New horizon in dialysis depuration: Characterization of a polysulfone membrane able to break the 'albumin wall'.

The uremic syndrome is attributed to the progressive retention of a large number of toxins, which under normal conditions are excreted by the healthy kidneys. Standard dialytic membranes do not purify middle-high molecular weight toxins. Haemodiafiltration with endogenous reinfusion coupled with a highly permeable membrane could break the limit of the 'albumin wall' improving the dialytic depuration without loss of important nutrients. The aim of this study was to evaluate the performance of a new polysulfone membrane, Synclear 0.2, to remove uremic molecules. Surface Enhanced Laser Desorption Ionization-Time of Flight was employed to evaluate the proteomic profile of ultrafiltrate and Electrospray Ionization-Quadruple-ToF coupled with on-chip elution was used for proteins identification. A high and specific permeability for middle-high molecular weight molecules was revealed by mass spectrometry for the investigated membrane. The identified proteins are mostly uremic toxins: their relative abundance, estimated in the ultrafiltrate by exponentially modified protein abundance index, showed a high purification efficiency of the new membrane when compared with conventional ones. In conclusion, Synclear 0.2, used as convective membrane in hemodiafiltration with endogenous reinfusion treatment, permits to break the 'albumin wall', clearing middle-high molecular weight uremic toxins, improving the dialytic treatment purification efficiency.

An unusual case of signet ring cell adenocarcinoma of the prostate.

We report the case of a 70-year-old man with symptoms of urinary obstruction and haematuria, with histological diagnosis of primary signet-ring cell carcinoma of the prostate. Almost 90% of the tumour cells contained characteristic intracytoplasmic vacuoles that positively stained with diastase-digested PAS, Alcian blue and mucicarmine. The positive immunostaining for PSA and PSAP confirmed the prostatic origin of the tumour. Although the patient received hormonal therapy, the disease progressed and the patient died 11 months after surgery.

Tunable Tsallis distributions in dissipative optical lattices.

We demonstrated experimentally that the momentum distribution of cold atoms in dissipative optical lattices is a Tsallis distribution. The parameters of the distribution can be continuously varied by changing the parameters of the optical potential. In particular, by changing the depth of the optical lattice, it is possible to change the momentum distribution from Gaussian, at deep potentials, to a power-law tail distribution at shallow optical potentials.

Dissipation-induced symmetry breaking in a driven optical lattice.

We analyze the atomic dynamics in an ac driven periodic optical potential which is symmetric in both time and space. We experimentally demonstrate that in the presence of dissipation the symmetry is broken, and a current of atoms through the optical lattice is generated as a result.

Resonant activation in a nonadiabatically driven optical lattice.

We demonstrate the phenomenon of resonant activation in a nonadiabatically driven dissipative optical lattice with broken time symmetry. The resonant activation results in a resonance as a function of the driving frequency in the current of atoms through the periodic potential. We demonstrate that the resonance is produced by the interplay between deterministic driving and fluctuations, and we also show that by changing the frequency of the driving it is possible to control the direction of the diffusion.

Controlled single-photon emission from a single trapped two-level atom.

By illuminating an individual rubidium atom stored in a tight optical tweezer with short resonant light pulses, we created an efficient triggered source of single photons with a well-defined polarization. The measured intensity correlation of the emitted light pulses exhibits almost perfect antibunching. Such a source of high-rate, fully controlled single-photon pulses has many potential applications for quantum information processing.

Antioxidant activity of carotenoids: an electron-spin resonance study on beta-carotene and lutein interaction with free radicals generated in a chemical system.

