Role ofl-arginine, a substrate for nitric oxide-synthase, in gastroprotection and ulcer healing

Nitric oxide (NO) synthesized froml-arginine interacts with prostaglandins (PG) and sensory neuropeptides in the regulation of mucosal integrity, but the role ofl-arginine, a substrate for NO-synthase, in gastroprotection and healing of chronic gastric ulcers has been little studied. In this study we compared the effects of intragastric (i.g.) and systemic (i.v.) administration ofl-arginine ord-arginine on gastric secretion and acute gastric lesions provoked in rats by i.g. application of 100% ethanol, acidified aspirin (ASA), or the exposure to 3.5h of water immersion and restraint stress (WRS). In addition, the effects ofl-arginine on ulcer healing and the formation of new vessels (angiogenesis) were determined, using monoclonal antibody (MAb E-9).l-arginine (10–200 mg/kg i.g.) failed to significantly affect gastric secretion but dose-dependently reduced the gastric lesions induced by 100% ethanol, ASA, and WRS, the doses inhibiting 50% of these lesions being 65, 94, and 72 mg/kg, respectively. This protection was accompanied by a significant rise in the gastric blood flow (GBF), whereasl-arginine given i.v. failed to affect the ethanol-lesions and the GBF.d-arginine or the NO-related amino acids—l-glutamine,l-citrulline, orl-ornithine—failed to significantly influence these lesions. Suppression of the generation of mucosal PG by indomethacin or capsaicin-denervation attenuated the protection and hyperemia induced byl-arginine. The inhibition of constitutive NO synthase byl-NNA had no significant effect on the protection afforded byl-arginine, but reduced the gastric hyperemia accompanying this protection.l-arginine (150 mg/kg per day, i.g.) accelerated the ulcer healing and increased GBF at the ulcer margin, and angiogenesis, whereas treatment with L-NNA had an opposite effect.l-arginine added to N^G-nitro-l-arginine (L-NNA) restored the ulcer healing, hyperemia, and angiogenesis. We conclude that: (1) the protective activity ofl-arginine involves gastric hyperemia mediated by NO and a mild irritant effect due to enhanced generation of endogenous PG, and (2) the ulcer healing properties ofl-arginine depend upon its hyperemic and angiogenic actions, possibly involving NO.     

A decrease of enlarged left atrium following cardioversion of atrial fibrillation predicts the long-term maintenance of sinus rhythm

BACKGROUND: Although increased left atrial size (LA) has been long regarded as one of the factors negatively influencing the long-term maintenance of sinus rhythm (SR) following cardioversion (CV) of atrial fibrillation (AF), some reports suggested that CV might be effective also in patients with large LA.Aim. We sought to determine the role of LA enlargement in long-term SR maintenance after CV of persistent AF. METHODS: 104 consecutive patients (33 females, 71 males, mean age 60.4+/-7.4 years) were assigned to SR restoration and maintenance with serial antiarrhythmic drugs. Transthoracic echocardiographic (TTE) variables were recorded prior to CV. Generalised additive logistic regression was used to investigate the impact of LA enlargement on the long-term SR maintenance. RESULTS: SR was present in 63.5% of patients after one year of follow-up. Increased LA area >28 cm (RR 1.72; 1.09-2.71; p<0.02) and increased fractional shortening values in ranges between 26-40% (1.2; 1.01-1.44; p<0.05) were significantly associated with SR maintenance after one year. In order to determine the influence of the LA diameter on the probability of SR maintenance, we analysed mean LA(ar) values prior to and after CV. Patients with large LA(ar) (28 cm(2)) presented a significant decrease of LA size (31.45+/-3.07 cm(2) vs 28.94+/-3.81 cm(2); p<0.008) during the first 30 days after SR restoration. In the group of patients with LA(ar) 28 cm(2) we noted decrease in LA size by 2.57+/-3.2 cm(2), whereas in patients with a smaller LA volume this decrease was significantly lower, being 0.47+/-2.9 cm(2) (p<0.004). CONCLUSIONS: LA enlargement does not preclude a favourable outcome after CV of AF. The decrease in LA area occurring during 30 days following CV favours long term SR maintenance.     

Polymorphisms in TS,MTHFR and ERCC1 genes as predictive markers in first-line platinum and pemetrexed therapy in NSCLC patients

Purpose

We presented retrospective analysis of up to five polymorphisms in TS, MTHFR and ERCC1 genes as molecular predictive markers for homogeneous Caucasian, non-squamous NSCLC patients treated with pemetrexed and platinum front-line chemotherapy.

Methods

The following polymorphisms in DNA isolated from 115 patients were analyzed: various number of 28-bp tandem repeats in 5′-UTR region of TS gene, single nucleotide polymorphism (SNP) within the second tandem repeat of TS gene (G>C); 6-bp deletion in 3′-UTR region of the TS (1494del6); 677C>T SNP in MTHFR; 19007C>T SNP in ERCC1. Molecular examinations’ results were correlated with disease control rate, progression-free survival (PFS) and overall survival.

