Antitrypanosomal action of cis-diamminedichloroplatinum (II) analogs

The present report deals with the alterations produced by cis-diamminedichloroplatinum (II) (DDP), and 2 of its analogs: cis-Pt(II)(tranylcypromine)2Cl2 and cis-Pt(II)(benzothiazole)2Cl2 in cultured epimastigote forms of Trypanosoma cruzi. Studies have been performed at the ultrastructural level and the inhibitory effect of these complexes on macromolecule synthesis, evaluated by 3H-thymidine, 3H-uridine, and 3H-leucine incorporation, has been investigated. DDP at concentrations of 50 and 100 micrograms/ml does not inhibit significantly the incorporation of radioactive precursors, but a clear decrease was observed with the 2 analogs. Eight hours of treatment at a concentration of 10 micrograms/ml rendered in all 3 cases an increase in autophagic vacuoles and lipids as well as an abnormal condensation of the nucleus chromatin.     

Effect of rhodium (III) complex on experimental carcinogenesis in the livers of rats treated with thioacetamide

Enzyme activities and protein content were determined in the cytosolic and mitochondrial fractions of liver homogenates obtained from Rh(III) complex-, thioacetamide- and thioacetamide + Rh(III) complex-treated rats. The Rh(III) complex administered to nonthioacetamide-treated rats produced no significant changes either in the enzymatic activities assayed or in the protein concentration. The Rh(III) complex administered to thioacetamide-treated rats produced significant restoration of the following altered values: cytosolic and mitochondrial aspartate aminotransferase, glutamate dehydrogenase, NADP-isocitrate dehydrogenase, and protein concentration. However, a further increase was produced in the activities of glucose-6-phosphate dehydrogenase and malic enzyme. These increases can be interpreted in terms of an enhancement of the NADPH-dependent detoxifying processes and of nucleic acid synthesis and repair.     

Molecular dipole effects on tuning electron transfer in a porphine–quinone complex: a DFT and TDDFT study

The effect of a strong electric field generated by molecular dipoles on the ground state electronic structure and the Q and B states as well as the lowest charge transfer (CT) excited state of porphine–2,5-dimethyl-1,4-benzoquinone (PQ) complex has been investigated theoretically. Density functional theory DFT and time-dependent DFT (TDDFT) with the BH&HLYP hybrid functional have been applied in these calculations. The molecular dipole effect was generated by imposing one or two helical homopeptides consisting of eight α-aminoisobutyric acid residues (Aib₈) close to the PQ complex. The molecular dipoles in a close proximity to the PQ complex expose it to an electric field of the order of magnitude of 10⁹ V/m. The presence of the ambient molecular dipoles affects mainly the energy of the lowest CT state and barely the energies of the Q and B states. The molecular dipoles affect the energies of the excited states in a similar way as an external electrostatic field. Hence, the electric field induced by the molecular dipoles of the helical peptides could be used analogously to the external electrostatic field to control electron transfer (ET) in the PQ complex.     

Stress-Induced Visceral Hypersensitivity in Maternally Separated Rats Can Be Reversed by Peripherally Restricted Histamine-1-Receptor Antagonists

Background

The histamine-1 receptor (H1R) antagonist ketotifen increased the threshold of discomfort in hypersensitive IBS patients. The use of peripherally restricted and more selective H1R antagonists may further improve treatment possibilities. We examined the use of fexofenadine and ebastine to reverse post-stress visceral hypersensitivity in maternally separated rats.

Methods

The visceromotor response to colonic distension was assessed in adult maternally separated and nonhandled rats pre- and 24 hours post water avoidance. Subsequently rats were treated with vehicle alone or different dosages of fexofenadine (1.8 and 18 mg/kg) or ebastine (0.1 and 1.0 mg/kg) and re-evaluated. Colonic tissue was collected to assess relative RMCP-2 and occludin expression levels by Western blot and histamine-1 receptor by RT-qPCR. β-hexosaminidase release by RBL-2H3 cells was used to establish possible mast cell stabilizing properties of the antagonists.

Key results

Water avoidance only induced enhanced response to distension in maternally separated rats. This response was reversed by 1.8 and 18 mg/kg fexofenadine. Reversal was also obtained by 1.0 but not 0.1 mg/kg ebastine. RMCP-2 expression levels were comparable in these two ebastine treatment groups but occludin was significantly higher in 1.0 mg/kg treated rats. There were no differences in histamine-1 receptor expression between nonhandled and maternally separated rats. Fexofenadine but not ebastine showed mast cell stabilizing quality.

Conclusions

Our results indicate that the peripherally restricted 2^nd generation H1-receptor antagonists fexofenadine and ebastine are capable of reversing post stress visceral hypersensitivity in rat. These data justify future IBS patient trials with these well tolerated compounds.     

