Phosphorylation as a method of tuning the enantiodiscrimination potency of quinine--an NMR study

Quinines phosphorylated at the C-9 hydroxyl group (diphenyl and diethyl phosphates) were synthesized and validated as novel effective chiral solvating agents in two alternative methods based on (1)H and (31)P NMR spectroscopy. Tested with a representative set of racemic analytes, the title compounds induced shift nonequivalence effects in (1)H NMR signals with values up to 0.1-0.2 ppm for 3,5-dinitrobenzoyl-substituted amino acids. In terms of enantiodifferentiation extent and application range, introduction of a phosphate group was proven to be superior compared to the action of nonmodified quinine. Interestingly, a temperature decrease to reach the slow exchange conditions also produced nonequivalences in the (31)P NMR spectra of the selectors. Comprehensive NMR analysis showed the existence of two conformations (closed 1 and 2) for both quinines in their free forms and the open 3 arrangement for the protonated ones. The crystal structure of diethylphosphorylquinine hydrochloride dichloromethane hemisolvate revealed a similar conformation to that observed in solution. Structures of complexes of phosphorylated quinines with selected ligands were determined with the use of NMR-based molecular modeling studies.     

The effect of dietary zinc - and polyphenols intake on DMBA-induced mammary tumorigenesis in rats

Background

The aim of the study was to investigate the effect of dietary supplementation with zinc and polyphenol compounds, i.e. resveratrol and genistein, on the effectiveness of chemically induced mammary cancer and the changes in the content of selected elements (Zn, Cu, Mg, Fe, Ca) in tumors as compared with normal tissue of the mammary gland.

Methods

Female Sprague-Dawley rats were divided into study groups which, apart from the standard diet and DMBA (7,12-dimethyl-1,2- benz[a]anthracene), were treated with zinc ions (Zn) or zinc ions + resveratrol (Zn + resveratrol) or zinc ions + genistein (Zn + genistein) via gavage for a period from 40 days until 20 weeks of age. The ICP-OES (inductively coupled plasma optical emission spectrometry) technique was used to analyze the following elements: magnesium, iron, zinc and calcium. Copper content in samples was estimated in an atomic absorption spectrophotometer.

Results

Regardless of the diet (standard; Zn; Zn + resveratrol; Zn + genistein), DMBA-induced breast carcinogenesis was not inhibited. On the contrary, in the Zn + resveratrol supplemented group, tumorigenesis developed at a considerably faster rate. On the basis of quantitative analysis of selected elements we found - irrespectively of the diet applied - great accumulation of copper and iron, which are strongly prooxidative, with a simultaneous considerable decrease of the magnesium content in DMBA-induced mammary tumors. The combination of zinc supplementation with resveratrol resulted in particularly large differences in the amount of the investigated elements in tumors as compared with their content in normal tissue.

Conclusions

Diet supplementation with zinc and polyphenol compounds, i.e. resveratrol and genistein had no effect on the decreased copper level in tumor tissue and inhibited mammary carcinogenesis in the rat. Irrespectively of the applied diet, the development of the neoplastic process in rats resulted in changes of the iron and magnesium content in the cancerous tissue in comparison with the healthy mammary tissue. The application of combined diet supplementation with zinc ions and resveratrol considerably promoted the rate of carcinogenesis and increased the number of DMBA-induced mammary tumors.     

Anatomy of the coracoid and diversity of the Procellariiformes (Aves) in the Oligocene of Europe

Abstract: Two European species of the Diomedeoididae, an extinct family of procellariiform (tube‐nose) birds, have hitherto been distinguished primarily by size of their limb bones. Here, we describe an Early Oligocene (Rupelian) procellariifom coracoid that in all probability represents the larger species, Diomedeoides lipsiensis, and compare it to the coracoids of smaller diomedeoidids and extant procellariiforms. Using multivariate (Principal Component Analysis) and univariate analyses, we demonstrate that nearly all measurements are heavily size dependent, which makes the proportions and some other shape characters of little use as phylogenetic markers. Among eight measurements, the coracoid corpus width shows the highest correlation (higher than corpus depth) with body mass, permitting a precise calculation of over twofold difference in body mass between D. lipsiensis and smaller species. Among 16 qualitative characters analysed, the majority proved too variable to be used as markers of interfamily relationships and only 2–3, the ventral intermuscular line, sternocoracoid articulation (divided vs. undivided), and, with reservations, epimarginal crest vary consistently between the families. By far the most variable is the acrocoracoid process that tends to be deeper (more elongate dorsoventrally) in larger petrels but not in the albatrosses. However, the detailed shapes of the acrocoracoid heads are highly genus specific and suggest a genus‐level diversity among the Diomedeoididae from the Oligocene of Europe. The common features of the diomedeoidid coracoids are best interpreted as plesiomorphies, which accounts for some similarities to the Oceanitinae (that are probably basal among the crown‐group procellariiforms). The evidence from the coracoid is consistent with a stem‐group position of the Diomedeoididae as previously proposed by others. We emphasize the need of a group‐specific character analysis, primarily of allometries and levels of character variation, prior to a phylogenetic reconstruction.     

