Tuning the reaction products of ruthenium and ciprofloxacin for studies of DNA interactions

This work presents two potential metallo-drugs, the ionic (C17H19FN3O3)(3)[RuCl6]center dot 3H(2)O (1) and the coordination [Ru(C17H17FN3O3)(3)]center dot 4H(2)O (2) compounds, obtained by the combination of ruthenium(III) and ciprofloxacin in different synthetic conditions. The ESI MS spectrum of 1 displayed a main peak at m/z = 994.6, assigned to the gaseous phase adduct (ciprofloxacin)(3)center dot H+, while 2 featured peaks at m/z 1093.3 and 547.1 ascribed to [Ru(C17H17FN3O3)(3)center dot H+-4H(2)O](+) and [Ru(C17H17FN3O3)(3)center dot 2H(+)-4H(2)O](2+). Thermal analysis corroborated the proposed water content for both complexes. Absorption spectra of the compounds in aqueous medium are dominated by ciprofloxacin transitions in the UV region but displayed weak bands in the visible region, assigned to ligand field transitions. The cyclic voltammograms of 2 exhibited a quasi-reversible process ascribed to the Ru(II)/(III) redox pair at -0.25V (vs. SHE) while 1 displayed this process at -0.11 V, showing that the central ruthenium ion is stabilized in the (III) oxidation state by the coordination to the hard oxygen atoms of ciprofloxacin. The solubility of 1 is pH dependent (as well as free ciprofloxacin) while 2 is fully water soluble and stable under physiological pH for at least 48 h. The compounds are also stable under incubation conditions (stomach pH and 37 degrees C) without significant pH lowering. An interaction study of 2 with ct-DNA showed a value of K-b = 2.47 (+/- 0.89) x 10(4) mol(-1) L for the intrinsic binding constant.

Constraining the dark energy and smoothness parameter with type Ia supernovae and gamma-ray bursts

The existence of inhomogeneities in the observed Universe modifies the distance-redshift relations thereby affecting the results of cosmological tests in comparison to the ones derived assuming spatially uniform models. By modeling the inhomogeneities through a Zeldovich-Kantowski-Dyer-Roeder approach which is phenomenologically characterized by a smoothness parameter alpha, we rediscuss the constraints on the cosmic parameters based on type Ia supernovae (SNe Ia) and gamma-ray bursts (GRBs) data. The present analysis is restricted to a flat Lambda CDM model with the reasonable assumption that Lambda does not clump. A chi(2) analysis using 557 SNe Ia data from the Union2 compilation data (R. Amanullah et al., Astrophys. J. 716, 712 (2010).) constrains the pair of parameters (Omega(m), alpha) to Omega(m) = 0.27(-0.03)(+0.08) (2 sigma) and alpha >= 0.25. A similar analysis based only on 59 Hymnium GRBs (H. Wei, J. Cosmol. Astropart. Phys. 08 (2010) 020.) constrains the matter density parameter to be Omega(m) = 0.35(-0.24)(+0.62) (2 sigma) while all values for the smoothness parameter are allowed. By performing a joint analysis, it is found that Omega(m) = 0.27(-0.06)(+0.06) and alpha >= 0.52. As a general result, although considering that current GRB data alone cannot constrain the smoothness alpha parameter, our analysis provides an interesting cosmological probe for dark energy even in the presence of inhomogeneities.

Fine-tuning of defensive behaviors in the dorsal periaqueductal gray by atypical neurotransmitters

This paper presents an up-to-date review of the evidence indicating that atypical neurotransmitters such as nitric oxide (NO) and endocannabinoids (eCBs) play an important role in the regulation of aversive responses in the periaqueductal gray (PAG). Among the results supporting this role, several studies have shown that inhibitors of neuronal NO synthase or cannabinoid receptor type 1 (CB1) receptor agonists cause clear anxiolytic responses when injected into this region. The nitrergic and eCB systems can regulate the activity of classical neurotransmitters such as glutamate and γ-aminobutyric acid (GABA) that control PAG activity. We propose that they exert a ‘fine-tuning’ regulatory control of defensive responses in this area. This control, however, is probably complex, which may explain the usually bell-shaped dose-response curves observed with drugs that act on NO- or CB1-mediated neurotransmission. Even if the mechanisms responsible for this complex interaction are still poorly understood, they are beginning to be recognized. For example, activation of transient receptor potential vanilloid type-1 channel (TRPV1) receptors by anandamide seems to counteract the anxiolytic effects induced by CB1 receptor activation caused by this compound. Further studies, however, are needed to identify other mechanisms responsible for this fine-tuning effect.

Comparison of physical properties of two exogenous surfactants: new parameter.

The pulmonary surfactant has essential physical properties for normal lung function. The most important property is the surface tension. In this work, it was evaluated the surface tension of two commercial exogenous surfactants used in surfactant replacement therapy, poractant alfa (Curosurf, Chiesi Farmaceuticals, Italy) and beractant (Survanta, Abbott Laboratories, USA) using new parameters. A Langmuir film balance (Minitrough, KSV Instruments, Finland) was used to measure surface tension of poractant alfa and beractant samples. For both samples, we prepared a solution of 1 mg/m dissolved in chloroform (100π`), which was applied over a subphase of milli-Q water (175 ml) in the chamber of the balance. The chamber has two moving barriers that can change its surface area between a maximal value of 112.5 cm 2 , and a minimal value of 22.5 cm 2, defining a balance cycle. Each surfactant had its surface tension evaluated during 20 balance cycles for three times. Four quantities were calculated from the experiment: Minimum Surface Tension (MTS), defined as the surface tension at minimal surface area during the first cycle; Mean Work Cycle (MWC), defined as the mean hysteresis area of the measured surface tension curve of the last 16 balance cycles; Critical Active Surface Area in Compression (CASAC) or in Expansion (CASAE), defined as the maximal chamber area where the surfactant is active on the surface in compression or expansion. The t-test was applied to verify for statistical significance of the results. Comproved with the MST is the same reported in literature, the differences between MWC, CASAC, and CASAE were statistically significant (p<0.001). The MWC, CASAC and CASAE were higher for poractant alfa than for beractant. A higher MWC for poractant alfa means higher elastic recoil of the lung in comparison with beractant. Using a different methodology, our results showed that poractant alfa is probably more effective in a surfactant replacement therapy than beractant due the use of poractant alfa in relation to the use of beractant in preterm infants with Respiratory Distress Syndrome (RDS).