A paternal methyl donor-rich diet altered cognitive and neural functions in offspring mice.

Dietary intake of methyl donors, such as folic acid and methionine, shows considerable intra-individual variation in human populations. While it is recognized that maternal departures from the optimum of dietary methyl donor intake can increase the risk for mental health issues and neurological disorders in offspring, it has not been explored whether paternal dietary methyl donor intake influences behavioral and cognitive functions in the next generation. Here, we report that elevated paternal dietary methyl donor intake in a mouse model, transiently applied prior to mating, resulted in offspring animals (methyl donor-rich diet (MD) F1 mice) with deficits in hippocampus-dependent learning and memory, impaired hippocampal synaptic plasticity and reduced hippocampal theta oscillations. Gene expression analyses revealed altered expression of the methionine adenosyltransferase Mat2a and BK channel subunit Kcnmb2, which was associated with changes in Kcnmb2 promoter methylation in MD F1 mice. Hippocampal overexpression of Kcnmb2 in MD F1 mice ameliorated altered spatial learning and memory, supporting a role of this BK channel subunit in the MD F1 behavioral phenotype. Behavioral and gene expression changes did not extend into the F2 offspring generation. Together, our data indicate that paternal dietary factors influence cognitive and neural functions in the offspring generation.

Review on flower-visiting behaviour of orthopterans and setting priorities for further studies.

The importance of pollination and pollinators is easy to underestimate and impossible to overstate, since its importance goes far beyond the crop production and even the maintenance of plant populations. Most terrestrial ecosystems ultimately depend on the plant-pollinator interactions formed by million years coevolution. This is essential for both the daily functioning of the ecosystems and the long-term development of biodiversity. At the same time, the loss of biodiversity caused by climate change and human activities will soon lead to an ecological crisis, a catastrophe, which could endanger our life: For example, through the decline and loss of various ecosystem services. Such may be the pollination crisis, resulted from a significant loss of pollinating insects' diversity and abundance. The discovery of a pollinator Orthoptera species has encouraged researchers in the densely populated region of Indo-Malaysia to explore the potential role of orthopterans as pollinators. Although the flower visitation of some species has been already known, the role of orthopterans in pollination is scarcely revealed. Here, we collected and reviewed the available data in order to point out some factors of their importance and set priorities that may serve as a basis for further investigations regarding ecological, evolutionary and practical points of view.

Setting priorities and evaluation of habitats for the conservation of orthopterans: case study in the Aggtelek National Park (N Hungary).

The biodiversity conservation needs recent high-quality data and efficient methods for prioritizing species and sites for conservation. Here we prioritized Orthoptera habitats of the Aggtelek National Park, based on revised and actualized distribution data of 69 Orthoptera species living at 98 sites. The simple ranking and complementary areas methods were used with species richness (S), rarity weighted species richness (SR), and number of rare species (SQ). Additionally, the Grasshopper Conservation Indexes (GCI" and GCIn") combining European and local rarity and dispersal capacity of the species were also tested. Contrary to simple ranking the complementary areas method represented the whole fauna and significant part of the species-site data records. All the used indices performed similar except the standardized GCIn" which is highly affected by the differences in study intensity of sites. High-priority areas of the Aggtelek National Park were designated in the plateau above Jósvafo and Aggtelek villages and in the small, isolated hill near Jósvafo (Szolo-hegy) covered with remained mosaic of former vineyards, orchards and hayfields. The combined use of the efficient indices provides additional ranking that allows the best selection of hotspots to support efficient use of limited resources in nature conservation.

European Society of Gastrointestinal Endoscopy, European Society of Gastroenterology and Endoscopy Nurses and Associates, and the European Society of Anaesthesiology Guideline: Non-anesthesiologist administration of propofol for GI endoscopy.

Propofol sedation by non-anesthesiologists is an upcoming sedation regimen in several countries throughout Europe. Numerous studies have shown the efficacy and safety of this sedation regimen in gastrointestinal endoscopy. Nevertheless, this issue remains highly controversial. The aim of this evidence- and consensus-based set of guideline is to provide non-anesthesiologists with a comprehensive framework for propofol sedation during digestive endoscopy. This guideline results from a collaborative effort from representatives of the European Society of Gastrointestinal Endoscopy (ESGE), the European Society of Gastroenterology and Endoscopy Nurses and Associates (ESGENA) and the European Society of Anaesthesiology (ESA). These three societies have endorsed the present guideline.

