Diarylheptanoids from Green Alder Bark and Their Potential for DNA Protection

Nine diarylheptanoids, 1 – 9 , catechin ( 11 ), and a phenolic glucoside, 10 , were isolated from the bark of green alder (Alnus viridis). Four of the isolated compounds, i.e., 2, 5, 8, 10 , are new. The structures of 1 – 11 were determined on the basis of spectroscopic data. All isolated compounds were evaluated for their in vitro protective effects on chromosome aberrations in peripheral human lymphocytes using cytokinesis‐block micronucleus (CBMN) assay. Almost all of them exerted a pronounced effect of decreasing DNA damage of human lymphocytes, acting stronger than the known synthetic protector amifostine.     

Naturally occurring compounds in differentiation based therapy of cancer

Differentiation of cancer cells entails the reversion of phenotype from malignant to the original. The conversion to cell type characteristic for another tissue is named transdifferentiation. Differentiation/transdifferentiation of malignant cells in high grade tumor mass could serve as a nonaggressive approach that potentially limits tumor progression and augments chemosensitivity. While this therapeutic strategy is already being used for treatment of hematological cancers, its feasibility for solid malignancies is still debated. We will presently discuss the natural compounds that show these properties, with focus on anthraquinones from Aloe vera, Senna, Rheum sp. and hop derived prenylflavonoids.     

Isolation,characterization and evaluation of significant mycoflora and mycotoxins in pig feed from Serbian farms

This paper provides a brief review of approaches for the early detection and prevention strategies which have been employed in Serbia for the control of ochratoxogenic fungi and its metabolites in feed in the context of a hazard analysis critical control point (HACCP) framework. During a mycological analysis of complete feedmixes intended for fattening swine (n = 18), a total of six genera and 14 species of moulds were identified. Penicillium was present in considerably more samples than any other genus (94.4%), followed by the genera Fusarium (55.5%) and Paecilomyces (44.4%). Other fungi from the genera Aspergillus (22%), Mucor (11.1%) and Alternaria (5.5%) were represented in a smaller amount. Total fungal counts ranged from 10⁵ to 40 × 10⁵ c.f.u./g. The mycotoxins deoxynivalenol, ochratoxin A and zearalenone were detected, while aflatoxins were not present. Deoxynivalenol was detected in 10 samples in the concentration range 0.25–2.5 mg/kg. Ochratoxin A and zaralenone were detected in nine and eight samples, respectively, in the concentration range 0.057–0.27 and 0.2–5.0 mg/kg, respectively. Isolates identified as Aspergillus and Penicillium species were subjected to molecular characterization for the presence of genes responsible for the synthesis of OTA (polyketide synthase gene-PKS) using polymerase chain reaction (PCR) applied to a set of 18 isolates. The sequences of PCR reaction products in three samples were compared with nucleotide sequences of genes for polyketide synthase (PKS) from Penicillium species and it was found that the samples possessed the PKS sequence. These findings indicate that there may be a risk of animal exposure to mycotoxins through the consumption of mouldy infected feeds.     

The golden jackal (<Emphasis Type="Italic">Canis aureus</Emphasis>) in Bosnia and Herzegovina: density of territorial groups,population trend and distribution range

In this article, we present the results of the first systematic surveys of golden jackals in Bosnia and Herzegovina (B&H). The population status and distribution of the golden jackal (Canis aureus) in B&H was largely unknown, and the few existing literature records mention their presence at only five localities in the country. We interviewed managers of all the hunting grounds in B&H and reviewed available jackal hunting records from 2000 to 2016. In total, we collected 212 records of legally harvested jackals. We observed an increasing trend of harvested jackals in B&H (on average 35% annual increase) during this same period. Using the acoustic (playback) method, we confirmed the presence of 80 territorial jackal groups along six transects covering 3081 km². We estimated density to be a minimum of 0.33 groups/10 km² in northern B&H and 0.10 groups/10 km² in central B&H. Jackal groups were located at significantly lower altitudes with respect to available area along the transects. We present a distribution map of confirmed jackal occurrences in B&H, which indicates that the core area of jackal distribution in the country is currently located along the Sava River and its tributaries in the northern part of B&H. Jackals are sporadically present in the rest of the country, where gray wolves (Canis lupus) probably limit their presence. In total, jackal presence has been detected in 19% (109 out of 586) of 10?×?10 km grid cells covering the country. The primary factor driving the expanding population of jackals in northern B&H appears to be immigration of jackals from Croatia and Serbia.     

