Raised corticosterone in the rat after exposure to the elevated plus-maze

Rats given one or two 5-min trials in the elevated plus-maze had plasma corticosterone concentrations significantly higher than the home cage control group and there was no sign of habituation in the group given two trials. In rats given two plus-maze trials the corticosterone responses were significantly higher in the group given 10-min rather than 5-min trials. A previous experience of cat odour (1 week earlier) has no effect on the plasma corticosterone response, but did have an anxiogenic effect that could be detected by a decrease in the percentage of time spent on the open arms of the plus-maze. The results are discussed with reference to the nature of anxiety generated by trials 1 and 2 and by the trial duration in the plus-maze, and with respect to dissociation between behavioural and endocrinological measures.     

Abscess formation after transobturator sling placement: a case report

New techniques of sling placement may be associated with infectious complications. Slings through the obturator foramen and thigh can lead to a significant abscess formation within the thigh adductor muscles. A large thigh abscess associated with a transobturator sling was diagnosed and treated. The authors report the evaluation and treatment of a unique infectious complication of transobturator slings.     

Three-year outcomes from the CRADLE study in de novo pediatric kidney transplant recipients receiving everolimus with reduced tacrolimus and early steroid withdrawal

CRADLE was a 36-month multicenter study in pediatric (≥1 to <18 years) kidney transplant recipients randomized at 4 to 6 weeks posttransplant to receive everolimus + reduced-exposure tacrolimus (EVR + rTAC; n = 52) with corticosteroid withdrawal at 6-month posttransplant or continue mycophenolate mofetil + standard-exposure TAC (MMF + sTAC; n = 54) with corticosteroids. The incidence of composite efficacy failure (biopsy-proven acute rejection [BPAR], graft loss, or death) at month 36 was 9.8% vs 9.6% (difference: 0.2%; 80% confidence interval: −7.3 to 7.7) for EVR + rTAC and MMF + sTAC, respectively, which was driven by BPARs. Graft loss was low (2.1% vs 3.8%) with no deaths. Mean estimated glomerular filtration rate at month 36 was comparable between groups (68.1 vs 67.3 mL/min/1.73 m²). Mean changes (z-score) in height (0.72 vs 0.39; P = .158) and weight (0.61 vs 0.82; P = .453) from randomization to month 36 were comparable, whereas growth in prepubertal patients on EVR + rTAC was better (P = .050) vs MMF + sTAC. The overall incidence of adverse events (AEs) and serious AEs was comparable between groups. Rejection was the leading AE for study drug discontinuation in the EVR + rTAC group. In conclusion, though AE-related study drug discontinuation was higher, an EVR + rTAC regimen represents an alternative treatment option that enables withdrawal of steroids as well as reduction of CNIs for pediatric kidney transplant recipients. ClinicalTrials.gov: NCT01544491.     

“One-trial tolerance” to the anxiolytic actions of benzodiazepines in the elevated plus-maze,or the development of a phobic state?

Diazepam (5 mg/kg) increased the number of shocks accepted by rats on two successive trials in the punished drinking test. Thus, the phenomenon of one trial tolerance to the anxiolytic effects of benzodiazepines in the elevated plus-maze does not generalise to this other animal test of anxiety. FG 7142 (20 mg/kg) and prior exposure to the odour of a cat had significant anxiogenic effects on two successive trials in the plus-maze. Thus the phenomenon of one trial tolerance does not generalise to these anxiogenic effects in the plus-maze. Furthermore, chlordiazepoxide retained its ability to counteract the anxiogenic effects in the plus-maze of prior exposure to cat odour, over successive trials. On the basis of these and previous experiments it is suggested that the state of anxiety generated on trial 2 in the plus-maze is close to a phobic state, against which benzodiazepines are relatively ineffective. Chlordiazepoxide (5 and 10 mg/kg) was also ineffective against the behavioural responses of rats during exposure to cat odour, another possible animal test of phobia. This contrasted with its efficacy against the anxiogenic effects of cat odour that subsequently generalised to and could be detected in the plus-maze.     

Performance of a Rapid Self-Test for Detection of Trichomonas vaginalis in South Africa and Brazil

Women participating in studies in Brazil (n = 695) and South Africa (n = 230) performed rapid point-of-care tests for Trichomonas vaginalis on self-collected vaginal swabs. Using PCR as the gold standard, rapid self-testing achieved high specificity (99.1%; 95% confidence interval [CI], 98.2 to 99.6%) and moderate sensitivity (76.7%; 95% CI, 61.4 to 88.2%). These tests may be considered an alternative to syndromic management in resource-poor settings.     

