Iloprost preserves kidney function against anoxia

Tissue protective activity of iloprost against anoxia was studied in the isolated perfused rabbit kidney. Addition of iloprost to the perfusion medium at concentrations between 10(-9)-10(-7) M attenuated the release of noradrenaline due to periarterial stimulation and decreased urine outflow. Iloprost also caused a concentration-dependent decrease in perfusion pressure. The potentiation by angiotensin II of the vasoconstriction due to periarterial stimulation and increase in urine volume were also decreased by further addition of iloprost into the medium. Iloprost at concentrations below 10(-7) M did not alter the vasoconstrictor effect of exogenously applied noradrenaline. UK 38 485, a powerful thromboxane A2 synthetase inhibitor, significantly suppressed the vascular but greatly potentiated the diuretic effects of angiotensin II. In kidneys exposed to anoxia for 24 hours in Krebs medium, the vascular and diuretic effects of angiotensin II and the release of noradrenaline due to periarterial stimulation were significantly diminished. In addition, interation between UK 38 485 and angiotensin II in both perfusion pressure and urine volume was also reduced after anoxia for 24 hours. On the other hand, no significant loss was observed in all investigated parameters measured in this study, in kidneys exposed to anoxia for 48 hours in the presence of iloprost. From these results it was concluded that iloprost preserves kidneys functionally against anoxia and possible mechanisms of this effect are discussed.     

The alterations of leukotriene C4 and prostaglandin E2 levels following different ischemic periods in rat brain tissue

Leukotrienes and prostaglandins are formed from arachidonic acid by activation of local phospholipases in pathological conditions such as cerebral ischemia, subarachnoid hemorrhage, cerebral tumors and seizures. These mediators, especially leukotrienes have a very potent vasoconstrictor effect on cerebral arteries. Experimental studies have shown that this effect, by increasing vascular permeability causes vasogenic edema that contributes to the ischemic penumbra. In this study, after developing an experimental animal model simulating the concept of ischemic penumbra in the rat, the levels of leukotriene C and prostaglandin E2 produced in the forebrain were measured and the effects of these mediators in prolonged ischemia were investigated. The results, in the first 4 min of ischemia, showed that the arachidonic acid metabolites, particularly, leukotriene C4, reached a peak in the ischemic cerebral tissue in association with leukocyte accumulation. Later in the 15th min, significant decreases in leukotriene C4 and prostaglandin E2 levels were seen. In the 1st and 4th h, probably due to the stimulation of the relevant enzymes by free oxygen radicals in the ischemic tissue; the levels increase again, returning to control values by the 12th h. It is concluded that the use of lipoxygenase inhibitors and free radical scavengers may be helpful to limit the infarct area in the first 4 h of ischemia.     

Schiff Base Derivatives of 4-Aminoantipyrine as Promising Molecules: Synthesis,Structural Characterization,and Biological Activities

Russian Journal of Bioorganic Chemistry - In this study, some Schiff bases derived from 4-aminoantipyrine (4-AAP) (VI–X) were synthesized, characterized by elemental analysis (C, H, N) and...     

Study of the TmoS/TmoT two‐component system: towards the functional characterization of the family of TodS/TodT like systems

The two‐component system TmoS/TmoT controls the expression of the toluene‐4‐monooxygenase pathway in Pseudomonas mendocina RK1 via modulation of P_tmoX activity. The TmoS/TmoT system belongs to the family of TodS/TodT like proteins. The sensor kinase TmoS is a 108 kDa protein composed of seven different domains. Using isothermal titration calorimetry we show that purified TmoS binds a wide range of aromatic compounds with high affinities. Tightest ligand binding was observed for toluene (K_D = 150 nM), which corresponds to the highest affinity measured between an effector and a sensor kinase. Other compounds with affinities in the nanomolar range include benzene, the 3 xylene isomers, styrene, nitrobenzene or p‐chlorotoluene. We demonstrate that only part of the ligands that bind to TmoS increase protein autophosphorylation in vitro and consequently pathway expression in vivo. These compounds are referred to as agonists. Other TmoS ligands, termed antagonists, failed to increase TmoS autophosphorylation, which resulted in their incapacity to stimulate gene expression in vivo. We also show that TmoS saturated with different agonists differs in their autokinase activities. The effector screening of gene expression showed that promoter activity of P_tmoX and P_todX (controlled by the TodS/TodT system) is mediated by the same set of 22 compounds. The common structural feature of these compounds is the presence of a single aromatic ring. Among these ligands, toluene was the most potent inducer of both promoter activities. Information on the TmoS/TmoT and TodS/TodT system combined with a sequence analysis of family members permits to identify distinct features that define this protein family.     

Maximum likelihood estimation of the kinetics of receptor-mediated adhesion

Adhesion flow assays are commonly employed to characterize the kinetics and force-dependence of receptor-ligand interactions. As transient cellular adhesion events are often mediated by a small number of receptor-ligand complexes (tether bonds) their durations are highly variable, which in turn presents obstacles to standard methods of analysis. In this paper, we employ the stochastic approach to chemical kinetics to construct the pause time distribution. Using this distribution, we develop a robust maximum likelihood (ML) approach to the robust estimation of rate constants associated with receptor-mediated transient adhesion and their confidence intervals. We then formulate robust estimators of the parameters of models for the force-dependence of the off-rate. Lastly, we develop a robust method of elucidation of the force-dependence of the off-rate using Akaike's information criterion (AIC). Our findings conclusively demonstrate that ML estimators of adhesion kinetics are substantial improvements over more conventional approaches, and when combined with Fisher information, they may be used to objectively and reproducibly distinguish the kinetics of different receptor-ligand complexes. Software for the implementation of these methods with experimental data is publicly available as for download at http://www.laurenzi.net.