Aim
Neuropeptide Y (NPY) co‐localized with noradrenaline in central and sympathetic nervous systems seems to play a role in the control of energy metabolism. In this study, the aim was to elucidate ...the effects and pathophysiological mechanisms of increased NPY in catecholaminergic neurones on accumulation of body adiposity.
Methods
Transgenic mice overexpressing NPY under the dopamine‐beta‐hydroxylase promoter (OE‐NPYDβH) and wild‐type control mice were followed for body weight gain and body fat content. Food intake, energy expenditure, physical activity, body temperature, serum lipid content and markers of glucose homoeostasis were monitored. Thermogenic and lipolytic responses in adipose tissues, and urine catecholamine and tissue catecholamine synthesizing enzyme levels were analysed as indices of sympathetic tone.
Results
Homozygous OE‐NPYDβH mice showed significant obesity accompanied with impaired glucose tolerance and insulin resistance. Increased adiposity was explained by neither increased food intake or fat absorption nor by decreased total energy expenditure or physical activity. Adipocyte hypertrophy and decreased circulating lipid levels suggested decreased lipolysis and increased lipid uptake. Brown adipose tissue thermogenic capacity was decreased and brown adipocytes filled with lipids. Enhanced response to adrenergic stimuli, downregulation of catecholamine synthesizing enzyme expressions in the brainstem and lower adrenaline excretion supported the notion of low basal catecholaminergic activity.
Conclusion
Increased NPY in catecholaminergic neurones induces obesity that seems to be a result of preferential fat storage. These results support the role of NPY as a direct effector in peripheral tissues and an inhibitor of sympathetic activity in the pathogenesis of obesity.
Clodronate is used in the treatment of osteoporosis, and malignancy-associated bone disease. The steady state pharmacokinetics and the dose equivalents of oral clodronate were assessed in subjects ...with various degrees of renal failure.
1,600 mg of clodronate was given orally mornings for 11 days to 14 healthy volunteers (creatinine clearance, CLCr, > 80 ml/min), and 18, 12 and 16 subjects with mild (50 - 80 ml/min), moderate (30 - 50 ml/min) and severe (< 30 ml/min) renal failure, respectively. Trough drug levels at 4, 7 and 11 days, and concentration-time curves for 72 h after the last dose were followed.
In all study groups, the trough drug levels achieved the kinetic steady state within 11 days. The area under the 24-h concentration-time curve (AUC0-24) enlarged and the elimination half-life (t1/2elim) prolonged progressively when the renal function was impaired. The maximum drug level and the time to maximum were not changed significantly in the renal failure. In the steady state phase, the diurnal drug excretion (E0-24) was not changed by the kidney function, but the renal drug clearance (CLD) decreased in close correlation with CLCr. The normal-to-failed AUC0-24 ratios in mild, moderate, and severe renal failure were 0.53, 0.43 and 0.31, respectively, when the ideally-matched counterpart was assumed as the normal reference to each renal failure group.
In mild, moderate and severe renal failure, 53%, 43% and 31% oral clodronate doses, respectively, resulted in drug AUCs similar to those in controls with normal (> 80 ml/min) CLCR.
► Sludge N and P are readily available for feedstock crops. ► Mycorrhiza improved nutrient availability of sludge. ► Sludge increased biomass accumulation in comparison to synthetic fertilizer. ► ...Sludge increased number of mycorrhizal spores in soil and root colonization. ► Sludge with mycorrhizal improve sustainability of bioenergy feedstocks.
Recycling nutrients saves energy and improves agricultural sustainability. Sewage sludge contains 2.6% P and 3.1% N, so the availability of these nutrients was investigated using four crops grown in either soil or sand. Further attention was paid to the role of mycorrhiza in improvement of nutrient availability. The content of heavy metals and metalloids in the feedstock was analyzed. Sewage sludge application resulted in greater biomass accumulation in ryegrass than comparable single applications of either synthetic fertilizer or digested sludge. Sewage sludge application resulted in more numerous mycorrhizal spores in soil and increased root colonization in comparison to synthetic fertilizer. All plants studied had mycorrhizal colonized roots, with the highest colonization rate in maize, followed by hemp. Sewage sludge application resulted in the highest P uptake in all soil-grown plants. In conclusion, sewage sludge application increased feedstock yield, provided beneficial use for organic wastes, and contributed to the sustainability of bioenergy feedstock production systems. It also improves the soil conditions and plant nutrition through colonization by mycorrhizal fungi as well as reducing leaching and need of synthetic fertilizers.
