Chemopreventive effects of hydroxymatairesinol on uterine carcinogenesis in Donryu rats

Hydroxymatairesinol (HMR), obtained from the heartwood of spruce (Picea abies), has been demonstrated to exert chemo-preventive effects on the development of mammary tumors in rats. To examine the influence of HMR on uterine carcinogenesis, adult Donryu rats were initiated with a single intrauterine treatment of N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) at 11 weeks of age and fed thereafter 0, 200, or 600 ppm HMR mixed in the soy-containing diet until 15 months of age. Incidences of uterine adenocarcinoma in both 200 and 600 ppm HMR-dosed groups were significantly reduced to 11% and 15%, respectively, less than 50% of 0 ppm, at the end of the experiment (P < 0.05). A delay in the start of persistent estrus by HMR was observed at 8 months of age compared with controls given carcinogen alone. From urinalysis, HMR was metabolized mainly to enterolactone and hydroxyenterolactone. These findings suggest that HMR or its metabolites exert chemo-preventive effects in the rat ENNG-uterine carcinogenesis model.     

Cardiac Repolarization and Autonomic Regulation during Short-Term Cold Exposure in Hypertensive Men: An Experimental Study

Objectives

The aim of our study was to assess the effect of short-term cold exposure, typical in subarctic climate, on cardiac electrical function among untreated middle-aged hypertensive men.

Methods

We conducted a population-based recruitment of 51 hypertensive men and a control group of 32 men without hypertension (age 55–65 years) who underwent whole-body cold exposure (15 min exposure to temperature −10°C, wind 3 m/s, winter clothes). Conduction times and amplitudes, vectorcardiography, arrhythmias, and heart rate variability (autonomic nervous function) were assessed.

Results

Short-term cold exposure increased T-peak to T-end interval from 67 to 72 ms (p<0.001) and 71 to 75 ms (p<0.001) and T-wave amplitude from 0.12 to 0.14 mV (p<0.001) and from 0.17 to 0.21 mV (p<0.001), while QTc interval was shortened from 408 to 398 ms (p<0.001) and from 410 to 401 ms (p<0.001) among hypertensive men and controls, respectively. Cold exposure increased both low (from 390 to 630 ms² (p<0.001) and 380 to 700 ms² (p<0.001), respectively) and high frequency heart rate variability (from 90 to 190 ms² (p<0.001) and 150 to 300 ms² (p<0.001), respectively), while low-to-high frequency-ratio was reduced. In addition, the frequency of ventricular ectopic beats increased slightly during cold exposure. The cold induced changes were similar between untreated hypertensive men and controls.

Conclusions

Short-term cold exposure with moderate facial and mild whole body cooling resulted in prolongation of T-peak to T-end interval and higher T-wave amplitude while QTc interval was shortened. These changes of ventricular repolarization may have resulted from altered cardiac autonomic regulation and were unaffected by untreated hypertension.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02007031","term_id":"NCT02007031"}}NCT02007031     

Reduced natriuretic response to acute sodium loading in COMT Gene deleted mice

Background  

The intrarenal natriuretic hormone dopamine (DA) is metabolised by catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO). Inhibition of COMT, as opposed to MAO, results in a potent natriuretic response in the rat. The present study in anaesthetized homozygous and heterozygous COMT gene deleted mice attempted to further elucidate the importance of COMT in renal DA and sodium handling. After acute intravenous isotonic sodium loading, renal function was followed.     

The role of land cover in bioclimatic models depends on spatial resolution

Aim We explored the importance of climate and land cover in bird species distribution models on multiple spatial scales. In particular, we tested whether the integration of land cover data improves the performance of pure bioclimatic models. Location Finland, northern Europe. Methods The data of the bird atlas survey carried out in 1986–89 using a 10 × 10 km uniform grid system in Finland were employed in the analyses. Land cover and climatic variables were compiled using the same grid system. The dependent and explanatory variables were resampled to 20‐km, 40‐km and 80‐km resolutions. Generalized additive models (GAM) were constructed for each of the 88 land bird species studied in order to estimate the probability of occurrence as a function of (1) climate and (2) climate and land cover variables. Model accuracy was measured by a cross‐validation approach using the area under the curve (AUC) of a receiver operating characteristic (ROC) plot. Results In general, the accuracies of the 88 bird–climate models were good at all studied resolutions. However, the inclusion of land cover increased the performance of 79 and 78 of the 88 bioclimatic models at 10‐km and 20‐km resolutions, respectively. There was no significant improvement at the 40‐km resolution. In contrast to the finer resolutions, the inclusion of land cover variables decreased the modelling accuracy at 80km resolution. Main conclusions Our results suggest that the determinants of bird species distributions are hierarchically structured: climatic variables are large‐scale determinants, followed by land cover at finer resolutions. The majority of the land bird species in Finland are rather clearly correlated with climate, and bioclimate envelope models can provide useful tools for identifying the relationships between these species and the environment at resolutions ranging from 10 km to 80 km. However, the notable contribution of land cover to the accuracy of bioclimatic models at 10–20‐km resolutions indicates that the integration of climate and land cover information can improve our understanding and model predictions of biogeographical patterns under global change.     