Results

Polymorphic tandem repeat sequence (2R, 3R) in the enhancer region of TS gene and G>C SNP within the second repeat of 3R allele seem to be important for the effectiveness of platinum and pemetrexed in first-line chemotherapy. The insignificant shortening of PFS in 3R/3R homozygotes as compared to 2R/2R and 2R/3R genotypes were observed, while it was significantly shorter in patients carrying synchronous 3R allele and G nucleotide. The combined analysis of TS VNTR and MTHFR 677C>T SNP revealed shortening of PFS in synchronous carriers of 3R allele in TS and two C alleles in MTHFR. The strongest factors increased the risk of progression were poor PS, weight loss, anemia and synchronous presence of 3R allele and G nucleotide in the second repeat of 3R allele in TS. Moreover, lack of application of second-line chemotherapy, weight loss and poor performance status and above-mentioned genotype of TS gene increased risk of early mortality.

Conclusion

The examined polymorphisms should be accounted as molecular predictor factors for pemetrexed- and platinum-based front-line chemotherapy in non-squamous NSCLC patients.     

Impact of advanced age on myocardial perfusion, distal embolization, and mortality patients with ST-segment elevation myocardial infarction treated by primary angioplasty and glycoprotein IIb–IIIa inhibitors

Despite mechanical reperfusion, the outcome is still unsatisfactory in elderly patients with ST-segment elevation myocardial infarction (STEMI). The vast majority of studies have been conducted without extensive use of glycoprotein (Gp) IIb–IIIa inhibitors, which have been associated with improved perfusion and survival. Thus the aim of the current study was to evaluate the impact of age on the angiographic and clinical outcome patients with STEMI undergoing primary angioplasty with Gp IIb–IIIa inhibitors. Our population is represented by a total of 1,662 patients undergoing primary angioplasty for STEMI included in 11 randomized trials comparing early versus late administration of Gp IIb–IIIa inhibitors. Myocardial perfusion was evaluated by myocardial blush grade and ST-segment resolution. Follow-up data were collected between 30 days and 1 year after primary angioplasty. A total of 231 (13.9 %) patients were older than 75 years. Elderly patients showed a larger prevalence of female gender, hypertension, and diabetes, more advanced Killip class at presentation and longer time to treatment, but a smaller prevalence of smoking. All patients were treated with GP IIb–IIIa inhibitors. Elderly patients showed a significantly impaired postprocedural thrombolysis in myocardial infarction (TIMI) flow (TIMI 0–2: 17.7 vs 10.3 %, P = 0.002) and myocardial perfusion (myocardial blush grade 0–1: 38.3 vs 26.5 %, P = 0.001), and higher prevalence of distal embolization (19.2 vs 9.8 %, P < 0.001), whereas no difference was observed in terms of ST-segment resolution. At follow-up, elderly patients showed a significantly higher mortality (3.2 vs 11.0 %, hazard ratio (HR) (95 % confidence interval (CI)) = 3.78 (2.31–6.16), P < 0.001), which was confirmed after adjustment for baseline confounding factors (HR (95 % CI) = 5.01 (2.63–9.55), P < 0.0001). This study showed that among patients with STEMI undergoing primary angioplasty, advanced age is an independent predictor of mortality after primary angioplasty. Higher rates of distal embolization and poor myocardial perfusion, in addition to the worse risk profile, contribute toward explaining the impact of aging on mortality.     

Synthesis,structural studies and biological properties of some phosphono-perfluorophenylalanine derivatives formed by SNAr reactions

Several novel phosphono-perfluorophenylalanine derivatives, as mimetics of phenylalanine, were synthesized by subjecting diethyl (2-(perfluorophenyl)-1-(phenylamino)ethyl)-phosphonate to S_NAr reactions with different types of nucleophiles such as thiols, amines and phenols. The structure of the products was confirmed using spectroscopic and spectrometric techniques. For two compounds X-ray single crystal diffraction analysis and DFT investigations were performed providing information in regard to the preferable conformation, hydrogen bonds and other interactions. The antiproliferative potency of some of the new phosphono-perfluorophenylalanine derivatives obtained as well as representatives of previously synthesized perfluorophenyl phosphonate analogues of phenylalanine was studied on selected glioma cell lines. Preliminary evaluation of the compounds drug likeness was examined with respect to Lipinski''s and Veber''s rules, and showed that they meet the criteria perfectly. MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide) assay results demonstrated that the compounds exhibit moderate activity against the glioblastoma multiforme cell lines (T98G and U-118 MG). Moreover most of the studied S_NAr reaction products displayed significantly higher inhibitory activity against both cancer cell lines than the parent diethyl (2-(perfluorophenyl)-1-(phenylamino)ethyl)phosphonate.

Several novel phosphono-perfluorophenylalanine derivatives, as mimetics of phenylalanine, were synthesized by subjecting diethyl (2-(perfluorophenyl)-1-(phenylamino)ethyl)-phosphonate to S_NAr reactions with thiols, amines and phenols.     

