Effects of Nifedipine on Renal and Cardiovascular Responses to Neuropeptide Y in Anesthetized Rats

Neuropeptide Y (NPY) acts via multiple receptor subtypes termed Y₁, Y₂ and Y₅. While Y₁ receptor-mediated effects, e.g., in the vasculature, are often sensitive to inhibitors of L-type Ca²⁺ channels such as nifedipine, little is known about the role of such channels in Y₅-mediated effects such as diuresis and natriuresis. Therefore, we explored whether nifedipine affects NPY-induced diuresis and natriuresis. After pre-treatment with nifedipine or vehicle, anesthetized rats received infusions or bolus injections of NPY. Infusion NPY (1 µg/kg/min) increased diuresis and natriuresis, and this was attenuated by intraperitoneal injection of nifedipine (3 µg/kg). Concomitant decreases in heart rate and reductions of renal blood flow were not attenuated by nifedipine. Bolus injections of NPY (0.3, 1, 3, 10 and 30 μg/kg) dose-dependently increased mean arterial pressure and renovascular vascular resistance; only the higher dose of nifedipine (100 μg/kg/min i.v.) moderately inhibited these effects. We conclude that Y₅-mediated diuresis and natriuresis are more sensitive to inhibition by nifedipine than Y₁-mediated renovascular effects. Whether this reflects a general sensitivity of Y₅ receptor-mediated responses or is specific for diuresis and natriuresis remains to be investigated.     

Gold glyconanoparticles for mimics and measurement of metal ion-mediated carbohydrate-carbohydrate interactions

To mimic and measure calcium ion-mediated carbohydrate-carbohydrate interactions, four lactose derivatives have been synthesized for assembly on gold nanoparticles. The series of lactose derivatives varied by the length of the thiolated ethylene glycol anchor chain [O(CH2CH2O)(m)CH2CH2SH; where m = 0, 1, 2, and 3] used to self-assemble the carbohydrates to the preformed gold nanoparticles of ca. 16 nm diameter. Upon addition of calcium ions to the lactose-stabilized nanoparticles, rapid carbohydrate-carbohydrate interactions were visualized and subsequently measured using UV-visible spectrometry and transmission electron microscopy (TEM). The nanoparticle aggregates formed via metal-mediated carbohydrate-carbohydrate interactions could be readily redispersed through the addition of EDTA. Multiple reaggregation and redispersion cycles were achieved, confirming that the aggregation process was due to metal ion-mediated carbohydrate interactions rather than calcium chelation by residual citrate ions on the particle surface. The essential involvement of the lactose moiety in Ca2+ complexation was shown by control measurements on related D-glucose-derivatized nanoparticles, where a significantly reduced aggregation response was obtained only at high ion concentrations. Other group 2 metal ions with radii larger than that of calcium, viz., barium and strontium, were also shown to mediate the aggregation of the lactose-stabilized nanoparticles. The induced aggregation of the lactose nanoparticles was determined to be quantitatively dependent upon the calcium ion concentration. Furthermore, the analytical sensitivity of the calcium-induced aggregation and the linear dynamic range were dependent on the length of the ethylene glycol anchor chain. The shortest ethylene glycol chain (m = 0) gave the most sensitive response with the optimum limit of detection (0.8 mM Ca2+), whereas the longest ethylene glycol chain (m = 3) provides a measurement of calcium ion concentration over the largest linear dynamic range (10-35 mM Ca2+). This work has shown that the self-assembled deposition of lactose derivatives on gold nanoparticles provides multivalent carbohydrate surfaces that can be used as mimics for the measurement of biologically relevant carbohydrate-carbohydrate interactions. Additionally, this study has highlighted the importance of the structure and length of the ligand that anchors the carbohydrate sugar to the gold particle surface to facilitate such carbohydrate interactions and for "tuning" the analytical characteristics of bioassays developed using metal nanoparticle technology.     

Cycle Lengths in Hamiltonian Graphs with a Pair of Vertices Having Large Degree Sum

A graph of order n is said to be pancyclic if it contains cycles of all lengths from three to n. Let G be a Hamiltonian graph and let x and y be vertices of G that are consecutive on some Hamiltonian cycle in G. Hakimi and Schmeichel showed (J Combin Theory Ser B 45:99–107, 1988) that if d(x) + d(y) ≥ n then either G is pancyclic, G has cycles of all lengths except n − 1 or G is isomorphic to a complete bipartite graph. In this paper, we study the existence of cycles of various lengths in a Hamiltonian graph G given the existence of a pair of vertices that have a high degree sum but are not adjacent on any Hamiltonian cycle in G.     

Reactivity of 4‐thiothymidine with Fenton reagent investigated by UV‐visible spectroscopy and electrospray ionization mass spectrometry

