Zs. Márton

Pituitary adenylate cyclase activating polypeptide in the retina: focus on the retinoprotective effects.

Pituitary adenylate cyclase activating polypeptide (PACAP) is a neurotrophic and neuroprotective peptide that has been shown to exert protective effects against different neuronal injuries, such as traumatic brain and spinal cord injury, models of neurodegenerative diseases, and cerebral ischemia. PACAP and its receptors are present in the retina. In this study, we summarize the current knowledge on retinal PACAP with focus on the retinoprotective effects. Results of histological, immunohistochemical, and molecular biological analysis are reviewed. In vitro, PACAP shows protection against glutamate, thapsigargin, anisomycin, and anoxia. In vivo, the protective effects of intravitreal PACAP treatment have been shown in the following models of retinal degeneration in rats: excitotoxic injury induced by glutamate and kainate, ischemic injury, degeneration caused by UV‐A light, optic nerve transection, and streptozotocin‐induced diabetic retinopathy. Studying the molecular mechanism has revealed that PACAP acts by activating antiapoptotic and inhibiting proapoptotic signaling pathways in the retina in vivo. These studies strongly suggest that PACAP is an excellent candidate retinoprotective agent that could be a potential therapeutic substance in various retinal diseases.

A comparative study of size-distribution of nanoparticles generated by laser ablation of graphite and tungsten

Abstract Nanoparticles (NPs) were generated by ArF excimer laser ablation of graphite and tungsten targets in N2 ambient at atmospheric pressure. The size distribution of the particles was monitored in situ by a scanning mobility particle sizer (SMPS) system, based on differential mobility analyser. The experimental conditions made possible to record the size distributions in the 7–133-nm diameter range and results are presented for different laser fluences, repetition rates and ablated areas, respectively. Material analysis was performed by photoelectron spectroscopy (XPS), Raman spectroscopy, X ray diffraction and SEM.

Raman spectroscopic and atomic force microscopic study of graphite ablation at 193 and 248 nm

Experimental results are presented for the excimer laser ablation of highly oriented pyrolytic graphite at 193 and 248 nm for both single pulses and pulse trains in the fluence range of ∼1–15 J/cm2. The morphology and the depth of the ablated pits are monitored by atomic force microscopy, while the material characterization is performed by micro-Raman spectroscopy. A shift from ∼1.12 to ∼2.23 J/cm2 laser fluence is found in the single shot ablation threshold for the 248 nm laser wavelength compared to that at 193 nm. Broad D and G peaks in the Raman spectra indicate the formation of amorphous carbon layers as a result of laser irradiation with 193 and 248 nm pulses. This amorphous layer is present at lower fluences (several J/cm2) and after the very first shots. The modified layer created at 193 nm, compared to 248 nm, consists of optically denser material having more turbostratical/glassy character. The spectra do not show significant changes for fluences exceeding 6–7 J/cm2. A several hundred nanometers-high ring-like structure can be observed around the ablated pits. For laser fluences in excess of the estimated threshold at ∼6 J/cm2 (close to the aforementioned limit), the diameter of this structure increases with laser fluence. One hypothesis to explain the ring formation and the saturation of the Raman spectra supposes that the graphite melts and squirts on the laser irradiation. The ring, debris material and the amorphous layers disappear after heat treatment of the samples at 650°C, most probably by oxidative etching.

The role of hemorheological factors in cardiovascular medicine

Cardiovascular diseases (CVD) are the most frequent cause of death throughout the world. The coronary vessel system is a special part of the circulation since there is a continuous change in blood flow, perfusion pressure and shear rate during each cardiac cycle. It is also the place of the narrowest capillaries in the human body, therefore the role of rheological alterations may be of greater importance than in the other parts of the circulatory system. During the past decades, our group has investigated hemorheological parameters (HP) in over 1,000 patients diagnosed with various forms of ischemic heart disease (IHD). In one prospective study, we measured the HP of patients with acute coronary syndrome (ACS). On admission, all examined variables were significantly worse than those of control subjects. During the hospital phase, some of the HP showed further deterioration, and HP remained in the pathologic range during the follow-up period. In another study, we showed that HP are in close correlation with the severity of coronary artery disease. In patients treated with percutaneous coronary intervention, changes in HP were very similar to those observed in subjects with ACS. In a recent study, we analyzed HP in patients undergoing CABG surgery. Our data suggest a hemorheological advantage of off-pump surgery. In another study low Hct/WBV ratio can be regarded as a risk factor of cardiac death in IHD. Our data indicate that rheological parameters are significantly altered in patients with IHD: the extent of the alterations is in excellent correlation with the clinical severity of the disease. Our findings prove that HP play a critical role in the pathogenesis of myocardial ischemia. In recent in vitro and in vivo studies we have investigated the effects of red wine on hemorheological parameters. Our results show that moderate red wine consumption has beneficial effects on hemorheological parameters which may contribute to the French paradox.

