accompanying an augmented Ca^2 + entry. The augmentation of Ca^2 + entry by cholesterol enrichment was significantly suppressed by treatment with inhibitors for secondary feedback agonists. In cholesterol-enriched platelets, the amount of released ATP or TXB₂ induced by thrombin was not significantly altered in comparison with control platelets, whereas an increase in [Ca^2 +]_i induced by ADP or U46619, a TXA₂ mimetic, was significantly enhanced.SignificanceThese results suggest that cholesterol enrichment of rabbit platelets results in enhanced Ca^2 + mobilization via ADP/TXA₂-dependent augmentation of the Ca^2 + entry pathway. The results reveal a novel mechanism by which platelet hypersensitivity is regulated by cholesterol contents.     

Characteristics of activated carbon remove sulfur particles against smog

Sulfur particles, which could cause diseases, were the main powder of smog. And activated carbon had the very adsorption characteristics. Therefore, five sulfur particles were adsorbed by activated carbon and were analyzed by FT-IR. The optimal adsorption time were 120 min of Na₂SO₃, 120 min of Na₂S₂O₈, 120 min of Na₂SO₄, 120 min of Fe₂(SO₄)₃ and 120 min of S. FT-IR spectra showed that activated carbon had the eight characteristic absorption of SS stretch, H₂O stretch, OH stretch, CH stretch, conjugated CO stretch or CC stretch, CH₂ bend, CO stretch and acetylenic CH bend vibrations at 3850 cm^–1, 3740 cm^–1, 3430 cm^–1, 2920 cm^–1, 1630 cm^–1, 1390 cm^–1, 1110 cm^–1 and 600 cm^–1, respectively. For Na₂SO₃, the peaks at 2920 cm^–1, 1630 cm^–1, 1390 cm^–1 and 1110 cm^–1 achieved the maximum at 20 min. For Na₂S₂O₈, the peaks at 3850 cm^–1, 3740 cm^–1 and 2920 cm^–1 achieved the maximum at 60 min. The peaks at 1390 cm^–1, 1110 cm^–1 and 600 cm^–1 achieved the maximum at 40 min. For Na₂SO₄, the peaks at 3430 cm^–1, 2920 cm^–1, 1630 cm^–1, 1390 cm^–1, 1110 cm^–1 and 600 cm^–1 achieved the maximum at 60 min. For Fe₂(SO₄)₃, the peaks at 1390 cm^–1, 1110 cm^–1 and 600 cm^–1 achieved the maximum at 20 min. For S, the peaks at 1630 cm^–1, 1390 cm^–1 and 600 cm^–1 achieved the maximum at 120 min. It provided that activated carbon could remove sulfur particles from smog air to restrain many anaphylactic diseases.     

Structural and diffusion properties of formamide/water mixture interacting with TiO2 surface

The photoreaction and adsorption properties on surfaces, thermal decomposition, chemical transformation, and other properties of the formamide molecule are widely used to understand the origins of the formation of biological molecules (nucleosides, amino acids, DNA, monolayers, etc.) needed for life. The titanium oxide (TiO₂) surface can act both as a template on which the accumulation of adsorbed molecules like formamide occurs through the concentration effect, and as a catalytic material that lowers the activation energy needed for the formation of intermediate products. In this paper, a formamide–water solution interacting with TiO₂ (anatase) surface is simulated using the molecular dynamics method. The structural, diffusion and density properties of formamide–water mixture on TiO₂ are established for a wide temperature range from T = 250 K up to T = 400 K.     

Design,synthesis and structure–activity relationship of rhenium 2-arylbenzothiazoles as β-amyloid plaque binding agents

To continue our efforts toward the development of ^99mTc PiB analogs, we have synthesized 24 neutral and lipophilic Re (as a surrogate of ^99mTc) 2-arylbenzothiazoles, and explored their structure–activity relationship for binding to Aβ_1–40 fibrils. These Re complexes were designed and synthesized via the integrated approach, so their ^99mTc analogs would have a greater chance of crossing the blood–brain barrier. While the lipophilicities (log P_C18 = 1.59–3.53) of these Re 2-arylbenzothiazoles were all within suitable range, their binding affinities (K_i = 30–617 nM) to Aβ_1–40 fibrils varied widely depending on the selection and integration of the tetradentate chelator into the 2-phenylbenzothiazole pharmacophore. For potential clinical applications, further refinement to obtain Re 2-arylbenzothiazoles with better binding affinities (<10 nM) will likely be needed. The integrated approach reported here to generate compact, neutral and lipophilic Re 2-arylbenzothiazoles could be applied to other potent pharmacophores as well to convert other current Aβ PET tracers to their ^99mTc analogs for more widespread application via the use of SPECT scanners.     

