Intestinal absorption of forsythoside A in different compositions of Shuang-Huang-Lian

Shuang-Huang-Lian (SHL), a traditional Chinese formula containing Lonicerae japonicae flos (LJF), Scutellariae radix (SR) and Forsythiae fructus (FF), is commonly used to treat acute upper respiratory tract infection, acute bronchitis and light pneumonia. Forsythoside A is one of the main active ingredients in Forsythiae fructus, a key herb in SHL. In the present study, effects of different compositions in SHL on the intestinal absorption of forsythoside A were investigated. The observations from in situ intestinal circulation model showed that A/%(h^− 1) of forsythoside A in FF + LSF, FF + SR and SHL were all reduced greatly compared with that in FF. However, in pharmacokinetics study, C_max and AUC_0 → 1440 of forsythoside A all increased and T_1/2 prolonged in SHL, FF + LJF and FF + SR compared with FF. The results indicated that the different compositions of SHL decreased absorption but increased bioavailability of forsythoside A, which may be related to its metabolism inhibited in intestine or liver.     

The relative plasma availabilities of ivermectin in reindeer (Rangifer tarandus tarandus) following subcutaneous and two different oral formulation applications

Background

Overwintering (breeding) reindeer (Rangifer tarandus tarandus) are commonly treated with ivermectin against parasitic infestations once yearly in autumn-winter roundups. The only preparations registered to reindeer are those for subcutaneous injection. However, also oral extra-label ivermectin administration is used. Twenty-six, 8-month-old reindeer calves were randomly allocated into three groups. Group 1 (n = 9) received oral ivermectin mixture (Ivomec® vet mixt. 0.8 mg/ml, oral ovine liquid drench formulation), Group 2 (n = 9) oral ivermectin paste (Ivomec® vet 18.7 mg/g equine paste), and Group 3 (n = 8) subcutaneous injection of ivermectin (Ivomec® 10 mg/ml vet inj.), each group at a dose of 200 μg/kg body weight. Blood samples were collected at treatment and at days 1, 2, 3, 6, 9 and 16 post treatment. Plasma concentrations of ivermectin were determined by high-pressure liquid chromatography (HPLC) with fluorescence detection.

Results

The peak plasma concentration (C_max) was reached by 2 days after each treatment. The C_max and Area Under Curve (AUC) differed significantly between the groups: C_max was 30.2 ± 3.9, 14.9 ± 5.7 and 63.1 ± 13.1 ng/ml, and AUC_∞ was 2881 ± 462, 1299 ± 342 and 6718 ± 1620 ng*h/ml for groups 1, 2 and 3, respectively (mean ± standard deviation).

Conclusions

The differences in plasma concentrations of ivermectin are concomitant with earlier observed differences in antiparasitic efficacy, which discounts the use of the equine paste in reindeer in favour of the oral ovine liquid drench formulation, or preferably, the reindeer-registered subcutaneous injection formulation.     

Pharmacokinetics and dynamics of mycophenolate mofetil after single‐dose oral administration in juvenile dachshunds

Mycophenolate mofetil (MMF) is recommended as an alternative/complementary immunosuppressant. Pharmacokinetic and dynamic effects of MMF are unknown in young‐aged dogs. We investigated the pharmacokinetics and pharmacodynamics of single oral dose MMF metabolite, mycophenolic acid (MPA), in healthy juvenile dogs purpose‐bred for the tripeptidyl peptidase 1 gene (TPP1) mutation. The dogs were heterozygous for the mutation (nonaffected carriers). Six dogs received 13 mg/kg oral MMF and two placebo. Pharmacokinetic parameters derived from plasma MPA were evaluated. Whole‐blood mitogen‐stimulated T‐cell proliferation was determined using a flow cytometric assay. Plasma MPA C_max (mean ± SD, 9.33 ± 7.04 μg/ml) occurred at <1 hr. The AUC_0–∞ (mean ± SD, 12.84±6.62 hr*μg/ml), MRT_inf (mean ± SD, 11.09 ± 9.63 min), T1/2 (harmonic mean ± PseudoSD 5.50 ± 3.80 min), and k/d (mean ± SD, 0.002 ± 0.001 1/min). Significant differences could not be detected between % inhibition of proliferating CD5+ T lymphocytes at any time point (p = .380). No relationship was observed between MPA concentration and % inhibition of proliferating CD5+ T lymphocytes (R = .148, p = .324). Pharmacodynamics do not support the use of MMF in juvenile dogs at the administered dose based on existing therapeutic targets.     