beta-Carotene is thought to be a chain-breaking antioxidant, even though we have no information about the mechanism of its antioxidant activity. Using electron-spin resonance (ESR) spectroscopy coupled to the spin-trapping technique, we have studied the effect of beta-carotene and lutein on the radical adducts of the spin-trap PBN (N-t-butyl-alpha-phenylnitrone) generated by the metal-ion breakdown of different tert-butyl hydroperoxide (tBOOH) concentrations in methylene chloride. The peroxyl radical, along with an oxidation product of PBN (the PBNOx), trapped at room temperature from the breakdown of high concentration of tBOOH (1 M), were quenched by beta-carotene or lutein, in competition with the spin-trapping agent. However, carotenoids were not able to quench the alkoxyl and methyl radicals generated in the reaction carried out in the presence of low tBOOH concentration (1 mM). The reaction between carotenoids and the peroxyl radical was also carried out in the absence of the spin trap, at 77 K: Under these different experimental conditions, we did not detect any radical species deriving from carotenoids. In the same system, a further evidence of the peroxyl radical quenching by beta-carotene and lutein was obtained. The antioxidant activity of vitamin E was also tested, for comparison with the carotenoids. In the presence of alpha-tocopherol, peroxyl and alkoxyl radicals were quenched, and the tocopheroxyl radical was detected. Our data provide the first direct evidence that carotenoids quench peroxyl radicals. Under our experimental conditions, we did not detect any carotenoid radical species that could derive from the interaction with the peroxyl radical. The radical-trapping activity of beta-carotene and lutein demonstrated in this chemical reaction contributes to our understanding carotenoid antioxidant action in biological systems.

Prooxidant activity of ferrioxamine in isolated rat hepatocytes and linoleic acid micelles.

The complex iron-desferrioxamine (ferrioxamine) is considered chemically unreactive, and not able to participate in redox cycle reactions. Desferrioxamine-dependent toxicity is, however, described in both human and animal studies. The aim of this work was to test the possibility that chelated iron, under certain circumstances, could enter redox reactions, giving an explanation of desferrioxamine side effects. Carefully prepared ferrioxamine, to obtain a 1:1 desferrioxamine:iron ratio, was added to isolated rat hepatocytes and to linoleic acid micelles. A strong prooxidant and cytotoxic effect was observed in the cells, also potentiating tert-butyl hydroperoxide-induced lipid peroxidation. In micelles, the prooxidant effect was observed only in the presence of ascorbate, which is oxidized during the process, giving rise to ascorbyl radical. Ferrioxamine, under the experimental conditions used, did not release iron, indicating that the prooxidant effect was due to iron redox cycling. The addition of desferrioxamine prevented both ferrioxamine- and tert-butyl hydroperoxide-induced lipid peroxidation and cytotoxicity. Concurrently, a nitroxide radical was detected, an indication of the radical scavenger activity of the hydroxamic moiety. No radical species was observed when ferrioxamine was added to the same system. The prooxidant effect of ferrioxamine gives a possible explanation of the reported human and animal desferrioxamine toxicity. When, in compartmentalized regions, the ratio of desferrioxamine:metal reaches 1:1, ferrioxamine is formed. In the absence of metal-free desferrioxamine, ferrioxamine can participate in redox cycling reactions, initiating lipid peroxidation and cytotoxicity.

Influence of different hemodialysis membranes on red blood cell susceptibility to oxidative stress.

Oxidative stress is crucial in red blood cell (RBC) damage induced by activated neutrophils in in vitro experiments. The aim of the study was to evaluate whether the bioincompatibility phenomena occurring during hemodialysis (HD) (where neutrophil activation with increased free radical production is well documented) may have detrimental effects on RBC. We evaluated RBC susceptibility to oxidative stress before and after HD in 15 patients using Cuprophan, cellulose triacetate, and polysulfone membrane. RBC were incubated with t-butyl hydroperoxide as an oxidizing agent both in the presence and in the absence of the catalase inhibitor sodium azide. The level of malonaldehyde (MDA), a product of lipid peroxidation, was measured at 0, 5, 10, 15, and 30 min of incubation. When Cuprophan membrane was used, the MDA production was significantly higher after HD, indicating an increased susceptibility to oxidative stress in comparison to pre-HD. The addition of sodium azide enhanced this phenomenon. Both cellulose triacetate and polysulfone membranes did not significantly influence RBC susceptibility to oxidative stress. Neither the level of RBC reduced glutathione nor the RBC glutathione redox ratio changed significantly during HD with any of the membranes used. The RBC susceptibility to oxidative stress was influenced in different ways according to the dialysis membrane used, being increased only when using the more bioincompatible membrane Cuprophan, where neutrophil activation with increased free radical production is well documented. The alterations found in this study might contribute to the reduced RBC longevity of HD patients where a bioincompatible membrane is used.

The highly reducing sugar 2-deoxy-D-ribose induces apoptosis in human fibroblasts by reduced glutathione depletion and cytoskeletal disruption.