Acylated iridoid glycosides and acylated rhamnopyranoses from Gmelina arborea flowers

Nine acylated iridoid glycosides (1–9), five acylated rhamnopyranoses (10–14) and verbascoside (15) were isolated from Gmelina arborea flowers, including 5 new compounds (1, 2, and 10–12). The cytoprotective activity of 11 selected compounds (1–8, 10, 11, and 15) against CCl₄-induced cytotoxicity on liver was determined. Compounds 1, 2, 4, 7, 8 and 15 displayed hepatoprotective activity. 6-O-α-l-(2″, 3″-di-O-trans-p-hydroxycinnamoyl)rhamnopyranosylcatalpol (2) exhibited the most potent cytoprotective effect with an EC₅₀ value of 42.5 μM (SI = 19.3) compared with biphenyldimethylesterate (DDB, EC₅₀ = 277.3 μM, SI = 9.8) and bicylo-ethanol (EC₅₀ = 279.2 μM, SI = 12.2). Among the acylated iridoid glycosides, the compounds (2 and 8) containing phenolic hydroxy groups were more active than were those lacking them.     

KMUP-1 ameliorates monocrotaline-induced pulmonary arterial hypertension through the modulation of Ca2+ sensitization and K+-channel

AimsThis study investigates the actions of KMUP-1 on RhoA/Rho-kinase (ROCK)-dependent Ca²⁺ sensitization and the K⁺-channel in chronic pulmonary arterial hypertension (PAH) rats.Main methodsSprague–Dawley rats were divided into control, monocrotaline (MCT), and MCT + KMUP-1 groups. PAH was induced by a single intraperitoneal injection (i.p.) of MCT (60 mg/kg). KMUP-1 (5 mg/kg, i.p.) was administered once daily for 21 days to prevent MCT-induced PAH. All rats were sacrificed on day 22.Key findingsMCT-induced increased right ventricular systolic pressure (RVSP) and right ventricular hypertrophy were prevented by KMUP-1. In myograph experiments, KCl (80 mM), phenylephrine (10 µM) and K⁺ channel inhibitors (TEA, 10 mM; paxilline, 10 µM; 4-AP, 5 mM) induced weak PA contractions in MCT-treated rats compared to controls, but the PA reactivity was restored in MCT + KMUP-1-treated rats. By contrast, in β-escin- or α-toxin-permeabilized PAs, CaCl₂-induced (1.25 mM, pCa 5.1) contractions were stronger in MCT-treated rats, and this action was suppressed in MCT + KMUP-1-treated rats. PA relaxation in response to the ROCK inhibitor Y27632 (0.1 μM) was much higher in MCT-treated rats than in control rats. In Western blot analysis, the expression of Ca²⁺-activated K⁺ (BK_Ca) and voltage-gated K⁺ channels (Kv2.1 and Kv1.5), and ROCK II proteins was elevated in MCT-treated rats and suppressed in MCT + KMUP-1-treated rats. We suggest that MCT-treated rats upregulate K⁺-channel proteins to adapt to chronic PAH.SignificanceKMUP-1 protects against PAH and restores PA vessel tone in MCT-treated rats, attributed to alteration of Ca²⁺ sensitivity and K⁺-channel function.     

Effect of phytic acid,tannic acid and pectin on fasting iron bioavailability both in the presence and absence of calcium

ObjectiveTo determine the effect of phytic acid, tannic acid and pectin on fasting non-heme iron bioavailability in both the presence and absence of calcium.Research methodsTwenty-eight apparently healthy adult females participated in two iron absorption studies using radioactive iron isotopes (⁵⁹Fe and ⁵⁵Fe). One group received 5 mg of iron (as FeSO₄) alone (control), together with 10 mg of phytic acid, 100 mg of tannic acid and 250 mg of pectin (study A), on different days. The second group received the same iron doses and compounds as the other group, plus 800 mg of calcium (CaCl₂) (study B). The compounds were administered after an overnight fast, and no food or beverages were consumed for the following 3 h. Iron status and circulating radioactivity were measured in venous blood samples.ResultsThe geometric means of iron bioavailability (range ± 1SD) for iron alone, iron with phytic acid, iron with tannic acid, and iron with citrus pectin were 25.0% (11.9–52.0); 18.9% (9.9–35.8); 16.8% (8.7–32.3); and 21.1% (10.2–43.9), respectively (repeated-measures ANOVA, p < 0.02 (Dunnett's post hoc: control vs tannic acid p < 0.05). When 800 mg of calcium was added (study B), iron bioavailability was 16.7% (10.1–27.5); 13.2% (7.1–24.6); 14.8% (8.8–25.1); and 12.6% (5.5–28.8), respectively (repeated-measures ANOVA, NS).ConclusionsTannic acid decreases the fasting bioavailability of non-heme iron, however this effect did not exist in the presence of calcium. No effect was observed by phytic acid or citrus pectin on fasting non-heme iron bioavailability in both the presence and absence of calcium.     