Effects of tryptophan supplementation on plasma tryptophan and related hormone levels in heifers and dairy cows

This study was conducted to investigate the effects of rumen-protected tryptophan (125 g tryptophan per day) in heifers and dairy cows. Blood samples from dairy cows and heifers were collected for 24h in 3-h intervals on the day before tryptophan supplementation, on day 2, 5 and 7 of tryptophan supplementation, and in heifers additionally on d 14 after tryptophan supplementation was ceased. Plasma tryptophan, melatonin, serotonin, and prolactin concentrations were determined. Tryptophan plasma concentrations on d 5 were augmented at day (11:00 h) and nighttime (02:00 h), (P<0.05) in response to tryptophan supplementation in heifers by 119% and in dairy cows by 47%, respectively, as compared with d 0. Melatonin increased (P<0.05) in response to tryptophan supplementation in heifers, but not in cows. The effect of tryptophan supplementation on plasma tryptophan and melatonin was reversible as demonstrated in heifers on d 14 after cessation of tryptophan supplementation. Serotonin and prolactin in plasma did not respond to tryptophan supplementation. However, milk yield during morning milking increased significantly in tryptophan supplemented cows on d 1, 3 and 4 as compared to the day before tryptophan supplementation. Additional blood samples were taken during afternoon milking in cows at 1-min intervals for the analyses of oxytocin and prolactin on the day before the start and on d 7 of tryptophan supplementation. Milk flow curves were recorded during milking. No effect of tryptophan supplementation on the milking related release of oxytocin and prolactin and on any characteristic of milk flow was observed. In conclusion, tryptophan supplementation caused increased plasma tryptophan in cows and heifers and plasma melatonin in heifers. However, plasma serotonin, prolactin and oxytocin release in cows remained unchanged by tryptophan supplementation. Milk yield at morning milking increased slightly and transiently in response to tryptophan supplementation.     

Is bird incidence in Atlantic forest fragments influenced by landscape patterns at multiple scales?

The degree to which habitat fragmentation affects bird incidence is species specific and may depend on varying spatial scales. Selecting the correct scale of measurement is essential to appropriately assess the effects of habitat fragmentation on bird occurrence. Our objective was to determine which spatial scale of landscape measurement best describes the incidence of three bird species (Pyriglena leucoptera, Xiphorhynchus fuscus and Chiroxiphia caudata) in the fragmented Brazilian Atlantic forest and test if multi-scalar models perform better than single-scalar ones. Bird incidence was assessed in 80 forest fragments. The surrounding landscape structure was described with four indices measured at four spatial scales (400-, 600-, 800- and 1,000-m buffers around the sample points). The explanatory power of each scale in predicting bird incidence was assessed using logistic regression, bootstrapped with 1,000 repetitions. The best results varied between species (1,000-m radius for P. leucoptera; 800-m for X. fuscus and 600-m for C. caudata), probably due to their distinct feeding habits and foraging strategies. Multi-scale models always resulted in better predictions than single-scale models, suggesting that different aspects of the landscape structure are related to different ecological processes influencing bird incidence. In particular, our results suggest that local extinction and (re)colonisation processes might simultaneously act at different scales. Thus, single-scale models may not be good enough to properly describe complex pattern–process relationships. Selecting variables at multiple ecologically relevant scales is a reasonable procedure to optimise the accuracy of species incidence models.     

样本量对MaxEnt模型预测物种分布精度和稳定性的影响

以实际调查的4个物种的34个不同样本量(5,6,8,10,15,20,25,30,40,50,60,70,80,90,100,120,150,180,200,220,250,300,350,400,450,500,550,600,650,700,800,900,1 000,1 200)为例,模拟计算分析不同的样本量对MaxEnt物种分布模型的精度和稳定性的影响.结果表明:总体上来看,样本量的大小对MaxEnt模型预测物种空间分布的精度影响不大,在样本量较小时,精度不稳定,随着样本量的增大(训练数据在样本量50左右,检验数据在样本量120左右),MaxEnt模型的预测精度越来越稳定.     