Inhibition of tomato (Solanum lycopersicum L.) root growth by cyanamide is due to altered cell division, phytohormone balance and expansin gene expression

Cyanamide (CA) has been reported as a natural compound produced by hairy vetch (Vicia villosa Roth.) and it was shown also to be an allelochemical, responsible for strong allelopathic potential in this species. CA phytotoxicity has been demonstrated on various plant species, but to date little is known about its mode of action at cellular level. Treatment of tomato (Solanum lycopersicum L.) roots with CA (1.2 mM) resulted in inhibition of growth accompanied by alterations in cell division, and imbalance of plant hormone (ethylene and auxin) homeostasis. Moreover, the phytotoxic effect of CA was also manifested by modifications in expansin gene expression, especially in expansins responsible for cell wall remodeling after the cytokinesis (LeEXPA9, LeEXPA18). Based on these results the phytotoxic activity of CA on growth of roots of tomato seedlings is likely due to alterations associated with cell division.     

Study of the differential transcription in liver of growth hormone receptor (GHR), insulin-like growth factors (IGF1, IGF2) and insulin-like growth factor receptor (IGF1R) genes at different postnatal developmental ages in pig breeds

The objective of this study was to determine hepatic expression levels of GHR, IGF1R, IGF1 and IGF2 genes in young growing gilts at different developmental ages (60–210 days) in five pig breeds: Polish Large White (PLW), Polish Landrace (PL), Pulawska (Pul), Duroc (Dur) and Pietrain (Pie). We studied the differences among pig breeds as well as within each breed for pigs in different developmental ages. Obtained results revealed major differences among breeds in hepatic gene expression of porcine GHR, IGF1R, IGF1 and IGF2 genes in different developmental ages. The differences among breeds of GHR expression were significantly higher in PLW, PL at the age of 60, 90, 120 days as compared to Pul, Dur and Pie. In turn, the highest level of IGF1R expression was observed in PL at age of 150, 180 and 210 days, whereas in case of IGF1 the highest level was recorded in Pie gilts at the age of 60 and 90 days. Moreover trait associated study revealed highly significant correlations between hepatic expressions of IGF1R and IGF2 genes and carcass composition traits (P < 0.01) The results of study suggest that porcine GHR, IGF1R, IGF1 and IGF2 genes may be potential candidate genes for postnatal growth and carcass composition traits. Therefore, the implementation of the hepatic expression of GH/IGF genes into the pig breeding and gene assisted selection program in different pig breeds should be considered. However, further population wide study is needed to clarify the hepatic expression association with economic traits, such as body growth, meat quality and carcass composition traits.     

Gallium(III), cobalt(III) and copper(II) protoporphyrin IX exhibit antimicrobial activity against Porphyromonas gingivalis by reducing planktonic and biofilm growth and invasion of host epithelial cells

Porphyromonas gingivalis acquires heme for growth, and initiation and progression of periodontal diseases. One of its heme acquisition systems consists of the HmuR and HmuY proteins. This study analyzed the antimicrobial activity of non-iron metalloporphyrins against P. gingivalis during planktonic growth, biofilm formation, epithelial cell adhesion and invasion, and employed hmuY, hmuR and hmuY-hmuR mutants to assess the involvement of HmuY and HmuR proteins in the acquisition of metalloporphyrins. Iron(III) mesoporphyrin IX (mesoheme) and iron(III) deuteroporphyrin IX (deuteroheme) supported planktonic growth of P. gingivalis cells, biofilm accumulation, as well as survival, adhesion and invasion of HeLa cells in a way analogous to protoheme. In contrast, cobalt(III), gallium(III) and copper(II) protoporphyrin IX exhibited antimicrobial activity against P. gingivalis, and thus represent potentially useful antibacterial compounds with which to target P. gingivalis. P. gingivalis hmuY, hmuR and hmuY-hmuR mutants showed decreased growth and infection of epithelial cells in the presence of all metalloporphyrins examined. In conclusion, the HmuY protein may not be directly involved in transport of free metalloporphyrins into the bacterial cell, but it may also play a protective role against metalloporphyrin toxicity by binding an excess of these compounds.     