In this paper, the preliminary breakdown (PB) pulse train preceding the negative first return stroke (RS) is recorded using a broad band antenna system. These analyses were carried out in Johor ...Bahru, Malaysia and Florida, United States. This is a novel initiative at examining and identifying the characteristics of the PB pulse trains in the negative cloud-to-ground flashes observed in Malaysia. The arithmetic mean of the total pulse train duration is 12.3ms and the weighted arithmetic mean of the pulse durations and interpulse intervals are 11μs and 152μs, respectively. The arithmetic mean ratio between the maximum peak amplitude of the PB pulse and the peak RS electric field was 27.8%, and the corresponding value in Florida was 29.4%. The arithmetic mean of the time duration between the most active part of the pulse train, and the RS was 57.6ms in Malaysia and 22ms in Florida. A qualitative comparison of our results with those obtained earlier in Sri Lanka, Sweden and Finland supports the hypothesis that the PBP/RS ratio is higher in the northern regions compared to the tropical regions.
Low risk of breast cancer (BC) has been proposed to be associated with high intake of lignans. Some plant lignans are converted to mammalian lignans, e.g., enterolactone (ENL), suggested to be the ...biologically active lignan forms. Until now, little attention has been paid to the possible biological activities of plant lignans, even though some plant lignans are absorbed and present in serum and urine. In this study, we have investigated the antitumorigenic and endocrine-modulatory activities of different plant lignans in order to clarify the structure–activity relationships. 7-Hydroxymatairesinol (HMR) is converted to ENL, and both HMR and ENL inhibit the growth of 7,12-dimethylbenz
a-anthracene (DMBA)-induced mammary cancer. Nortrachelogenin (NTG) resembles HMR, but has a hydroxyl group at C-8 instead of C-7 and is not converted to ENL. In DMBA-model, NTG showed no inhibition of tumor growth, but increased the uterine weight. Furthermore, life-long exposure to NTG increased uterine weight in immature females and ventral prostate weight in adult males. In contrast, life-long exposure to HMR had no effects on uterine or prostate weights at any age. Our results indicate that a difference in the position of one hydroxyl group results in distinct biological responses in vivo
, as well as different lignan metabolite profiles.
The aim of this study was to evaluate the estrogenicity of genistein in the neonatal and adult male mouse reproductive tract. In intact adults, genistein (2.5 mg s.c./kg of body weight/day for 9 ...days) reduced testicular and serum testosterone concentrations, pituitary LH-content and prostate weight. In castrated adults, genistein (0.025–2.5 mg s.c./kg of body weight) increased expression of
c-fos gene in prostatic urethra. In adult, neonatally estrogenized mice showing an increased estrogen sensitivity, a 10-day treatment with genistein (2.5 mg s.c./kg of body weight) induced development of squamous epithelial metaplasia in prostatic collecting ducts. Neonatally, only a very high dose of genistein (1 mg/pup per day; i.e. ≈500 mg/kg of body weight) induced persistent structural changes, similar to those seen in mice treated neonatally with diethylstilbestrol, in the urethroprostatic complex. These results suggest that in adult males, genistein induces the typical estrogenic effects in doses comparable to those present in soy-based diets, while in neonatal animals, considerably higher doses are required to show estrogen-like activity.
Mixed cropping, including intercropping, is the oldest form of systemized agricultural production and involves the growing of two or more species or cultivars of the same species simultaneously in ...the same field. However, mixed cropping has been little by little replaced by sole crop systems, especially in developed countries. Some of the advantages of mixed cropping are, for example, resource use efficiency and yield stability, but there are also several challenges, such as weed management and competition. The boreal-nemoral region lies within the region 55 to 70°N. In this area, for example in Finland, the length of the thermal growing season varies from >105 to over 185 days. Typically, variation between locations and years is marked. However, during the year, there can be a wide range of temperature extremes between −70 and +30°C. The majority of cropping systems in this region are usually monocultures, except for forage grass mixtures. The possibility of having several crops in a mixture is very challenging in the region due to the short growing season and extreme cold temperatures, meaning that crop earliness and overwintering capacity are a considerable restriction for year-round mixed cropping. A further restriction is the quality requirements set by the industry. Our review will explore a range of mixed cropping possibilities for the boreal-nemoral region, including different possible combinations of spring, winter, perennial, biennial, catch, and cover crops. The reviewed mixed cropping systems could considerably improve the sustainability and efficiency of crop production.