Self-Medication Practices and Risk Factors for Self-Medication among Medical Students in Belgrade,Serbia

Introduction

Self-medication among future health care professionals can represent a serious threat to professionalism in medicine and it has potential to put at risk public trust into this profession. The aim of this research was to investigate prevalence and risk factors for self-medication among population of medical students, because it was previously shown that their attitudes towards pharmacotherapy could affect the way they could prescribe medication in the future.

Material and Methods

Research was performed as a cross-sectional study and it included 1296 (84.1%) 1st, 3rd and 6th year students of School of Medicine, University of Belgrade. Students filled out a demographic and self-medication questionnaire created for the purpose of this research and the Physical Health Questionnaire – 9 (PHQ-9). Questions about self-medication were related to the period of the previous year.

Results

Self-medication was reported by 79.9% students. The most frequently self-prescribed medications were analgesics (55.4%). Independent risk factors for self-medication were possession of home-pharmacies (OR = 5.3, CI 95% 3.89–7.23), lower level of father''s education (OR = 1.6, CI 95% 1.18–2.25), consumption of alcoholic beverages (OR = 1.5, CI 95% 1.13–2.08), less than 1 hour spent in physical activity per week (OR = 1.4, CI 95% 1.00–2.02), female gender (OR = 1.4, CI 95% 1.02–1.89), older age (OR = 1.1, CI 95% 1.07–1.21) and higher PHQ-9 score (OR = 1.09, CI 95% 1.05–1.12).

Conclusions

Self-medication is an important issue among population of medical students. Prevalence of self-medication could be controlled through regulatory authorities and further education.     

The activity of erythrocyte and brain Na+/K+ and Mg2+-ATPases in rats subjected to acute homocysteine and homocysteine thiolactone administration

Hyperhomocysteinemia is associated with various pathologies including cardiovascular disease, stroke, and cognitive dysfunctions. Systemic administration of homocysteine can trigger seizures in animals, and patients with homocystinuria suffer from epileptic seizures. Available data suggest that homocysteine can be harmful to human cells because of its metabolic conversion to homocysteine thiolactone, a reactive thioester. A number of reports have demonstrated a reduction of Na⁺/K⁺-ATPase activity in cerebral ischemia, epilepsy and neurodegeneration possibly associated with excitotoxic mechanisms. The aim of this study was to examine the in vivo effects of d,l-homocysteine and d,l-homocysteine thiolactone on Na⁺/K⁺- and Mg²⁺-ATPase activities in erythrocyte (RBC), brain cortex, hippocampus, and brain stem of adult male rats. Our results demonstrate a moderate inhibition of rat hippocampal Na⁺/K⁺-ATPase activity by d,l-homocysteine, which however expressed no effect on the activity of this enzyme in the cortex and brain stem. In contrast,d,l-homocysteine thiolactone strongly inhibited Na⁺/K⁺-ATPase activity in cortex, hippocampus and brain stem of rats. RBC Na⁺/K⁺-ATPase and Mg²⁺-ATPase activities were not affected by d,l-homocysteine, while d,l-homocysteine thiolactone inhibited only Na⁺/K⁺-ATPase activity. This study results show that homocysteine thiolactone significantly inhibits Na⁺/K⁺-ATPase activity in the cortex, hippocampus, and brain stem, which may contribute at least in part to the understanding of excitotoxic and convulsive properties of this substance.     