In vitro hemorheological effects of red wine and alcohol-free red wine extract.

The French paradox is based on epidemiological evidence which supports that moderate red wine consumption reduces the risk of cardiovascular diseases. A number of experimental animal studies reported favourable cardiovascular effects of alcohol-free red wine extract (AFRW). Our study was designed to determine red wine and AFRW induced changes in various hemorheological parameters. These effects may play a role in the pathophysiology of the French paradox regarding the cardiovascular protective impacts of red wine. Blood samples of healthy volunteers were mixed with red wine to achieve alcohol concentrations of 1 per thousand, 3 per thousand and 10 per thousand, respectively, with equivalent amount of AFRW or physiological saline. Blood samples were pretreated with red wine or AFRW in order to prove the protective effects on erythrocytes from impairment of deformability caused by the free radical generator phenazine methosulfate (PMS). Erythrocyte aggregation (Myrenne and LORCA), deformability (LORCA) and platelet aggregation (Carat TX4) were measured. Erythrocyte aggregation using Myrenne aggregometer was inhibited by red wine and AFRW compared to the saline treated samples. The difference reached already significance at 1 per thousand concentration at the AFRW samples (p < 0.05). Furthermore, red wine caused stronger inhibition than AFRW. The difference between the two agents became significant at 10 per thousand concentration (p < 0.05). LORCA aggregation index and threshold shear rate supported these results at the highest concentration. Erythrocyte deformability of healthy volunteers did not change significantly for any concentrations of red wine and AFRW. On the other hand AFRW at 3 per thousand concentration significantly prevented erythrocytes from impairment of deformability caused by PMS (p < 0.05). Platelet aggregation was significantly inhibited by the highest concentration of AFRW (p < 0.05). Our results show that red wine and AFRW have some beneficial effects on hemorheological parameters that may contribute to the French paradox.

In situ monitoring of size distributions and characterization of nanoparticles during W ablation in N2 atmosphere

Nanoparticles were generated by pulsed laser ablation of tungsten in a N2 ambient at atmospheric pressure. Size distributions and concentrations were monitored in situ versus laser fluence, repetition rate, and ablated spot size, by a differential mobility analyzer and a particle counter. The multishot ablation threshold was determined to be ∼6 J/cm2 for the laser used (ArF excimer, λ=193 nm). Mostly small, nonlognormally, distributed particles ( 20 nm in diameter) increased above φth. Modeling of the temperature and ablated depth dependence on fluence showed that the formation of clusters below φth could not be assigned to a thermal process, but are connected to particle condensation from a photochemically desorbed thin layer. X-ray diffraction and x-ray photoelectron spectroscopy analysis performed on polydisperse nanoparticles revealed an amorphous phase of the particles, and th...

Reviewing data reduction methods for ektacytometry

Ektacytometry quantifies erythrocyte deformability by measuring the elongation of suspended red blood cells subjected to a range of shear stresses. Raw shear stress-elongation index plots are difficult to interpret and thus data reduction methods characterizing the relationship using few parameters without loss of information and good reproducibility are essential, especially for the clinician. Two such curve fitting formulas, used widely in the literature for this purpose, are reviewed herein. The Lineweaver-Burke method overestimates maximal deformability if shear stresses below 1 Pa are applied. A modified version of the formula estimates maximal deformation more accurately but gives little weight to data at low shear stresses. Neither method is accurate if negative elongation indices are present (artifact phenomenon when measurement is performed from high to low shear stresses). The Streekstra-Bronkhorst method provides efficient data reduction though the theoretical background of the formula is incorrect. The parameters have expressive meaning; however, both maximal and minimal deformations are slightly underestimated. Moreover, parameters are biased according to the range of measured shear stresses.