The reactivity of the sulfur‐containing nucleoside 4‐thio‐(2′‐deoxy)‐thymidine usually abbreviated as 4‐thio‐thymidine, (S⁴‐TdR) under Fenton conditions, ie, in the presence of H₂O₂ and catalytic amounts of Fe(II), was investigated by UV‐vis spectroscopy and electrospray ionization single and tandem mass spectrometry (ESI‐MS and MS/MS). S⁴‐TdR hydroxylated on the S atom was found to be a key reaction intermediate, ultimately leading to (2′‐deoxy)‐thymidine usually abbreviated as thymidine, (TdR) as the main reaction product. This finding was in accordance with the outcome of the reaction between S⁴‐TdR and H₂O₂, previously investigated in our laboratory. On the other hand, the additional presence of ?OH radicals, induced by the Fe(II)/H₂O₂ combination, led to the increased generation of another interesting S⁴‐TdR product, already observed after its reaction with H₂O₂ alone, ie, the covalent dimer including a S? S bridge between two S⁴‐TdR molecules. More importantly, multihydroxylated derivatives of S⁴‐TdR and TdR were detected as peculiar products obtained under Fenton conditions. Among them, a product bearing an OH group both on the methyl group linked to the thymine ring and on the C5 atom of the ring was found to prevail. The results obtained during this study, integrated by those found previously in our laboratory, indicate 4‐thiothymidine as a promising molecular probe for the recognition, through a careful characterization of its reaction products, of the prevailing species among reactive oxygen species (ROS) corresponding to singlet‐state oxygen, hydrogen peroxide, and hydroxylic radical.     

Electropolymerizable IrIII Complexes with β‐Ketoiminate Ancillary Ligands

A series of electropolymerizable cyclometallated Ir^III complexes were synthesized and their electrochemical and photophysical properties studied. The triphenylamine electropolymerizable fragment was introduced by using triphenylamine‐2‐phenylpyridine and, respectively, triphenylamine‐benzothiazole as cyclometalated ligands. The coordination sphere was completed by two differently substituted β‐ketoiminate ligands deriving from the condensation of acetylacetone or hexafluoroacetylacetone with para‐bromoaniline. The influence of the ‐CH₃/‐CF₃ substitution to the electrochemical and photophysical properties was investigated. Both complexes with CH₃ substituted β‐ketoiminate were emissive in solution and in solid state. Highly stable films were electrodeposited onto ITO coated glass substrates. Their emission was quenched by electron trapping within the polymeric network as proven by electrochemical studies. The ‐CF₃ substitution of the β‐ketoiminate leads instead to the quenching of the emission and inhibits electropolymerization.     

Synthesis and Pharmacological Screening of Pyridopyrimidines as Effective Anti-Diarrheal Agents through the Suppression of Cyclic Nucleotide Accumulation

The increased levels of cyclic nucleotides (cGMP and cAMP) in enterocytes trigger intracellular mechanisms of ion and fluid secretion into the lumen, causing secretory diarrhea. Twelve novel pyridopyrimidines derived from 5-(3,5-bistrifluoromethylphenyl)-1,3-dimethyl-5,11-dihydro-1H-indeno[2,1 : 5,6]pyrido[2,3-d]pyrimidine-2,4,6-trione (FPIPP) were synthesized and evaluated on intracellular cyclic nucleotide accumulation. All compounds had no effect on either cyclic nucleotide basal levels or on pre-contracted aortic rings. The metabolic activity and viability in T84 cells, assessed by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) and the LDH (lactate dehydrogenase) assays, respectively, were not affected by incubation with the compounds (50 μM). Compound VI almost abolished cGMP accumulation (94 % inhibition) induced by STa toxin in T834 cells and significantly reduced (69 %) forskolin-induced cAMP accumulation in Jurkat cells. Compound VI was active in an in vivo model for diarrhea in rabbits. These results prompted us to perform a microscopic histopathological analysis of intestinal tissues, showing that only compound VI preserves the intestine without significant pathological changes and with a decreased inflammatory pattern in comparison to FPIPP. In vitro stability test revealed that compound VI is resistant to oxidation promoted by atmospheric oxygen.     

Magnetic Carbon Composite Particles for Dye Adsorption from Water and their Electrochemical Regeneration

Herein, the development of a novel composite particle system prepared from superparamagnetic Fe₃O₄@SiO₂ microparticles as core and coated with a carbon shell is presented. The coating with carbon is done by pyrolyzing furan resin, which was previously deposited on the particle surface by poly‐merization of furfuryl alcohol. The novel composite material thus combines magnetic and sorptive properties. Upon pyrolysis the magnetic material is converted from magnetite to α‐iron and fayalite, changing its behavior from superparamagnetic to ferromagnetic with nearly zero remanence. The magnetic properties can be utilized to magnetically collect the particles dispersed in fluids, whereas the sorptive properties of the carbon shell can be used to remove organic contaminants from these fluids. The adsorption behavior of the composite particles and a potential electrochemical regeneration route are investigated, using the model dye methylene blue.     

Status of an R&D project of a positron gun at “Horia Hulubei” NIPNE Bucharest

A new positron gun (PG) will enable high sensitivity measurements in applications of positron annihilation spectroscopy in Romania. Some data concerning the design of a modular system for focussing, transport and acceleration of mono-energetic positrons in the range 0.8-50 keV have been obtained and experimenting on moderators and CDBS was performed. We present a short overview of the present status of the project and preliminary results from Coincidence Doppler Broadening Spectroscopy with a ²²NaCl source, on Al samples. The entire positron gun system will be designed as a high-vacuum dedicated extension operating with two options: a 50 mCi ²²NaCl source and in-line with the NIPNE cyclotron or a new intense compact cyclotron.     

A constraint on wave,radial and shock velocities in nonlinear electromagnetic materials

In a non linear electromagnetic isotropic medium the wave, radial and shock velocities do not exceed light speed iff some simple conditions are satisfied.

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Sunto Si danno condizioni necessarie e sufficienti par la limitatezza delle vélocitá d'onda, radiale e d'urto nei materiali elettromagnetici isotropi non lineari.