Effect of ligand congeniality on energy transfer reaction between photo-excited tris(bipyridine)ruthenium(II) and chromate(III) complexes in aqueous solutions

Energy-transfer rate-constants from photo-excited [Ru(N–N)₃]²⁺ (N–N = 2,2′-bipyridine (bpy), 4,4′-dimethyl-2,2′-bipyridine (4dmb), 5,5′-dimethyl-2,2′-bipyridine (5dmb)) to [Cr(O–O)₃]³⁻ (O–O²⁻ = ox²⁻ ((COO⁻)₂), mal²⁻ (CH₂(COO⁻)₂)) and [Cr(CN)₆]³⁻ in encounter complexes were evaluated in aqueous solutions containing alkali metal ion. The rate constant depends on the molecular size of the ruthenium(II) complex: 1.8 × 10⁸ s⁻¹ for [Ru(bpy)₃]²⁺ (molecular radius, r = 5.8 Å), 1.4 × 10⁸ s⁻¹ for [Ru(5dmb)₃]²⁺ (r = 6.1 Å) and 0.96 × 10⁸ s⁻¹ for [Ru(4dmb)₃]²⁺ (r = 6.7 Å) in the system of [Ru(N–N)₃]²⁺–[Cr(ox)₃]³⁻ in aqueous solution. However, the rate constant is much more sensitive to the chromate(III) complex than to ruthenium(II) complex; 1.8 × 10⁸ s⁻¹ and 0.43 × 10⁸ s⁻¹ for [Cr(ox)₃]³⁻ (r = 4.0 Å) and [Cr(mal)₃]³⁻ (r = 4.2 Å) in the [Ru(bpy)₃]²⁺–[Cr(O–O)₃]³⁻ systems, respectively. We conclude that the congeniality between the donor’s and acceptor’s ligands in encounter complex plays an important role in energy transfer in aqueous solution.     

Acute and chronic nitrite toxicity in juvenile pike-perch (Sander lucioperca) and its compensation by chloride

Pike-perch Sander lucioperca is currently considered as one of the most promising candidates for production in freshwater recirculation aquaculture systems (RAS). Here, due to the lack of studies on nitrite (NO₂^?) toxicity in pike-perch, a flow-through exposure at 0, 0.44, 0.88, 1.75, 3.5, 7, 14 and 28 mg/L NO₂^?–N was carried out to determine the acute and chronic toxicity over a period of 32 days. In juvenile pike-perch, 120 h LC₅₀ was 6.1 mg/L NO₂^?–N and at ≥ 14 mg/L NO₂^?–N all fish had died within 24 h. Chronic exposure revealed a significant build up of NO₂^? in the plasma as well as in the muscles at ≥ 0.44 mg/L NO₂^?–N peaking in fish exposed to the highest concentration of 3.5 mg/L NO₂^?–N after 32 days. Still, due to high individual variation methemoglobin (MetHb) was only significantly increased (p < 0.01) at 3.5 mg/L NO₂^?–N. No adverse effects on red blood cells (RBC) and hematocrit were observed in any of the treatments. In a second experiment, compensation of NO₂^? toxicity at increasing chloride concentrations (40 (freshwater), 65, 90, 140, 240, 440 mg/L Cl^?) was observed at a constant exposure of 10 mg/L NO₂^?–N for 42 days. At ≥ 240 mg/L Cl^?, NO₂^? build-up in blood plasma and muscle was completely inhibited. At lower Cl^? concentrations (≤ 140 mg/L), NO₂^? was significantly increased in plasma, but only insignificantly elevated in muscle due to high individual variation. MetHb was increased significantly difference only at 40 mg/L Cl^? (freshwater control) compared to the control. Again, high individual variations were observed. As a conclusion, S. lucioperca is moderately sensitive towards NO₂^? and acceptable levels in RAS should hence not exceed 1.75 mg/L NO₂^?–N to avoid MetHb formation. However, based on the 120 h LC₅₀ and a factor of 0.01 according to Sprague (1971), a NO₂^? concentration of ≤ 0.061 mg/L NO₂^?–N is considered as “safe.” Thereby, no NO₂^? should accumulate in the plasma or muscle tissue during chronic exposure. For 10 mg/L NO₂^?–N, ≥ 240 mg/L chloride compensates for NO₂^? uptake in plasma and muscle.     

