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Open access

Faisal Al-Otaibi

Abstract

There are several limited approaches to treat epilepsy in hospitals, for example, using medicines, surgery, electrical stimulation and dietary interventions. Despite the availability of all these new and old approaches, seizure is particularly difficult to manage. The quest for new antiepileptic molecules with more specificity and less CNS toxicity continues for medicinal chemists until a new and ideal drug arrives. This review covers new antiseizure molecules of different chemical classes, the exact mode of action of which is still unidentified. Newer agents include sulfonamides, thiadiazoles, semi- and thiosemicarbazones, pyrrolidine-2,5-diones, imidazoles, benzothiazoles and amino acid deriva tives. These new chemical entities can be useful for the design and development of forthcoming antiseizure agents.

Open access

Karolina Słoczyńska, Agnieszka Gunia-Krzyżak, Paulina Koczurkiewicz, Katarzyna Wójcik-Pszczoła, Dorota Żelaszczyk, Justyna Popiół and Elżbieta Pękala

Abstract

Determination of metabolic profiles of new chemical entities is a key step in the process of drug discovery, since it influences pharmacokinetic characteristics of therapeutic compounds. One of the main challenges of medicinal chemistry is not only to design compounds demonstrating beneficial activity, but also molecules exhibiting favourable pharmacokinetic parameters. Chemical compounds can be divided into those which are metabolized relatively fast and those which undergo slow biotransformation. Rapid biotransformation reduces exposure to the maternal compound and may lead to the generation of active, non-active or toxic metabolites. In contrast, high metabolic stability may promote interactions between drugs and lead to parent compound toxicity. In the present paper, issues of compound metabolic stability will be discussed, with special emphasis on its significance, in vitro metabolic stability testing, dilemmas regarding in vitro-in vivo extrapolation of the results and some aspects relating to different preclinical species used in in vitro metabolic stability assessment of compounds.

Open access

Yufang Ni, Zhixian Cao and Qingquan Liu

Abstract

A 2D hydrodynamic (labeled as CAR) model has been proposed in a rectangular Cartesian coordinate system with two axes within the horizontal plane and one axis along the vertical direction (global coordinates), considering the effects of bed slope on both pressure distribution and bed shear stresses. The CAR model satisfactorily reproduces the analytical solutions of dam-break flow over a steep slope, while the traditional Saint-Venant Equations (labeled as SVE) significantly overestimate the flow velocity. For flood events with long duration and large mean slope, the CAR and the SVE models present distinguishable discrepancies. Therefore, the proposed CAR model is recommended for applications to real floods for its facility of extending from 1D to 2D version and ability to model shallow-water flows on steep slopes.

Open access

Rui Liu, Runze Yu, Yuxin Cui, Mengying Fan, Bo Wang and Yanmin Zhang

Abstract

The aim of this study was to investigate the inhibitory effect of TAD1822-7, a synthesized taspine derivative, on cancer through its effects on tumor cell growth and angiogenesis via suppression of EphrinB2. The obtained data showed that TAD1822-7 decreased Bel-7402 cell viability and colony formation ability and suppressed cell migration. TAD1822-7 effectively inhibited blood vessel formation in an aortic ring assay to examine angiogenesis. Moreover, it also down regulated the expression of VEGFR2, VEGFR3, CD34, PLCγ, Akt, MMP2, MMP9, and CXCR4, and suppressed the expression of EphrinB2 and its PDZ protein, PICK1, in Bel-7402 cells. These results indicate that TAD1822-7 is a potential anti-angiogenic agent that can inhibit the viability and migration of Bel-7402 cells via suppression of EphrinB2 and the related signaling pathways.

Open access

Jitka Kofroňová, Miroslav Tesař and Václav Šípek

Abstract

Longwave radiation, as part of the radiation balance, is one of the factors needed to estimate potential evapotranspiration (PET). Since the longwave radiation balance is rarely measured, many computational methods have been designed. In this study, we report on the difference between the observed longwave radiation balance and modelling results obtained using the two main procedures outlined in FAO24 (relying on the measured sunshine duration) and FAO56 (based on the measured solar radiation) manuals. The performance of these equations was evaluated in the April–October period over eight years at the Liz experimental catchment and grass surface in the Bohemian Forest (Czech Republic). The coefficients of both methods, which describe the influence of cloudiness factor and atmospheric emissivity of the air, were calibrated. The Penman-Monteith method was used to calculate the PET. The use of default coefficient values gave errors of 40–100 mm (FAO56) and 0–20 mm (FAO24) for the seasonal PET estimates (the PET was usually overestimated). Parameter calibration decreased the FAO56 error to less than 20 mm per season (FAO24 remained unaffected by the calibration). The FAO56 approach with calibrated coefficients proved to be more suitable for estimation of the longwave radiation balance.

