Polyphenol Content and Antioxidant Activity of Sour Cherries From Serbia

The aim of this study was to evaluate the content of phenolics: the total phenols (TP), flavonoids (TF), anthocyanins (TA), as well as the total antioxidant\ud capacity (TAC) in three sour cherry cultivars (Prunus cerasus L.) introduced to the southeast Serbia climate conditions. Among the investigated sour cherries,\ud „Oblačinska“ cultivar contained the highest amounts of all groups of phenolics, followed by „Cigančica“ > „Marela“. A significant difference were observed in the phenolic content among different cultivars and growing seasons (p  0.05), and the phenolic compounds were significantly higher in the growing season 2009. The examined cultivars possess a high antioxidant capacity, and all phenolics of highy correlation with TAC. The following compounds were identified and quantified using HPLC-DAD: 4 anthocyanins, the most abundant of which was cyanidin-3-glucoside in “Marela” and “Oblačinska”, and cyanidin-3-glucosylrutinoside in „Cigančica“, and 4 hydroxycinnamic acids, the most abundant of which was neochlorogenic acid in all sour cherry cultivars. The growing and ripening process on the tree of sour cherry cv. „Oblačinska“ was evaluated also. The results showed significant increases in total phenols during the ripening, the total anthocyanins and total antioxidant capacity and 4 quantified anthocyanins, however the neochlorogenic acid decreased during the ripening. The study indicated that the growing and climate conditions in southeast Serbia are convenient for introducing sour cherry cultivars.\u

Fast and Accurate Power Estimation of FPGA DSP Components Based on High-level Switching Activity Models

When designing DSP circuits, it is important to predict their power consumption early in the design flow in order to reduce the repetition of time consuming design phases. High-level modelling is required for fast power estimation when a design is modified at the algorithm level. This paper presents a novel high-level analytical approach to estimate logic power consumption of arithmetic components implemented in FPGAs. In particular, models of adders and multipliers are presented in detail. The proposed methodology considers input signal correlation and glitching produced inside the component. It is based on an analytical computation of the switching activity in the component which takes into account the component architecture. The complete model can estimate the power consumption for any given clock frequency, signal statistics and operands’ word-lengths. Compared to other proposed power estimation methods, the number of circuit simulations needed for characterizing the power model of the component is highly reduced. The accuracy of the model is within 10% of low-level power estimates given by the tool XPower, and it achieves better overall performance

The hVPS34-SGK3 pathway counteracts inhibition of the PI3K-Akt to maintain mTORC1 and tumour growth

We explore mechanisms that enable cancer cells to tolerate PI3K or Akt inhibitors. Prolonged treatment of breast cancer cells with PI3K or Akt inhibitors leads to increased expression and activation of a kinase termed SGK3 that is related to Akt. Under these conditions, SGK3 is controlled by hVps34 that generates PtdIns(3)P, which binds to the PX domain of SGK3 promoting phosphorylation and activation by its upstream PDK1 activator. Furthermore, under conditions of prolonged PI3K/Akt pathway inhibition, SGK3 substitutes for Akt by phosphorylating TSC2 to activate mTORC1. We characterise 14h, a compound that inhibits both SGK3 activity and activation in vivo, and show that a combination of Akt and SGK inhibitors induced marked regression of BT‐474 breast cancer cell‐derived tumours in a xenograft model. Finally, we present the kinome‐wide analysis of mRNA expression dynamics induced by PI3K/Akt inhibition. Our findings highlight the importance of the hVps34‐SGK3 pathway and suggest it represents a mechanism to counteract inhibition of PI3K/Akt signalling. The data support the potential of targeting both Akt and SGK as a cancer therapeutic

Supersaturated lipid-based drug delivery systems–exploring impact of lipid composition type and drug properties on supersaturability and physical stability

Objective: The objective of the current study was to systematically investigate the impact of lipid composition on the ability to design supersaturated lipid-based drug delivery systems (sLBDDS) using three model drugs with different physico-chemical properties. Significance: This study expands the list of investigated sLBDDS by using alternative vehicle compositions relative to current literature. Methods & Results: Drug supersaturation was thermally-induced based on previously reported methods and was successfully achieved for celecoxib and cinnarizine. For the novel drug, JNJ-2A, a lower supersaturation potential was observed for the tested LBDDS. For celecoxib and cinnarizine, crystalline precipitate was observed for some sLBDDS upon storage at 25 °C/65%RH, particularly for medium chain sLBDDS (celecoxib) and long chain sLBDDS (cinnarizine). The greater risk of precipitation observed for celecoxib and cinnarizine, particularly at higher apparent degree of supersaturation (aDS) may be related to their higher crystallization tendency as determined by differential scanning calorimetry. Conclusions: In conclusion, the potential for supersaturation in LBDDS, and the risk of precipitation, was found to be highly drug dependent. The apparent degree of supersaturation was considered a major factor impacting the ability to maintain drug supersaturation upon storage