Peroxoniobium inhibits leukemia cell growth

A new class of polyoxoniobate complex has been synthesized and characterized as a novel anticancer agent for photodynamic therapy. The complex inhibits the growth of chronic myelogenous leukemia cells with an IC₅₀ value of 30 μM, in the dark. However, upon exposure to light (365 nm) there is a fivefold increase in the cytotoxic activity. Light radiation activate the complex with the formation of radical species capable of interacting with DNA according to our experimental and theoretical data.

A new class of polyoxoniobate complex has been synthesized and characterized as a novel anticancer agent for photodynamic therapy.

In this work, we prepared a photosensitive peroxoniobium complex presenting a balance with an active radical phase when illuminated with radiation of 365 nm. A versatile niobium species of amorphous structure was obtained by the reaction of niobium ammonium oxalate with ammonium hydroxide up to pH 7. The material obtained, a niobium oxyhydroxide (NbO₂(OH)) (white solid),^1,2 can be modified with the generation of NbO₂(OH)O₂˙⁻ peroxo groups (yellow solid).³ The yellow compound is formed by treatment with H₂O₂. The absorption radiation in the visible region due to the charge transfer transition between the peroxo group and the niobium is shown in Fig. 1.Open in a separate windowFig. 1UV-Vis profile of the catalysts.This complex with the radical as an intermediate is favored in the presence of visible and UV radiation. This property is of interest for photodynamic therapy of cancer (PDT), which involves the exposure of malignant cells containing a photosensitizer molecule to light irradiation, in the presence of oxygen species. The photoactivated drug produces reactive oxygen species that initiate a series of events, resulting in cell death. Selective light activation allows a preferential tumor destruction in comparison to healthy tissues.⁴ Several metal complexes exhibit photocytotoxicity under UV or visible light,^5,6 but data about niobium compounds are very scarce in the literature.⁷The polyoxoniobate, generated from niobium oxyhydroxide described here can be very active in the treatment of diseased cells when illuminated with visible or UV radiation due to its light absorption capacity because of the peroxo groups formed. The peroxoniobium complex has some advantages, such as ease synthesis and in mild conditions, high solubility, low activity under light off, and resistance to inactivation by thiol reagents. Moreover, it is nontoxic⁸ and does not employ noble metals like most of the compounds proposed in the literature. Actually, niobium oxide was tested as a bone implant component and showed absence of inflammatory cells or degeneration of the osteoblasts without any sign of damage to the preexisting bone tissue, showing compatibility with the bone tissue.^9–11The innovative part in the process of obtaining the polyoxoniobate complex presented in this work consists in the leaching of the complex when treating the niobium oxyhydroxide with H₂O₂. With the treatment, a yellow solid and a leached yellow liquid is obtained, which is the complex containing peroxoniobium in its structure, sensitive to the UV-Vis radiation generating radical species. This species generated with the leaching at neutral pH presents high negative charge and a kinetic volume of 223 nm. The XRD of the lyophilized polyoxoniobate indicated strong amorphous character. However, the polyoxoniobate is known to form well defined polyoxometalates such as Lindqvist ([Nb₆O₁₉]⁸⁻) and decaniobate ([Nb₁₀O₂₈]⁶⁻). Fig. 2 shows a comparison between the experimental and PBE/LANL2DZ/aug-cc-pVDZ DFT IR spectra. It is clear that the pattern of the decaniobate structure is closer to the experimental spectrum. One should keep in mind that DFT frequencies are normally 10% underestimated with respect to the experimental values. The broader absorption below 600 cm⁻¹ can be attributed to the interaction between different decaniobate structures forming the amorphous solid. The calculated peaks at 710, 760 and 860 cm⁻¹ are related to the experimental peaks of 800, 870 and 910 cm⁻¹ indicating that decaniobate is the local arrangement of the polyoxoniobate complex.Open in a separate windowFig. 2Infrared spectra for experimental procedures, Lindqvist and decaniobate structures (simulated). The line shape chosen was Lorentzian and the half-width is about 20.The generation of reactive oxygen under radiation was confirmed by the reaction of the complex with an organic dye, which was monitored by UV-Vis spectroscopy (Fig. 3). The spectrum of the dye solution shows the characteristic peak of the methylene blue (MB) at 663 nm (black trace). It can be clearly seen that in the presence of the peroxoniobium complex and radiation (365 nm) the signal decreased indicating the reaction of the peroxoniobium complex with the dye (blue trace). In the absence of light, there is no decrease in the signal related to the dye, indicating the need of the radiation to activate the oxidation action of the peroxoniobium complex. The equilibrium in which the radical species forms it is not necessary to use a photosensitizer agent, such as porphyrins.⁴ A further investigation was carried out by ³¹P NMR (Fig. S1^†) using guanosine as model molecule able to react with the peroxoniobium complex. The ³¹P NMR spectrum shown in Fig. S1-a^† corresponds to 5-GMP and revealed that the phosphorus atom in the structure exhibits a chemical shift at δ 5.93. When 5-GMP and the polyoxoniobate are in contact, no significant changes are observed in the ³¹P spectrum, only a small displacement of the phosphorus signal to δ 5.90 (Fig. S1-b^†). However, when the 5-GMP and polyoxoniobate mixture is submitted to radiation (Fig. S1-c^†), an interaction between the compounds occurs, giving rise to a new species that presents a different chemical shift in the P spectrum (δ 5.27).Open in a separate windowFig. 3UV-Vis profile of the reaction of the Nb complex with the organic dye (10 mg L⁻¹).The effect of the peroxoniobium on the growth of K562 cells was evaluated after 4 h of incubation. The compound inhibits K562 cell growth in a concentration-dependent manner, with an IC₅₀ of 30.0 ± 1.5 μmol L⁻¹. Ammonium niobate(v) oxalate was also tested and it has no effect on K562 cells up to 100 μM. The cytotoxic activity of polyoxoniobate increases by 5 times upon 5 min of UV-A light irradiation, with an IC₅₀ value of 6.2 ± 0.4 μmol L⁻¹ (Fig. 4). The higher activity, when exposed to light, associated to the low toxicity of niobium compounds place the peroxoniobium complex as a candidate for photodynamic therapy.Open in a separate windowFig. 4Photocytotoxic effect of the peroxoniobium complex. K562 cells were incubated for 4 h in the presence of different complex concentrations, in the dark (black bars) and after 5 min of UV-A light exposure (red bars). The values are the average of three independent experiments.There are few reports in the literature about the cytotoxic activity of niobium compounds. A peroxo niobium complex with ascorbic acid (K₃[Nb(Asc)(O₂)₃]) is moderately active in HL60 human leukemia cells but not in K562 human myelogenous leukemia cells.¹² A tetrameric Nb28-containing cluster inhibits the growth of the human breast cancer MCF-7 cells line with an IC₅₀ value of 5.21, after 48 h of incubation.¹³Methylene blue (MB) is one of the main photosensitizing agents used in PDT due to its good tissue penetration and low cytotoxicity.¹⁴ It is active in several types of tumors upon irradiation with red laser light.¹⁵ This fact allied to the ability of the peroxoniobium compound to interact with MB (Fig. 3) prompted us to investigate its effect in the MB photocytotoxicity. We have first checked that exposure to UV-A light did not affect the cytotoxicity of MB in K562 cells (