European Society of Gastrointestinal Endoscopy, European Society of Gastroenterology and Endoscopy Nurses and Associates, and the European Society of Anaesthesiology Guideline: Non-anaesthesiologist administration of propofol for GI endoscopy.

Propofol sedation by non-anaesthesiologists is an upcoming sedation regimen in several countries throughout Europe. Numerous studies have shown the efficacy and safety of this sedation regimen in gastrointestinal endoscopy. Nevertheless, this issue remains highly controversial. The aim of this evidence- and consensus-based set of guideline is to provide non-anaesthesiologists with a comprehensive framework for propofol sedation during digestive endoscopy. This guideline results from a collaborative effort from representatives of the European Society of Gastrointestinal Endoscopy (ESGE), the European Society of Gastroenterology and Endoscopy Nurses and Associates (ESGENA) and the European Society of Anaesthesiology (ESA). These three societies have endorsed the present guideline.The guideline is published simultaneously in the Journals Endoscopy and European Journal of Anaesthesiology.

Once daily versus three times daily mesalazine granules in active ulcerative colitis: a double-blind, double-dummy, randomised, non-inferiority trial.

OBJECTIVES: To determine the therapeutic equivalence and safety of once daily (OD) versus three times daily (TID) dosing of a total daily dose of 3 g Salofalk (mesalazine) granules in patients with active ulcerative colitis. DESIGN: A randomised, double-blind, double-dummy, parallel group, multicentre, international, phase III non-inferiority study. SETTING: 54 centres in 13 countries. PATIENTS: 380 patients with confirmed diagnosis of established or first attack of ulcerative colitis (clinical activity index (CAI)>4 and endoscopic index > or =4 at baseline) were randomised and treated. INTERVENTIONS: 8-week treatment with either 3 g OD or 1 g TID mesalazine granules. MAIN OUTCOME MEASURES: Clinical remission (CAI< or =4) at study end. RESULTS: 380 patients were evaluable for efficacy and safety by intention-to-treat (ITT); 345 for per protocol (PP) analysis. In the ITT population, 79.1% in the OD group (n = 191) and 75.7% in the TID group (n = 189) achieved clinical remission (p<0.0001 for non-inferiority). Significantly more patients with proctosigmoiditis achieved clinical remission in the OD group (86%; n = 97) versus the TID group (73%; n = 100; p = 0.0298). About 70% of patients in both treatment groups achieved endoscopic remission, and 35% in the OD group and 41% in the TID group achieved histological remission. About 80% of all patients preferred OD dosing. Similar numbers of adverse events occurred in 55 patients (28.8%) in the OD group and in 61 patients (32.3%) in the TID group, indicating that the two dosing regimens were equally safe and well tolerated. CONCLUSIONS: OD 3 g mesalazine granules are as effective and safe as a TID 1 g schedule. With respect to the best possible adherence of patients to the treatment, OD dosing of mesalazine should be the preferred application mode in active ulcerative colitis.

Ischemia reperfusion injury of the skeletal muscle after selective deafferentation.

The present study analyzes the effect of selective deafferentation on the reperfusion injury of the skeletal muscle when nociceptive sensory fibers of the left sciatic nerve are selectively damaged by capsaicin pretreatment in a rat model following tourniquet ischemia (ISC) applied for 30 min, 1 h, and 2 h on the left hind limb. The isometric tetanic contractile force of the extensor digitorum longus (EDL) muscle was measured after 1 h, and 1, 3, or 7 days of reperfusion. Contractile force of the damaged muscle was compared to the intact contralateral muscle. In another group, ISC was used without capsaicin pre-treatment. After 30 min of ISC, there was no difference between deafferented and non-pretreated groups. Following 1 h ISC, with the exception of 1 h reperfusion, the non-pretreated group produced stronger contractions than the deafferented group. After 2 h ISC, the contractile force of the deafferented muscle was significantly stronger compared to the non-deafferented muscle force at all reperfusion times. In conclusions, it was found that the absence of peptidergic sensory fibers after long-lasting (2 h) ischemia is beneficial in reperfusion injury, whereas the absence of vasodilator peptides has unfavorable effects if tissue damage is milder (after 1 h ischemia).