Regulation of PSII function in Cyanothece sp. ATCC 51142 during a light–dark cycle

Photosynthesis Research - Cyanobacteria, as well as green algae and higher plants, have highly conserved photosynthetic machinery. Cyanothece sp. ATCC 51142 is a unicellular, aerobic, diazotrophic...     

Remodeling of resistance arteries in organoid culture is modulated by pressure and pressure pulsation and depends on vasomotion

The hypothesis was tested that pressure and pressure pulsation modulate vascular remodeling. Arterioles ( approximately 200 microm lumen diameter) were dissected from rat cremaster muscle and studied in organoid culture. In the first series, arterioles were kept at a stable pressure level of either 50 or 100 mmHg for 3 days. Both groups showed a progressive increase in myogenic tone during the experiment. Arterioles kept at 50 mmHg showed larger endothelium-dependent dilation, compared with vessels kept at 100 mmHg on day 3. Remodeling, as indicated by the reduction in maximally dilated diameter at 100 mmHg, was larger in arterioles kept at 50 mmHg compared with 100 mmHg: 34 +/- 4.5 versus 10 +/- 4.8 microm (P < 0.05). In the second series, arterioles were subjected to a stable pressure of 60 mmHg or oscillating pressure of 60 +/- 10 mmHg (1.5 Hz) for 4 days. Pressure pulsation induced partial dilation and was associated with less remodeling: 34 +/- 4.0 versus 19 +/- 4.5 microm (P < 0.01) for stable pressure versus oscillating pressure. Vasomotion was frequently observed in all groups, and inward remodeling was larger in vessels with vasomotion: 30 +/- 2.5 microm compared with vessels that did not exhibit vasomotion: 8.0 +/- 5.0 microm (P < 0.01). In conclusion, these results indicate that remodeling is not enhanced by high pressure. Pressure pulsation causes partial dilation and reduces inward remodeling. The appearance of vasomotion is associated with enhanced inward remodeling.     

FTIR study of ATP-induced changes in Na+/K+-ATPase from duck supraorbital glands

The Na+/K+-ATPase uses energy from the hydrolysis of ATP to pump Na+ ions out of and K+ ions into the cell. ATP-induced conformational changes in the protein have been examined in the Na+/K+-ATPase isolated from duck supraorbital salt glands using Fourier transform infrared spectroscopy. Both standard transmission and attenuated total internal reflection sample geometries have been employed. Under transmission conditions, enzyme at 75 mg/ml was incubated with dimethoxybenzoin-caged ATP. ATP was released by flashing with a UV laser pulse at 355 nm, which resulted in a large change in the amide I band. The absorbance at 1659 cm(-1) decreased with a concomitant increase in the absorbance at 1620 cm(-1). These changes are consistent with a partial conversion of protein secondary structure from alpha-helix to beta-sheet. The changes were approximately 8% of the total absorbance, much larger than those seen with other P-type ATPases. Using attenuated total internal reflection Fourier transform infrared spectroscopy, the decrease in absorbance at approximately 1650 cm(-1) was titrated with ATP, and the titration midpoint K0.5 was determined under different ionic conditions. In the presence of metal ions (Na+, Na+ and K+, or Mg2+), K0.5 was on the order of a few microM. In the absence of these ions, K0.5 was an order of magnitude lower (0.1 microM), indicating a higher apparent affinity. This effect suggests that the equilibrium for the ATP-induced conformational changes is dependent on the presence of metal ions.     

Pulsatile blood flow effects on temperature distribution and heat transfer in rigid vessels

The effect of blood velocity pulsations on bioheat transfer is studied. A simple model of a straight rigid blood vessel with unsteady periodic flow is considered. A numerical solution that considers the fully coupled Navier-Stokes and energy equations is used for the simulations. The influence of the pulsation rate on the temperature distribution and energy transport is studied for four typical vessel sizes: aorta, large arteries, terminal arterial branches, and arterioles. The results show that: the pulsating axial velocity produces a pulsating temperature distribution; reversal of flow occurs in the aorta and in large vessels, which produces significant time variation in the temperature profile. Change of the pulsation rate yields a change of the energy transport between the vessel wall and fluid for the large vessels. For the thermally important terminal arteries (0.04-1 mm), velocity pulsations have a small influence on temperature distribution and on the energy transport out of the vessels (8 percent for the Womersley number corresponding to a normal heart rate). Given that there is a small difference between the time-averaged unsteady heat flux due to a pulsating blood velocity and an assumed nonpulsating blood velocity, it is reasonable to assume a nonpulsating blood velocity for the purposes of estimating bioheat transfer.