Open access

Mohammad Reza Namaee and Jueyi Sui

Abstract

In the present study, experiments were conducted in a large-scale flume to investigate the issue of local scour around side-by-side bridge piers under both ice-covered and open flow conditions. Three non-uniform sediments were used in this experimental study. Analysis of armour layer in the scour holes around bridge piers was performed to inspect the grain size distribution curves and to study the impact of armour layer on scour depth. Assessments of grain size of deposition ridges at the downstream side of bridge piers have been conducted. Based on data collected in 108 experiments, the independent variables associated with maximum scour depth were assessed. Results indicate that the densi-metric Froude number was the most influential parameter on the maximum scour depth. With the increase in grain size of the armour layer, ice cover roughness and the densimetric Froude number, the maximum scour depth around bridge piers increases correspondingly. Equations have been developed to determine the maximum scour depth around bridge piers under both open flow and ice covered conditions.

Open access

Feliciana Licciardello, Salvatore Barbagallo and Francesc Gallart

Abstract

Increasing our understanding of the main processes acting in small Mediterranean catchments is essential to planning effective soil and water conservation practices in semi-arid areas. A monitoring program of a Sicilian catchment started in 1996 and ended in 2006. The factors driving the hydrological response for 170 events with runoff generation and 46 with sediment production were specified. The catchment response varied greatly over the year. Rainfall intensity was a poor driver of runoff generation, whereas both the simulations made with the Thornthwaite-Mather water balance model and hydrograph recession analyses, pointed to the chief importance of wet antecedent conditions and soil saturation processes in runoff generation. The influence of rainfall spatial variability was also examined. SSC-Q relationships, classified by following their shapes for all sediment production events, suggested that the principal role of small poorly vegetated hillslope patches was as sediment sources and confirmed the complexity of the hydrological response in this small Mediterranean catchment.

Open access

Corina Bubueanu, Rasit Iuksel and Minerva Panteli

Abstract

Lamium album and Lamium purpureum are species belonging to the genus Lamium. Aerial parts of the two species and roots of Lamium album have applications in human and veterinary traditional medicine. Haemostatic properties of butanolic extracts of Lamium species were investigated by two experimental models in Wistar rats: haemostatic test by tail bleeding time determination and acenocoumarolcarrageenan test. Results of the haemostatic test by tail bleeding determination demonstrated haemostatic activity of both extracts. In the acenocoumarol-carrageenan test, only the Lamium album extract showed haemostatic activity, comparable to that of vitamin K. Based on the qualitative chemical data on iridoid glycosides (HPTLC), 8-acetylshanzhiside methyl ester might be assumed to be responsible for haemostatic activity. Based on the acute toxicity test, none of the extracts showed toxicity.

Open access

Tanja Rozman Peterka, Tina Trdan Lušin, Jure Bergles, Zoran Ham, Rok Grahek and Uroš Urleb

Abstract

An ultra-high performance liquid chromatography method for simultaneous determination of tacrolimus impurities in pharmaceutical dosage forms has been developed. Appropriate chromatographic separation was achieved on a BEH C18 column using gradient elution with a total run time of 14 min. The method was applied to analyses of commercial samples and was validated in terms of linearity, precision, accuracy, sensitivity and specificity. It was found to be linear, precise and accurate in the range of 0.05 to 0.6 % of the impurities level in pharmaceutical dosage forms. Stability indicating power of the method was demonstrated by the results of forced degradation studies. The forced degradation study in solution revealed tacrolimus instability under stress alkaline, thermal, light and photolytic conditions and in the presence of a radical initiator or metal ions. The drug was stable at pH 3–5. Solid-state degradation studies conducted on amorphous tacrolimus demonstrated its sensitivity to light, elevated temperature, humidity and oxidation.

Open access

Markus C. Casper, Hadis Mohajerani, Sibylle Hassler, Tobias Herdel and Theresa Blume

Abstract

Evapotranspiration is often estimated by numerical simulation. However, to produce accurate simulations, these models usually require on-site measurements for parameterization or calibration. We have to make sure that the model realistically reproduces both, the temporal patterns of soil moisture and evapotranspiration. In this study, we combine three sources of information: (i) measurements of sap velocities; (ii) soil moisture; and (iii) expert knowledge on local runoff generation and water balance to define constraints for a “behavioral” forest stand water balance model. Aiming for a behavioral model, we adjusted soil moisture at saturation, bulk resistance parameters and the parameters of the water retention curve (WRC). We found that the shape of the WRC influences substantially the behavior of the simulation model. Here, only one model realization could be referred to as “behavioral”. All other realizations failed for a least one of our evaluation criteria: Not only transpiration and soil moisture are simulated consistently with our observations, but also total water balance and runoff generation processes. The introduction of a multi-criteria evaluation scheme for the detection of unrealistic outputs made it possible to identify a well performing parameter set. Our findings indicate that measurement of different fluxes and state variables instead of just one and expert knowledge concerning runoff generation facilitate the parameterization of a hydrological model.