Standard lumbar discectomy versus microdiscectomy - Differences in clinical outcome and reoperation rate

Microdiscectomy (MD) is accepted nowadays as the operative method of choice for lumbar disc herniation, but it is not rare for neurosurgeons to opt for standard discectomy (SD), which does not entail the use of operating microscope. In our study, diff erences in disc herniation recurrence and clinical outcome of surgical treatment of lumbar disc herniation with and without the use of operating microscope were assessed. Our study included 167 patients undergoing lumbar disc surgery during a three-year period (SD, n=111 and MD, n=56). Clinical outcome assessments were recorded by patients via questionnaire forms filled out by patients at three time points. Operation duration, length of hospital stay and revision surgeries were also recorded. According to study results, after one-year follow up there was no statistically significant diff erence between the SD and MD groups in functional outcome. However, we recorded a statistically significant diff erence in leg pain reduction in favor of the MD group. According to the frequency of reoperations with the mean follow up period of 33.4 months, there was a statistically significant diff erence in favor of the MD group (SD 6.3% vs. MD 3.2%). There appears to be no particular advantage of either technique in terms of functional outcome since both result in good overall outcome. However, we choose MD over SD because it includes significantly lower recurrent disc herniation rate and higher reduction of leg pain

Toward simplified oral lipid-based drug delivery using mono-/di-glycerides as single component excipients

Objective: This study aimed to systematically explore compositional effects for a series of lipid systems, on the in vitro drug solubilization and in vivo bioavailability of three poorly water-soluble drugs with different physico-chemical properties. Significance: While many lipid-based drug products have successfully reached the market, there is still a level of uncertainty on the design guidelines for such drug products with limited understanding on the influence of composition on in vitro and in vivo performance. Methods and Results: Lipid-based drug delivery systems were prepared using either single excipient systems based on partially digested triglycerides (i.e. mono- and/or di-glycerides) or increasingly complex systems by incorporating surfactants and/or triglycerides. These lipid systems were evaluated for both in vitro and in vivo behavior. Results indicated that simple single component long chain lipid systems are more beneficial for the absorption of the weak acid celecoxib and the weak base cinnarizine compared to equivalent single component medium chain lipid systems. Similarly, a two-component system produced by incorporating small amount of hydrophilic surfactant yields similar overall pharmacokinetic effects. The lipid drug delivery systems based on medium chain lipid excipients improved the in vivo exposure of the neutral drug JNJ-2A. The higher in vivo bioavailability of long chain lipid systems compared to medium chain lipid systems was in agreement with in vitro dilution and dispersion studies for celecoxib and cinnarizine. Conclusions: The present study demonstrated the benefits of using mono-/di-glycerides as single component excipients in LBDDS to streamline formulation screening and improve oral bioavailability for the three tested poorly water-soluble drugs

Exploring impact of supersaturated lipid-based drug delivery systems of celecoxib on in vitro permeation across Permeapad^Ⓡ membrane and in vivo absorption

Supersaturated lipid-based drug delivery systems have recently been investigated for oral administration for a variety of lipophilic drugs and have shown either equivalent or superior oral bioavailability compared to conventional non-supersaturated lipid-based drug delivery systems. The aim of the present work was to explore supersaturated versus non-supersaturated lipid-based systems at equivalent lipid doses, on in vivo bioavailability in rats and on in vitro permeation across a biomimetic PermeapadⓇ membrane to establish a potential in vivo - in vitro correlation. A secondary objective was to investigate the influence of lipid composition on in vitro and in vivo performance of lipid systems. Results obtained indicated that increasing the celecoxib load in the lipid-based formulations by thermally-induced supersaturation resulted in increased bioavailability for medium and long chain mono-/di-glycerides systems relative to their non-supersaturated (i.e. 85%) reference formulations, albeit only significant for the medium chain systems. Long chain systems displayed higher celecoxib bioavailability than equivalent medium chain systems, both at supersaturated and non-supersaturated drug loads. In vitro passive permeation of celecoxib was studied using both steady-state and dynamic conditions and correlated well with in vivo pharmacokinetic results with respect to compositional effects. In contrast, permeation studies indicated that flux and percentage permeated of supersaturated systems, either at steady-state or under dynamic conditions, decreased or were unchanged relative to non-supersaturated systems. This study has shown that by using two cell-free PermeapadⓇ permeation models coupled with rat-adapted gastro-intestinal conditions, bio-predictive in vitro tools can be developed to be reflective of in vivo scenarios. With further optimization, such models could be successfully used in pharmaceutical industry settings to rapidly screen various prototype formulations prior to animal studies