In vitro metabolism in Sprague-Dawley rat liver microsomes of forsythoside A in different compositions of Shuang-Huang-Lian

Shuang–Huang–Lian (SHL), a traditional Chinese formula containing Lonicerae japonicae flos (LJF), Scutellariae radix (SR) and Forsythiae fructus (FF), is commonly used to treat acute upper respiratory tract infection, acute bronchitis and light pneumonia. Forsythoside A is one of the main active ingredients in Forsythiae fructus, a key herb in SHL. In the present study, effects of different compositions in SHL on the in vitro metabolism in Sprague–Dawley rat liver microsomes of forsythoside A were investigated. The observations from Sprague–Dawley rat liver microsomes in the presence of β-NADPH or UDPGA that forsythoside A may be the substrates of CYP3A4, CYP2C9, CYP1A2, UGT1A6, UGT1A3, UGT1A1 and UGT1A9; Chlorogenic acid may be the substrates of CYP3A4, CYP2C9, CYP1A2, CYP2C19, UGT1A6, UGT1A3 and UGT1A1; Baicalin may be the substrates of CYP3A4, CYP2C19, CYP1A2, UGT1A9, UGT1A1 and UGT1A3; Baicalein may be the substrates of CYP3A4, CYP2E1 and UGT1A6. It was also found that the residue of forsythoside A in SHL, FF + LJF and FF + SR was greatly increased compared with that in FF in Sprague–Dawley rat liver microsomes in the presence of β-NADPH or UDPGA, which indicated that the metabolism of forsythoside A in SHL may be influenced by chlorogenic acid in LJF acting on the CYP3A4, CYP2C9, CYP1A2, UGT1A6, UGT1A3 and UGT1A1; baicalin in SR acting on the CYP3A4, CYP1A2, UGT1A9, UGT1A1 and UGT1A3; baicalein acting on the CYP3A4 and UGT1A6 respectively.     

Applying species distribution modelling for the conservation of the threatened saproxylic Stag Beetle (Lucanus cervus)

Despite its size and attractiveness, many Lucanus cervus sites remain undetected in NW Europe because of its short flight period and its nocturnal activity. Therefore, present-day designated conservation areas for L. cervus are probably insufficient for a sustainable conservation of the species. We applied eight species distribution modelling techniques (artificial neural networks, classification tree analysis, generalised additive models, generalised boosting models, generalised linear models, mixture discriminant analysis, multiple adaptive regression splines and random forests) to predict the distribution of L cervus in Belgium using 10 randomly generated calibration and evaluation sets. We used AUC, sensitivity (% correctly predicted presences in the evaluation set) and specificity (% correctly predicted absences in the evaluation set) and Kappa statistics to compare model performances. To avoid the incorporation of only marginally suitable woodland sites into the Natura 2000 network, we, conservatively, considered the species as being present only in grid cells where all 10 randomly generated model sets predicted the species as such. Model performance was, on average, good allowing to predict the potential distribution of L. cervus accurately. According to the predicted distribution using the more robust prevalence threshold, only 5731 ha (11% of the potentially suitable area) is protected under the Natura 2000 scheme in Belgium. Subsequently, we categorised the potentially suitable woodlands into three conservation priority categories based on their surface area and the already designated Natura 2000 area. Including the most suitable L. cervus woodlands previously not included in the Natura 2000 sites within such network would require protecting an area of 15,260 ha. Finally, we discuss the implications of using species distribution modelling for nature policy decisions in designating conservation networks.     

Interplay between physical and predator landscapes affects transferability of shorebird distribution models

Coastal landscapes with extensive intertidal mudflats provide non-breeding habitat for Arctic shorebirds. Few attempts have been made to develop and test landscape-level models predicting the intertidal distribution of these birds. We modelled the distribution of a Holarctic species, Dunlin (Calidris alpina), at a hemispherically important non-breeding site, the Fraser River Delta, British Columbia, Canada, in seasons with different predator landscapes. We trained the models during a season when nocturnal predators were common and tested temporal transferability of the models on independent datasets when nocturnal predators were absent. Snowy Owls (Nyctea scandiaca) influenced Dunlin distribution and thus model transferability. After accounting for their presence, models displayed good to excellent discrimination, i.e. prediction of the instantaneous and cumulative (over low tide period) probability of mudflat use by Dunlin, in fore- and backcasting applications. Model calibration was good or else, where over-prediction was observed, the reason for the bias was identified. The distribution models may predict mudflat use by Dunlin and possibly related species given relevant data describing the intertidal landscape. The models are amenable to GIS application, describe the amount of use per hectare of the intertidal zone and can be used to determine and visualise relative and absolute suitability of intertidal areas. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.