Telavancin In Vitro Activity against a Collection of Methicillin-Resistant Staphylococcus aureus Isolates,Including Resistant Subsets,from the United States

Telavancin had MIC₅₀, MIC₉₀, and MIC₁₀₀ values of 0.03, 0.06, and 0.12 μg/ml, respectively, against methicillin-susceptible Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), and non-multidrug-resistant (non-MDR) and MDR subsets. MRSA with elevated MIC values for vancomycin (2 to 4 μg/ml) or daptomycin (1 to 2 μg/ml) had telavancin MIC₅₀ (0.06 μg/ml) values 2-fold higher than those of isolates with lower MIC results (MIC₅₀, 0.03 μg/ml). However, telavancin had MIC₉₀ and MIC₁₀₀ results of 0.06 and 0.12 μg/ml (100% susceptible), respectively, regardless of the MRSA subset.     

SR141716A-sensitive enhancement of ET-1 hypotensive effect by chronic NOS inhibition

The present study evaluated the potential mechanism involved in the hypotensive effect induced by ET-1 in rats treated with the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) in the drinking water during 7 days. Hypertension developed in the L-NAME-treated rats (164+/-3 versus 112+/-1 mm Hg in untreated control rats), and the hypotensive effect of ET-1 (100 pmol/kg IV) was significantly enhanced compared with control rats (32+/-2% versus 20+/-1% fall in mean arterial pressure). The enhanced ET-1 hypotensive effect in L-NAME-treated rats was abolished by the ETB receptor antagonist BQ-788 but was unaltered by the cyclooxygenase inhibitor diclofenac, the cytochrome P450 inhibitor fluconazole, or the potassium channel blockers apamin, glibenclamide, tetraethylammonium, and 4-aminopyridine. Pretreatment with the cannabinoid CB1 receptor antagonist SR141716A significantly reduced the hypotensive response to ET-1 in L-NAME-treated rats (20+/-1%), although it did not modify the response in untreated control rats (17+/-1%). These findings indicate that in rats under chronic NOS inhibition, the hypotensive effect of ET-1 is unexpectedly enhanced and appears to be mediated by a non-NO/non-prostanoid mechanism and involves an SR141716A-sensitive mechanism triggered by ETB receptor activation.