Eradication of Helicobacter pylori has no effect on gastric acidity in duodenal ulcer patients--evaluation of 24-h pH monitoring.

It is accepted that eradication of Helicobacter pylori leads to healing of chronic active gastritis facilitates ulcer healing and prevents ulcer recurrence in duodenal ulcer (DU) patients. However, it is not entirely known whether the eradication of the bacteria normalizes gastric acid secretion and abolishes dyspeptic symptoms after ulcer healing. This study was aimed to evaluate the intragastric acidity and dyspeptic complaints before, and 3 months after, eradication in 18 endoscopically proven H. pylori positive DU patients. Gastric pH was measured by 24-h continuous intraluminal recording, serum gastrin measurements and Congo-red tests were also performed. Dyspeptic complaints and antacid consumptions were recorded in diary cards, antisecretory therapy was not allowed after the cessation of eradication therapy. Endoscopy, H. pylori status and Congo-red tests were controlled at the 6th and 12th week, while pH measurements and serum gastrin tests were performed at inclusion and 3 months later. Three patients dropped out and in 14 out of the remaining subjects healing of DUs and successful eradication was achieved by the 6th and 12th week controls. The 24-h median pH and the percentage of 24-h pH readings under pH 3 were not changing significantly by the 3-month controls (from 1.9+/-0.5 to 1.8+/-0.4 and from 52.6+/-5.5% to 58.6+/-5%, respectively). Similarly, no significant changes were observed in serum gastrin levels and dyspeptic symptom scores (from 72+/-7 pg/ml to 56.7+/-8 pg/ml and from 2.69+/-0.4 to 1.26+/-0.3, respectively). The antacid consumption was almost stable when compared with the pre- and post-eradication periods. It was concluded that despite successful H. pylori eradication and healing of DU, intragastric acidity does not change significantly at least 3 months after the therapy. The persisting dyspeptic symptoms and the need for antacid consumption suggest that some healed ulcer patients require antisecretory therapy in the post-eradication period.

Leukocyte mobilization, chemiluminescence response, and antioxidative capacity of the blood in intestinal ischemia and reperfusion.

Intestinal ischemia and reperfusion elicits changes in leukocyte counts and increased production of reactive oxygen species (ROS). The purpose of this study was to investigate whether these changes were followed by and/or connected with changes in the extracellular antioxidative capacity in a rat superior mesenteric artery (SMA) occlusion/reperfusion model. The SMA was occluded for 45 min and then allowed to be reperfused. Changes of leukocyte, polymorphonuclear (PMN), and lymphocyte counts, chemiluminescence (CL) of whole blood samples as a marker of ROS production, and the total antioxidative capacity of the serum were quantified at the end of ischemia and in 1 h intervals during the postischemic period up to 4 h. The myeloperoxidase (MPO) activity in the serum and intestinal tissue samples was also determined. The MPO activity in the intestinal tissue samples was significantly elevated at the end of ischemia, and this elevation lasted for the whole postischemic period. The oxidative challenge to the body induced a fast mobilization of extracellular antioxidative mechanisms already at the end of ischemia, which was followed by a significant increase in PMN counts and whole blood CL starting at the 2nd hour after reperfusion. The increased CL activity of whole blood was attributed to the increase of the circulating PMNs. No significant changes were observed in leukocyte and lymphocyte counts. It is concluded that compensatory mechanisms of the oxidative-antioxidative balance of the body react very quickly if challenged.

A new method for high-performance liquid chromatographic determination of drotaverine in plasma.

A sensitive, specific high-performance liquid chromatographic procedure was developed for the determination of plasma drotaverine levels. Basic plasma samples were adjusted to pH 1.5 and extracted with chloroform. HPLC [n-heptane-dichloromethane-diethylamine (50:25:2)] on a microporous silica column, with a variable-wavelength UV detector set at 302 nm allowed the measurement of drotaverine at the 50-ng/mL level. The utility of this method for determination of drotaverine in dog and rat plasma was demonstrated.

Influence of chlorhexidine species on the liquid crystalline structure of vehicle.