The prospects of brain — computer interface applications in children

The restoring of motor functions in adults through brain-computer interface applications is widely studied in the contemporary literature. But there is a lack of similar analyses and research on the application of brain-computer interfaces in the neurorehabilitation of children. There is a need for expanded knowledge in the aforementioned area. This article aims at investigating the extent to which the available opportunities in the area of neurorehabilitation and neurological physiotherapy of children with severe neurological deficits using brain-computer interfaces are being applied, including our own concepts, research and observations.     

Bioreactor Study Employing Bacteria with Enhanced Activity toward Cyanobacterial Toxins Microcystins

An important aim of white (grey) biotechnology is bioremediation, where microbes are employed to remove unwanted chemicals. Microcystins (MCs) and other cyanobacterial toxins are not industrial or agricultural pollutants; however, their occurrence as a consequence of human activity and water reservoir eutrophication is regarded as anthropogenic. Microbial degradation of microcystins is suggested as an alternative to chemical and physical methods of their elimination. This paper describes a possible technique of the practical application of the biodegradation process. The idea relies on the utilization of bacteria with a significantly enhanced MC-degradation ability (in comparison with wild strains). The cells of an Escherichia coli laboratory strain expressing microcystinase (MlrA) responsible for the detoxification of MCs were immobilized in alginate beads. The degradation potency of the tested bioreactors was monitored by HPLC detection of linear microcystin LR (MC-LR) as the MlrA degradation product. An open system based on a column filled with alginate-entrapped cells was shown to operate more efficiently than a closed system (alginate beads shaken in a glass container). The maximal degradation rate calculated per one liter of carrier was 219.9 µg h⁻¹ of degraded MC-LR. A comparison of the efficiency of the described system with other biological and chemo-physical proposals suggests that this new idea presents several advantages and is worth investigating in future studies.     

The Accelerated Aging Impact on Mechanical and Thermal Properties of Polypropylene Composites with Sedimentary Rock Opoka-Hybrid Natural Filler

This paper presents the impact of accelerated aging on selected mechanical and thermal properties of isotactic polypropylene (iPP) composites filled with sedimentary hybrid natural filler-Opoka rock. The filler was used in two forms: an industrial raw material originating as a subsieve fraction natural material, and a rock calcinated at 1000 °C for production of phosphorous sorbents. Fillers were incorporated with constant amount of 5 wt % of the resulting composite, and the material was subjected to accelerated weathering tests with different exposition times. The neat polypropylene and composites with calcium carbonate as a reference filler material were used for comparison. The aim of the research was to determine the possibility of using the Opoka rock as a new hybrid filler for polypropylene, which could be an alternative to the widely used calcium carbonate and silica. The thermal, mechanical, and structural properties were evaluated by means of differential scanning calorimetry (DSC), tensile tests, scanning electron microscopy (SEM), and Fourier-transform infrared spectroscopy with attenuated total reflectance (FTIR/ATR) prior to and after accelerated aging. As a result, it was found that the composites of polypropylene with Opoka were characterized by similar or higher functional properties and higher resistance to photodegradation compared to composites with conventional calcium carbonate. The results of measurements of mechanical properties, structural and surface changes, and the carbonyl index as a function of accelerated aging proved that Opoka was an effective ultraviolet (UV) stabilizer, significantly exceeding the reference calcium carbonate in this respect. The new hybrid filler of natural origin in the form of Opoka can therefore be used not only as a typical powder filler, but above all as a UV blocker/stabilizer, thus extending the life of polypropylene composites, especially for outdoor applications.     

Comparison of Numerical Simulation Techniques of Ballistic Ceramics under Projectile Impact Conditions

This article presents an analysis of the effectiveness of available numerical techniques in mapping the characteristic behavior of ballistic ceramics under projectile impact conditions. As part of the work, the ballistic tests were performed on the layered ceramic/steel composite armor and tested with the 7.62 × 39 mm, armor-piercing incendiary (API) BZ projectile. The experimental tests were then mapped using computer simulations. In numerical analyses, four different techniques were used to describe cubic ceramic tiles Al₂O₃ placed on the ARMOX 500T steel backing plate, i.e.,: the Finite Element Method without Erosion (FEM), Finite Element with erosion (FEM + Erosion), Smoothed Particles Hydrodynamics (SPH) and a hybrid method that converts finite elements to SPH particles after exceeding the defined failure criteria (FEM to SPH conversion). The effectiveness of the individual methods was compared in terms of quality (mapping of characteristic phenomena occurring during the penetration process), quantity (bulge height of the backing plate) and time needed to complete the calculations. On the basis of the results of the experiments and numerical simulations, it was noticed that the most accurate reproduction of the phenomenon of ballistic impact of AP projectiles on ceramic/steel composite armor can be obtained by using a hybrid method, incorporating the conversion of finite elements into SPH particles. This method should be used in cases where accuracy of the results is more important than the time required to complete the calculations. In other situations where the purpose of the calculation is not to determine, for example, the exact value of penetration depth but only to observe a certain trend, the FEM method with defined erosion criteria (variant 2), which is more than 10 times faster, can be successfully used.