2-deoxy-D-Ribose (dRib), the most reducing sugar, induces apoptosis in normal human fibroblasts, as judged by cytoplasmic shrinkage, chromatin condensation, DNA fragmentation and mitochondrial depolarization. This effect is independent from culture conditions, such as cell density and the presence or absence of serum in the culture milieu, suggesting that dRib-induced apoptosis is cell cycle-independent. dRib was found also to provoke disruption of the actin filament network and detachment from the substratum, while at the same time, interestingly, it increases the expression of several integrins and cell adhesion molecules. Furthermore, dRib was found to reduce the intracellular levels of reduced glutathione (GSH). The apoptotic process was not affected by the macromolecular-synthesis inhibitors cycloheximide and actinomycin D. On the contrary, the antioxidant N-acetyl-L-cysteine (NAC) fully blocks the dRib-induced apoptosis by preventing GSH depletion, while it also inhibits actin-filament-network disruption and mitochondrial depolarization. The above indicate that dRib induces apoptosis in human fibroblasts by a mechanism involving glutathione metabolism and oxidative stress, as well as disturbance of cytoskeletal integrity and cell adhesion.

N-acetylcysteine inhibits in vivo nitric oxide production by inducible nitric oxide synthase.

This in vivo study evaluates the effect of N-acetylcysteine (NAC) administration on nitric oxide (NO) production by the inducible form of nitric oxide synthase (iNOS). NO production was induced in the rat by the ip administration of 2 mg/100 g lipopolysaccharide (LPS). This treatment caused: (1) a decrease in body temperature within 90 min, followed by a slow return to normal levels; (2) an increase in plasma levels of urea, nitrite/nitrate, and citrulline; (3) the appearance in blood of nitrosyl-hemoglobin (NO-Hb) and in liver of dinitrosyl-iron-dithiolate complexes (DNIC); and (4) increased expression of iNOS mRNA in peripheral blood mononuclear cells (PBMC). Rat treatment with 15 mg/100 g NAC ip, 30 min before LPS, resulted in a significant decrease in blood NO-Hb levels, plasma nitrite/nitrate and citrulline concentrations, and liver DNIC complexes. PBMC also showed a decreased expression of iNOS mRNA. NAC pretreatment did not modify the increased levels of plasma urea or the hypothermic effect induced by the endotoxin. The administration of NAC following LPS intoxication (15 min prior to sacrifice) did not affect NO-Hb levels. These results demonstrate that NAC administration can modulate the massive NO production induced by LPS. This can be attributed mostly to the inhibitory effect of NAC on one of the events leading to iNOS protein expression. This hypothesis is also supported by the lack of effect of late NAC administration.

El criterio cardiopatía de base en el diagnóstico diferencial de las taquicardias con QRS ancho / The criterion cardiopathy of base in the differencial diagnostic of the tachicardia with TQA

El diagnóstico diferencial de las taquicardias con QRS ancho se basa clásicamente en una serie de criterios electrográficos complejos, difíciles de recordar, que requieren cierto entrenamiento, todo lo cual limita su utilidad práctica y conducen con frecuencia a errores diagnósticos. Se trabajó sobre la hipótesis de que el diagnóstico de las taquicardias con QRS ancho se torna más sencillo y seguro a partir del análisis de ECG de base que el ECG de la taquicardia misma. Se analizaron 45 taquicardias con QRS ancho cuyo origen estaba certificado por estudios electrofisiológicos, en busca de criterios descriptos para el diagnóstico diferencial, considerando además la existencia o no de cardiopatía orgánica de base. Se halló que la presencia de cardiopatía de base predecía mejor que cualquier otra variable el diagnóstico de taquicardia ventricular (VT). En casi la totalidad de los casos, la cardiopatía de base se hallaba manifiesta en la ECG de base. La ausencia de cardiopatía de base no excluyó al diagnóstico de TV, aunque esto fue poco frecuente. La presencia de cardiopatía de base no permitió excluir una taquicardia supraventricular (TSV), si bien ello no presentó un problema de diagnóstico, ya que la mayoría de las TVS con cardiopatía de base mostraban un patrón de pre-exitación en el ECG de base. Se concluye que la presencia de cardiopatía de base, detectable por el ECG de base u otros parámetros clínicos, es un criterio simple, fácil de recordar y de alto valor predictivo para el diagnóstico de TV. Adquiere así mayor valor el ECG de base que el ECG de la propia taquicardia. Este enfoque simplificado torna más accesible el diagnóstico diferencial de las taquicardias con QRS ancho