The aim of this study was to investigate the influence of three chlorhexidine species, chlorhexidine base and its salts (diacetate and digluconate), on the physico-chemical features of liquid crystalline systems and on drug transport through lipophilic membranes. Nonionic surfactant, Synperonic A7 (PEG(7)-C(13--15)) was selected for the preparation of the liquid crystalline systems. Mixtures of different ratios of Synperonic A7 and water were prepared. The liquid crystalline systems were characterized using polarizing microscopy, small-angle neutron scattering and transmission electron microscopy. Membrane transport was also examined. The addition of chlorhexidine species to the liquid crystalline system modified the structure of the liquid crystalline system. As a result of liquid crystal--drug interaction, the solubility of chlorhexidine base and its diffusion through lipophilic membranes increased in comparison with those of the chlorhexidine salts.

Effect of plasticizer on the dynamic surface tension and the free volume of Eudragit systems.

The purpose of the present study was to determine the changes of dynamic surface tension of aqueous Eudragit dispersions quantitatively and compare these data with the free volume of the free films formed from several dispersions of different dibutyl sebacate (DBS) concentrations. Eudragit L 30D and Eudragit RL 30D aqueous colloidal polymer dispersions and their cast free films were examined. The concentration of DBS varied in the dispersions from 0 to 20%. The dynamic surface tension of the dispersions were measured by the Du Nouy ring method while the free volume of cast films were determined by positron annihilation spectroscopy. The obtained results show that dynamic surface tension measurements indicate the white point (WP) of Eudragit dispersions by a significant standard deviation increase. This may suggest the applicability of dynamic surface tension measurements for the determination of the WP of polymeric dispersions. A decrease in the WP temperature of Eudragit dispersions with an increasing plasticizer concentration was observed up to the DBS concentration of 10% w/w. Above this concentration neither the WP of the polymer dispersion nor the free volume of the free films of the polymer were changed remarkably.

The effect of liquid crystalline structure on chlorhexidine diacetate release.

The aim of this study was to examine different liquid crystalline preparations containing chlorhexidine diacetate and to find connection between their structure and the kinetic of drug release. Nonionic surfactant, Synperonic A7 (PEG(7)-C(13-15)) was selected for the preparation of the examined liquid crystalline systems. Mixtures of different ratios of Synperonic A7 and water were produced. By increasing the water content of the systems, lamellar and hexagonal liquid crystal structures were observed. For the analysis of the prepared liquid crystalline systems polarising microscopy, rheology study, differential scanning calorimetry and dynamic swelling tests were carried out. The chlorhexidine diacetate release was examined by Franz-type vertical diffusion cell apparatus. The chlorhexidine diacetate release from hexagonal liquid crystalline preparations was characterised by zero-order release kinetics, while the drug release from lamellar liquid crystalline systems was described by anomalous (non-Fickian) transport. The results indicate that the drug release kinetic is strongly dependent on the liquid crystalline structure.

Contribution to the methodology of optimization and in-process control of some physical properties of pharmaceutical bulk substances and granulates.

Many experts consider drug analysis exclusively as a chemical measuring technique. In the pharmaceutical industry, physical and physico-chemical parameters form an integrated part of the quality specification, because they play an essential role both in quality assurance and in the technical and economic aspects of production on the commercial scale. Such physical and physico-chemical properties are analysed by special, non-chemical methods. In their programme of systematic research in this field, the authors have elaborated new methods to test some essential properties of powders and granulates used in the production of compressed tablets. The following test and production methods have been developed: (i) the determination of flowing-sliding characteristics of granulates based on the measurement of the mass-flow (g s(-1)) and mass-flow density (g s(-1) cm(-2)); (ii) the determination of optimum granulometric parameters with regard to tablet diameter; (iii) the direct determination of the temperature-dependent equilibrium vapour pressure; and (iv) the compression of tablets under controlled temperature.

Effect of particle size and coating level on the diffuse reflectance of wax matrices.