Identifying resuspended particles using isotope ratios

Three simple methods were developed to estimate the proportion of particles in lake water derived from resuspended material. These techniques use the different distributions of long and short-lived radioisotopes sorbed onto particles and were tested in the three basins of Lake Erie using ⁷Be, ¹³⁷Cs and ²¹⁰Po/²¹⁰Pb.While the concentration of ²¹⁰Po on particles did not vary significantly in the lake, resuspended particles were characterized by high concentrations of ¹³⁷Cs and low concentrations of ⁷Be. The distribution of these radioisotopes is consistent with a simple mixing model in which the fraction of particles in the lake water derived from resuspension ranged from 8% to about 100%. Higher concentrations of resuspended particles were found in deeper samples from the nepheloid layer and in the shallow western basin where thermal stratification was very weak.     

Are biological classifications of headwater streams concordant across multiple taxonomic groups?

1. Studies assessing human impacts on freshwater ecosystems are typically based on a single taxonomic group, often macroinvertebrates or fish. Unfortunately, the degree to which such macroinvertebrate or fish‐based surveys can be generalised across other taxonomic groups remains largely unknown. A prerequisite for useful generalisations is that different taxonomic groups exhibit concordant patterns of community structure across sites. 2. We examined the concordance among fish, benthic macroinvertebrates and bryophytes in 32 streams in a boreal catchment in Finland. Our goal was to test how consistently different taxonomic groups classify stream sites; for example, can site groupings based on macroinvertebrates be used as a surrogate for bryophyte or fish assemblage classification? 3. Our results show that community classifications in headwater streams are not concordant across taxonomic groups, at least not at the within‐river system scale. The lack of concordance reflected the fact that all three groups responded to different environmental factors. Macroinvertebrate community structure was mainly correlated with stream size and pH, whereas bryophytes were related to water colour, nutrient content and in‐stream habitat variability. Fish community structure was best described by stream depth, substrate size and water oxygen concentration. 4. Our results suggest that great care should be taken when typologies based on benthic macroinvertebrates, or any other taxonomic group, are extrapolated to other groups in creating typologies of lotic environments.     

Direct analysis of nitrocatechol-type glucuronides in urine by capillary electrophoresis–electrospray ionisation mass spectrometry and tandem mass spectrometry

Direct, quantitative capillary electrophoresis–electrospray ionisation mass spectrometric (CE–ESI-MS) and tandem mass spectrometric (CE–ESI-MS–MS) methods are described for the quantitation of 3-O-glucuronides of E- and Z-entacapone isomers (EEG and EZG) and tolcapone (TG) in urine. 3-O-Glucuronide of nitecapone was used as internal standard. Good separation of glucuronides was achieved with 20 mM ammonium acetate as separation solution at pH 6.84. Stacking was used to increase the sensitivity of the method by introducing samples in 5 mM ammonium acetate. CE–ESI-MS and CE–ESI-MS–MS methods are linear with correlation coefficients better than 0.9983 and 0.9982, and repeatable with relative standard deviations below 9 and 14%, respectively. The limit of detection (LOD) in CE–ESI-MS at signal-to-noise ratio 3 is 100 ng/ml for EEG and EZG and 250 ng/ml for TG. The CE–ESI-MS–MS method was the more sensitive; LOD was 7 ng/ml for all compounds, without any concentration of the sample.     

Enzyme-assisted synthesis and characterization of glucuronide conjugates of neuroactive steroids

Synthesis of reference standards is needed to determine the presence and function of steroid glucuronides in the brain or other tissues, because commercial sources of steroid glucuronide standards are limited or unavailable. In the present study porcine, rat, and bovine liver microsomes were tested to evaluate their ability to glucuronidate eight neurosteroids and neuroactive steroids of various types: dehydroepiandrosterone, pregnenolone, isopregnanolone, 5alpha-tetrahydrodeoxycorticosterone, corticosterone, cortisol, beta-estradiol, and testosterone. In general, the glucuronidation efficiency of rat liver was rather poor compared with that of bovine and porcine liver microsomes. Since porcine liver apparently has a relatively large amount of dehydrogenase, its microsomes also produced dehydrogenated steroids and their glucuronides, as well as various regioisomers in which the site of glucuronidation varied. In contrast, bovine liver microsomes produced mainly a single major glucuronidation product and few dehydrogenation products and gave the best overall yield for two-third of the steroids tested. The enzymatic synthesis of five glucuronides of four steroids was carried out and the conditions, purification, and analytical methods for the glucuronidation products were optimized. The steroid glucuronides synthesized were characterized by nuclear magnetic resonance spectroscopy (NMR) and liquid chromatography-mass spectrometry (LC-MS). The stereochemically pure steroid glucuronide conjugates were recovered in milligram amounts (yield 10-78%) and good purity (>85-90%), which is sufficient for LC-MS/MS method development and analyses of steroid glucuronides in biological matrices such as brain, urine, or plasma.