We present a statistical technique for ranging the edges of active storms cell using a very simple narrowband receiver tuned to 1
MHz (the MW band in radio, just below HF frequencies). We show that a ...principle based on the “30–30 rule” can be used to define practical warning levels. From the measurements carried out in Finland, we show that the narrowband source intensities of cloud-to-ground lightning vary log-normally; this results in a ranging uncertainty of about 20%, which can be reduced if a suitable floating average is used. Based on one storm, we suggest that the differences between intra-cloud and ground-to-cloud signals at 1
MHz are small enough to make an IC–CG discrimination. Eliminating such a discrimination allows all lightning impulses to be used in the range and improves the accuracy, since more flashes are then available as inputs into the distance-estimation algorithm. Although the system is only validated against a single storm, we provide definitions by which this and other narrowband detectors could be independently verified; existing narrowband devices have not been verified in this manner, due in part to a lack of such standardized definitions.
Purpose
The study aimed to assess whether the more limiting factor in reproducibility of shear wave elastography (SWE) would be the operator dependency or the incompatibility of different ultrasound ...(US) devices. The interrater agreement with less experienced operators was studied.
Methods
A total of 24 healthy volunteers participated in the study (18 females, 6 males; range of age 27–55 years). SWE of biceps brachii (BB) and tibialis anterior (TA) muscles was performed on both sides from all participants in both longitudinal and transverse orientation of the transducer in respect to muscle fibers. Two operators repeated the SWE with two different US devices from different manufacturers (scanners 1 and 2).
Results
Intraclass correlation coefficient between the two operators was 0.91 (CI 0.88–0.93) for scanner 1 and 0.81 (CI 0.74–0.86) for scanner 2, respectively. Instead, there were significant differences in the SWE measurements between the two scanners, emphasizing in transverse orientation of the transducer. In the transverse transducer orientation, the mean shear wave velocity (SWV) in TA was 1.45 m/s (standard deviation SD ± 0.35 m/s) with scanner 1 and 2.35 m/s (SD ± 0.83 m/s) with scanner 2 (p < 0.001). In BB, the mean transverse SWV was 1.49 m/s (SD ± 0.35 m/s) with scanner 1 and 2.29 m/s (SD ± 0.63 m/s) with scanner 2 (p < 0.001). In longitudinal transducer orientation, the mean SWV in TA was 3.00 m/s (SD ± 0.73 m/s) with scanner 1 and 3.26 m/s (SD ± 0.42 m/s) with scanner 2 (p = 0.050). In BB, the mean longitudinal SWV was 3.60 m/s (SD ± 0.77 m/s) with scanner 1 and 3.96 m/s (SD ± 0.62 m/s) with scanner 2 (p = 0.019). The presented mean values were obtained by operator 1, there were no significant differences in the SWE measurements performed by the two operators.
Conclusion
The results implicate that the reproducibility of the SWE measurements depends rather on the used US device than on the operator. It is recommendable that clinics collect reference values with their own US device and consider threshold values presented in previous studies only directional.
Summary
In the present study, we have analysed the ability of Streptococcus pyogenes Group A streptococcus (GAS) to activate the NACHT‐domain‐, leucine‐rich repeat‐ and PYD‐containing protein 3 ...(NALP3) inflammasome complex in human monocyte‐derived macrophages and the molecules and signalling pathways involved in GAS‐induced inflammatory responses. We focused upon analysing the impact of dynamin‐dependent endocytosis and the role of major streptococcal virulence factors streptolysin O (SLO) and streptolysin S (SLS) in the immune responses induced by GAS. These virulence factors are involved in immune evasion by forming pores in host cell membranes, and aid the bacteria to escape from the endosome–lysosome pathway. We analysed cytokine gene expression in human primary macrophages after stimulation with live or inactivated wild‐type GAS as well as with live SLO and SLS defective bacteria. Interleukin (IL)‐1β, IL‐10, tumour necrosis factor (TNF)‐α and chemokine (C‐X‐C motif) ligand (CXCL)‐10 cytokines were produced after bacterial stimulation in a dose‐dependent manner and no differences in cytokine levels were seen between live, inactivated or mutant bacteria. These data suggest that streptolysins or other secreted bacterial products are not required for the inflammatory responses induced by GAS. Our data indicate that inhibition of dynamin‐dependent endocytosis in macrophages attenuates the induction of IL‐1β, TNF‐α, interferon (IFN)‐β and CXCL‐10 mRNAs. We also observed that pro‐IL‐1β protein was expressed and efficiently cleaved into mature‐IL‐1β via inflammasome activation after bacterial stimulation. Furthermore, we demonstrate that multiple signalling pathways are involved in GAS‐stimulated inflammatory responses in human macrophages.
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