The aim of this study was to examine the influence of particle size and extent of coating on the diffuse-reflectance spectra of wax matrices containing embedded potassium chloride. Near-infrared spectroscopy was used to analyse the diffuse-reflectance characteristics of the prepared multi-particulate matrices without destructive sample preparation. A 2-factor, 3-level face-centred central composite design was selected to construct a second-order polynomial model which described the effect of particle size and amount of coating on the intensity of the diffusely reflected light. A non-linear model was used to demonstrate the effect of the selected parameters on the intensity of the reflected light; good correlation was obtained between experimental and predicted results. The results indicated that the extent of coating and the particle size of the examined systems in the selected particle size-range modified the intensity of the reflected light. It can be concluded that near-infrared spectroscopy is a sensitive means of measuring not only the particle size of powders (substrates and their mixtures), but also that of coated multi-particulate systems.

Time course of leukocyte response and free radical release in an early reperfusion injury of the superior mesenteric artery.

The sequence of changes in circulating immune cells and in free radical production was studied during the small intestine reperfusion. Rat small intestine ischemia/reperfusion was induced by a 45 min superior mesenteric artery occlusion followed by a 4-hour reperfusion. Samples of peripheral blood were collected every 20 min during reperfusion. While the number of polymorphonuclear leukocytes increased significantly both in the sham-operated controls and the experimental group (about 400 per cent at the end of reperfusion), a decrease in lymphocyte counts to 60 per cent was observed in the experimental group only. Although there were no changes in the counts of total T lymphocytes, a significant reduction in B cell counts was observed. Flow-cytometrical measurements showed no changes in the Tc subpopulation, while the Th subpopulation increased in the experimental group only. Free radical generation in blood (luminometric measurements) increased gradually and reached an eight-fold level by the end of reperfusion in both groups. Thus, it has been shown that the increase in free radical production is mainly due to the increased number of polymorphonuclear leukocytes mobilized already at the initial stages of reperfusion. The reduction in B lymphocyte population is probably due to homing mechanisms

A controlled multicentre therapeutic trial to determine the efficacy of a novel antacid (AI-Mg-hydroxy-carbonate) in duodenal ulcer.

Tisacid (a new, modern Hungarian AI-containing antacid) with a high acid-neutralizing capacity (greater than 26.8 mmol/g) also enhances gastric mucosal defense mechanisms (prostaglandin-dependent gastroprotection). A simple-blind, prospective, randomized, parallel multicentre clinical trial has been performed on both the clinical efficacy and possible side-effects of Tisacid monotherapy (AI-Mg-hydroxy-carbonate) on informed patients suffering from active duodenal ulcers. The four study groups were as follows: Group A: 3 g/day of Tisacid (acid-neutralizing capacity = 78 mmol, n = 85), Group B: 6 g/day of Tisacid (acid-neutralizing capacity = 156 mmol, n = 88), Group C: 12 g/day of Tisacid (acid-neutralizing capacity = 312 mmol, n = 68), Group D (as control): 1.0 g/day cimetidine (n = 91). The total number of patients was 332. It was found that the new Hungarian antacid compound (both tablet and suspension) can essentially accelerate the healing rate of duodenal ulcers; the cumulative healing rate of ulcers and the decrease of complaints can be achieved equally by relatively low doses of Tisacid monotherapy and cimetidine alone; and there were no essential differences between the clinical potency and side-effects of Tisacid tablets or the suspension.

Actinic granuloma in alcoholic liver disease.

Actinic granuloma is a rare condition. Its acceptance as a defined disease has been queried several times. The authors observed a classic case in a patient with alcoholic cirrhosis of the liver and diabetes. The possible role of metabolic disturbances in the pathogenesis of this syndrome is reviewed.

Intraspecific invariability of the internal transcribed spacer region of rDNA of the truffle Terfezia terfezioides in Europe.

ITS regions (internal transcribed spacers--ITS1 and ITS2--with the 5.8S gene of the nuclear rDNA) of 25 fruit body samples of Terfezia terfezioides, originating from Hungary and Italy, were compared. The amplification and sequencing of the ITS region was successful with both the ITS1-ITS4 and ITS1F-ITS4 primer pairs. No differences of the restriction fragment length polymorphism profiles were detected among 19 samples collected in one place at the same time. The sequences of the ITS region of 9 samples collected in different localities were highly invariable, differing in only two bases. Thus the intraspecific homogeneity of the ITS region seems to be an important species-specific characteristic of T. terfezioides in contrast to other Terfezia species. As the samples of the species were collected from different and distant localities of Europe, the ITS sequence of T. terfezioides can be considered a very conservative, reliable molecular marker of the fungus.