Tuning a Parallel Segmented Flow Column and Enabling Multiplexed Detection

Active flow technology (AFT) is new form of column technology that was designed to overcome flow heterogeneity to increase separation performance in terms of efficiency and sensitivity and to enable multiplexed detection. This form of AFT uses a parallel segmented flow (PSF) column. A PSF column outlet end-fitting consists of 2 or 4 ports, which can be multiplexed to connect up to 4 detectors. The PSF column not only allows a platform for multiplexed detection but also the combination of both destructive and non-destructive detectors, without additional dead volume tubing, simultaneously. The amount of flow through each port can also be adjusted through pressure management to suit the requirements of a specific detector(s). To achieve multiplexed detection using a PSF column there are a number of parameters which can be controlled to ensure optimal separation performance and quality of results; that is tube dimensions for each port, choice of port for each type of detector and flow adjustment. This protocol is intended to show how to use and tune a PSF column functioning in a multiplexed mode of detection.     

Compressive Stress Inhibits Proliferation in Tumor Spheroids through a Volume Limitation

In most instances, the growth of solid tumors occurs in constrained environments and requires a competition for space. A mechanical crosstalk can arise from this competition. In this article, we dissect the biomechanical sequence caused by a controlled compressive stress on multicellular spheroids (MCSs) used as a tumor model system. On timescales of minutes, we show that a compressive stress causes a reduction of the MCS volume, linked to a reduction of the cell volume in the core of the MCS. On timescales of hours, we observe a reversible induction of the proliferation inhibitor, p27^Kip1, from the center to the periphery of the spheroid. On timescales of days, we observe that cells are blocked in the cell cycle at the late G1 checkpoint, the restriction point. We show that the effect of pressure on the proliferation can be antagonized by silencing p27^Kip1. Finally, we quantify a clear correlation between the pressure-induced volume change and the growth rate of the spheroid. The compression-induced proliferation arrest that we studied is conserved for five cell lines, and is completely reversible. It demonstrates a generic crosstalk between mechanical stresses and the key players of cell cycle regulation. Our results suggest a role of volume change in the sensitivity to pressure, and that p27^Kip1 is strongly influenced by this change.     

Modulations of rabbit erythrocyte ATPase activities induced by in vitro and in vivo exposure to ethanol

Alcohol intake is associated with numerous degenerative disorders, and the detrimental effects of alcohol may be due to its influence on plasma membrane and cellular transport systems. The aim of the present study was to compare in vitro and in vivo effects of ethanol on rabbit erythrocyte ATPase activities and correlate them with ethanol-induced oxidative stress. Age-matched male rabbits were given 5% ethanol in 2% sucrose solution, for 6 weeks ad libitum; control animals were given tap water. Daily intake of ethanol was 5 g/kg body weight; this experimental regimen resulted in an average serum ethanol concentration of 16.77 ± 2.00 mM/l. After this period, blood was collected, serum ethanol concentration was determined and erythrocyte membranes were prepared according to the method of Post et al. Activities of Na⁺/K⁺- and Mg²⁺-ATPases were determined. Thiobarbituric acid-reactive substance (TBARS) assay was used to detect levels of lipid peroxidation, a major indicator of oxidative stress. In vitro ethanol inhibits both Na⁺/K⁺-ATPase and Mg²⁺-ATPase, but Na⁺/K⁺-ATPase is more sensitive to the ethanol-induced inhibition. Increasing concentration of ethanol increased TBARS production, but significant difference was attained only at 5 and 12.5 mM of ethanol. Chronic ethanol consumption induced significant increase in Na⁺/K⁺- and Mg²⁺-ATPase activity, and TBARS production. Our results suggest that increased ATPase activity induced by chronic ethanol consumption is due to oxidative, induced modification of membrane phospholipids and proteins, which are responsible for inhibition of ATPase activity. Increased production of TBARS induced by in vitro exposure to ethanol is not the only factor that influences ATPases activity. Further research is needed to elucidate this relationship.