Decrease in salivary lactoferrin output in chronically intoxicated alcohol-dependent patients

Salivary lactoferrin is a glycoprotein involved in the elimination of pathogens and the prevention of massive overgrowth of microorganisms that affect oral and general health. A high concentration of lactoferrin in saliva is often considered to be a marker of damage to the salivary glands, gingivitis, or leakage through inflamed or damaged oral mucosa, infiltrated particularly by neutrophils. We conducted a study to determine the effect of chronic alcohol intoxication on salivary lactoferrin concentration and output. The study included 30 volunteers consisting of ten non-smoking male patients after chronic alcohol intoxication (group A), and 20 control nonsmoking male social drinkers (group C) with no history of alcohol abuse. Resting whole saliva was collected 24 to 48 hours after a chronic alcohol intoxication period. Lactoferrin was assessed by enzyme-linked immunosorbent assay. For all participants, the DMFT index (decayed, missing, or filled teeth), gingival index (GI) and papilla bleeding index (PBI) were assessed. The differences between groups were evaluated using the Mann-Whitney U test. We noticed significantly decreased salivary flow (SF) in alcohol dependent patients after chronic alcohol intoxication (A), compared to the control group (C). Although there was no significant difference in salivary lactoferrin concentration between the alcohol dependent group A and the control group C, we found significantly decreased lactoferrin output in group A compared to group C. We found a significant correlation between the amount of daily alcohol use and a decrease in lactoferrin output. There was a significant increase in GI and a tendency of PBI to increase in group A compared to group C. We demonstrated that chronic alcohol intoxication decreases SF and lactoferrin output. The decreased lactoferrin output in persons chronically intoxicated by alcohol may be the result of lactoferrin exhaustion during drinking (due to its alcohol-related lower biosynthesis or higher catabolism) or to decreased function of neutrophils affected by the ethanol. The poorer periodontal state in alcohol dependent persons compared to controls may be a result of lower salivary flow and decreased protection of the oral cavity by lactoferrin.     

Dose distribution homogeneity in two TBI techniques—Analysis of 208 irradiated patients conducted in Stanislaw Leszczynski Memorial Hospital,Katowice

BackgroundTo analyze and compare dose distribution homogeneity in selected points (especially in the chest wall region) for patients irradiated with two different TBI techniques to achieve a uniform total dose (excluding lungs area) specified in the range of 11.4–14.0 Gy.Material and methodsFrom August 2000 to December 2009, a group of 158 patients was treated by the use of 15 MV photon irradiation consisting of six fractions: four opposed lateral and two anterior–posterior/posterior–anterior (AP/PA). Patients were irradiated with the fraction dose of 2 Gy twice a day for 3 consecutive days. The prescribed dose to PC point (specified at intersection of the beam axis with the mid-plane of the patient irradiated laterally) was 12 Gy. Since January 2010 until closing the study, another group of 50 patients was treated according to a modified protocol. The treatment was carried out in six lateral fractions only, twice a day, for three following days and a lateral lung shield was used for a part of total irradiation time. The measurements of doses in 20 selected points of patient's body were carried out by means of MOSFET detectors.ResultsThe modified TBI technique allows to achieve an expected homogenous dose in the points of interest similar to that obtained by using the initial protocol. The calculated and measured in vivo doses met the specified range of 11.4–14 Gy for both applied TBI protocols.ConclusionsOur results indicate that for all patients the homogenous dose distribution in the specified range was achieved.     

Preliminary in vitro study on the effect of xanthohumol on rumen methanogenesis

There is a great interest in reducing the methane emission from ruminants as one possible cause of global warming. The aim of the presented study was to determine the effects of xanthohumol, one of the hop (Humulus lupulus) phytofactors, on methane production, microbial population and basic parameters of ruminal fermentation. The experiment was carried out in a batch culture system. The basic substrate (400 mg) consisting of meadow hay and barley meal (60:40) was supplemented with 0 (Control), 0.1, 0.2 or 1.0 mg of xanthohumol. The basic parameters of rumen fermentation and composition of microbial population were measured after 24 h of incubation. For the first time, the results of this in vitro study have demonstrated that xanthohumol is capable to reduce the methane production, even at the lowest dose applied (0.1 mg/400 mg). The observed reduction in methane production by 12-13% was not accompanied by altering the basic rumen fermentation parameters. However, the practical utility of this supplement needs further investigation under long-term in vivo conditions.     

Adults of European ant‐like stone beetles (Coleoptera: Staphylinidae: Scydmaeninae) Scydmaenus tarsatus Müller & Kunze and Scydmaenus hellwigii (Herbst) prey on soft‐bodied arthropods

Scydmaenine beetles are commonly described as predators specialized in capturing and feeding on armored mites of the order Oribatida, and documented cases of feeding on other live arthropods have not been known. Based on laboratory observations and a broad choice of Acari (armored and soft‐bodied) and other soil arthropods, food preferences and associated behavior of two scydmaenine species are clarified and described. Adults of Scydmaenus tarsatus ignored oribatid and mesostigmatan mites, but readily attacked and fed on a soft‐bodied Rhizoglyphus sp. (Acaridae), and on small springtails, especially on Ceratophysella denticulata (Hypogastruridae). A water drinking behavior was observed for this species, not reported previously in any Staphylinidae. Scydmaenus hellwigii ignored all tested Acari (including Rhizoglyphus) and scavenged on dead neanurine collembolans or freshly cut pieces of large springtails; a long term culture was maintained by feeding beetles with isotomid springtails. Previously reported strict specialization of Scydmaenus as a predator on Oribatida was not confirmed and it is concluded that the studied species feed on live soft‐bodied organisms and scavenge on dead arthropods.