TEP/TDM 18F-choline dans les récidives biologiques des cancers de la prostate traites par radiothérapie externe ou curiethérapie : impact du PSA et de sa cinétique

AimTo determine the impact of PSA and its kinetics on ¹⁸F-Choline PET/CT (FCH PET) ability to detect site of relapse in prostate cancer initially treated with external beam radiotherapy (EBRT) or brachytherapy (IBT).MethodsWe retrospectively enrolled PET FCH performed for suspicion of biochemical relapse after EBRT/IBT from January 2010 to January 2017 at Institut Curie. PSA_trigger, ΔPSA_nadir (PSA_trigger-PSA_nadir), PSA doubling time (PSA_dt) and velocity (PSA_vel) were compared between positive and negative results. Logistic regression analysis was used to determine the relationship between these parameters and PET ability to detect True Positives (TP).ResultsIn all, 271 FCH PET met the inclusion criteria: 169 after treatment with EBRT and 102 after IBT. Positivity rate was 67.9%, and 63.4% of TP were local relapses. Overall sensitivity and specificity were 81.2% and 71.0%. PSA_trigger was 3.32 ng/mL (interquartile space: IQS 2.28–5.77) when PET was negative and 5.15 ng/mL (IQS 3.16–10.17) when positive, ΔPSAnadir was respectively 2.76 ng/mL (IQS 1.84–4.69) and 4.57 ng/mL (IQS 2.48–8.85), PSA_dt 10.78 months (IQS 5.46–20.07) and 7.23 months (EI 2.58–14.14), and PSA_vel 2.16 ng/mL/year (EI 1.02–4.80) et 4.92 ng/mL/year (1.89–16.02) (P < 0.001). Positivity rate increased with PSA_trigger and ΔPSA_nadir. We found PSA_dt ≤ 9 months (P = 0.029; OR = 2.97, IC_95% [1.12–7.88]) and ΔPSA_nadir ≥ 3 ng/mL (P = 0.03; OR = 2.56, IC_95% [1.37–4.77]) to be independent predictive factors of PET sensitivity.ConclusionDetection of relapse after EBRT or IBT with PET FCH is influenced by PSA and its kinetics. In our study, PSA_dt and ΔPSA_nadir were independant predictors of PET performance, but initial treatment and tumor characteristics were not.     

Nanostructured materials for magnetic biosensing

BackgroundMagnetic nanoparticles (MNPs) are at the leading edge of the field of biomedical applications and magnetic biosensing.MethodsMNPs were fabricated by electrophysical methods of the laser target evaporation (LTE) and spark discharge with electrodynamic acceleration of plasma jumpers (SD). Synthesis of polyacrylamide hydrogel was done in the presence of Fe₂O₃ MNPs in different concentrations obtained by LTE. [FeNi/Ti]₃/Cu/[Ti/FeNi]₃/Ti multilayers for giant magnetoimpedance (GMI) based sensitive elements were prepared by rf-sputtering for testing a biosensor prototype.ResultsIron oxide MNPs, ferrofluids, ferrofluids contacting with biological systems, synthetic ferrogels mimicking natural tissues – are the steps of the discussed in this work development of bionanomaterials. Thorough the structural and magnetic studies of a multilayered sensitive element, MNPs and ferrogels insure the complete characterization of biosensor prototype. The GMI responses were carefully evaluated in initial state and in the presence of ferrogel with known concentration of MNPs. SD MNPs had the smallest 5–8 nm size. This nanomaterial was characterized by large internal strains of the order of 25 × 10^− 3, which can play an important role for the interaction with different biosystems.ConclusionsIron oxide MNPs were fabricated by LTE and SD methods. SD MNPs had the smallest 5–8 nm size and large internal strains of the order of 25 × 10^− 3. Designed GMI biosensor prototype allowed precise evaluation of the stray field of the MNPs present in the ferrogel by evaluating the systematic changes of the GMI in a 20–400 MHz frequency range.General significanceThis work summarizes recent developments in the field of nanomaterials potentially applicable in magnetic biosensing.