Reduced microvascular volume and hemispherically deficient vasoreactivity to hypercapnia in acute ischemia: MRI study using permanent middle cerebral artery occlusion rat model

Vasoreactivity to hypercapnia has been used for assessing cerebrovascular tone and control altered by ischemic stroke. Despite the high prognostic potential, traits of hypercapnia-induced hemodynamic changes have not been fully characterized in relation with baseline vascular states and brain tissue damage. To monitor cerebrovascular responses, T2- and T2*-weighted magnetic resonance imaging (MRI) images were acquired alternatively using spin- and gradient-echo echo plannar imaging (GESE EPI) sequence with 5% CO₂ gas inhalation in normal (n=5) and acute stroke rats (n=10). Dynamic relative changes in cerebrovascular volume (CBV), microvascular volume (MVV), and vascular size index (VSI) were assessed from regions of interest (ROIs) delineated by the percent decrease of apparent diffusion coefficient (ADC). The baseline CBV was not affected by middle cerebral artery occlusion (MCAO) whereas the baseline MVV in ischemic areas was significantly lower than that in the rest of the brain and correlated with ADC. Vasoreactivity to hypercapnic challenge was considerably attenuated in the entire ipsilesional hemisphere including normal ADC regions, in which unsolicited, spreading depression-associated increases of CBV and MVV were observed. The lesion-dependent inhomogeneity in baseline MVV indicates the effective perfusion reserve for accurately delineating the true ischemic damage while the cascade of neuronal depolarization is probably responsible for the hemispherically lateralized changes in overall neurovascular physiology.     

Maternal diets matter for children's dietary quality: Seasonal dietary diversity and animal‐source foods consumption in rural Timor‐Leste

Improving the dietary quality of women and children is essential to reduce all forms of malnutrition. In this study, we assessed seasonal child and maternal dietary diversity and consumption of animal‐source foods (ASF), using 1,236 observations from combined data collected among 167 mother–child dyads in rural Timor‐Leste. We used generalized linear and logistic mixed‐effects models to examine the dietary differentials of mothers and children in two agricultural livelihood zones and across the seasons, as well as to identify household and agroecological characteristics associated with children's dietary quality in relation to their mothers'. We found dietary quality to be marginally better in coastal than in mid‐altitude zones. However, women's diets were strikingly poor, and their intake of ASF was lower than among children. Mothers exhibited preferential allocation patterns of specific ASF, dairy products and eggs, to children. The intake of ASF was predicted by seasonality. Flesh foods and red meat were much more likely to be consumed during the dry season, when cultural ceremonies are often performed. We found a positive and strongly significant association between children's dietary indicators—dietary diversity score, minimum dietary diversity and ASF consumption, and those of their mothers'. Maternal dietary quality and educational attainment, more so than agroecological characteristics, were explanatory factors of children's diet. Our study highlights that addressing the dietary quality of children in Timor‐Leste would benefit from improving women's diets through better access to nutritious foods and to secondary education.     

全身振动训练联合正弦交变电磁场对去卵巢骨质疏松大鼠骨密度、骨代谢指标的影响研究

目的探讨全身振动训练联合正弦交变电磁场对去卵巢骨质疏松大鼠骨密度、骨代谢、骨生物力学性能的影响。方法将100只大鼠随机分为切除卵巢组和对照组,分别进行卵巢切除术和假手术,大鼠进行6周恢复,恢复后将造模成功的切除卵巢大鼠随机分为模型组(MO组)、全身振动训练组(W组)、正弦交变电磁场组(S组)、全身振动训练+正弦交变电磁场组(WS组),对照组列为假手术组(SO组),进行为期16周干预,干预结束后对大鼠进行骨密度、骨代谢、骨生物力学性质的检测。结果16周干预完成后,MO组、S组大鼠体质量显著高于SO组、W组、WS组大鼠(P0. 05); W组、WS组、SO组大鼠骨密度指标、血清雌二醇浓度指标明显高于大鼠MO组(P0. 05); SO组大鼠血清雌二醇浓度指标明显高于S组、W组、WS组(P0. 05); M组大鼠血清OC、ALP浓度明显高于SO组、W组、S组、WS组大鼠(P0. 05);尿液DPD/Cre、Ca/Cre、P/Cre浓度方面,M组大鼠明显高于SO组、W组、S组、WS组大鼠(P0. 05)。SO组、W组、S组、WS组大鼠股骨最大载荷和弹性模型明显高于MO组大鼠(P0. 05)。SO组、W组、S组、WS组大鼠股骨断裂载荷组间无明显差异(P0. 05); SO组、W组、S组、WS组大鼠股骨弹性模量明显高于MO组大鼠(P0. 05)。SO组大鼠股骨弹性模量明显高于S组大鼠(P0. 05),但与W组、WS组大鼠没有明显差异(P0. 05)。L4椎体压缩试验,SO组、W组、S组、WS组大鼠股骨最大载荷和弹性模型明显高于MO组大鼠(P0. 05)。SO组大鼠高于S组、W组,差异有统计学意义(P0. 05),但与WS组大鼠没有明显差异(P0. 05)。结论全身振动训练、正弦交变电磁场、全身振动训练联合正弦交变电磁场3种干预方式施用于去卵巢骨质疏松大鼠均能提升骨密度、抑制骨吸收、平衡骨代谢、改善骨骼结构力学和材料力学性能。而全身振动训练联合正弦交变电磁场能的治疗效果优于单纯使用全身振动训练或正弦交变电磁场,在临床应用中有一定推广价值。     

Drug discovery strategies for acute radiation syndrome

Introduction: There are at the minimum two major, quite different approaches to advance drug discovery. The first being the target-based drug discovery (TBDD) approach that is commonly referred to as the molecular approach. The second approach is the phenotype-based drug discovery (PBDD), also known as physiology-based drug discovery or empirical approach.

Area covered: The authors discuss, herein, the need for developing radiation countermeasure agents for various sub-syndromes of acute radiation syndromes (ARS) following TBDD and PBDD approaches. With time and continuous advances in radiation countermeasure drug development research, the expectation is to have multiple radiation countermeasure agents for each sub-syndrome made available to radiation exposed victims.

Expert opinion: The majority of the countermeasures currently being developed for ARS employ the PBDD approach, while the TBDD approach is clearly under-utilized. In the future, an improved drug development strategy might be a ‘hybrid’ strategy that is more reliant on TBDD for the initial drug discovery via large-scale screening of potential candidate agents, while utilizing PBDD for secondary screening of those candidates, followed by tertiary analytics phase in order to pinpoint efficacious candidates that target the specific sub-syndromes of ARS.     

Utility of food pellets containing 1-aminobenzotriazole for longer term in vivo inhibition of cytochrome P450 in mice

1. The utility of 1-aminobenzotriazole (ABT), incorporated in food, has been investigated as an approach for longer term inhibition of cytochrome P450 (P450) enzymes in mice.

2. In rats, ABT inhibits gastric emptying, to investigate this potential limitation in mice we examined the effect of ABT administration on the oral absorption of NVS-CRF38. Two hour prior oral treatment with 100?mg/kg ABT inhibited the oral absorption of NVS-CRF38, T_max was 4?hours for ABT-treated mice compared to 0.5?hours in the control group.

3. A marked inhibition of hepatic P450 activity was observed in mice fed with ABT containing food pellets for 1?month. P450 activity, as measured by the oral clearance of antipyrine, was inhibited on day 3 (88% of control), week 2 (83% of control) and week 4 (80% of control).

4. T_max values for antipyrine were comparable between ABT-treated mice and the control group, alleviating concerns about impaired gastric function.

5. Inclusion of ABT in food provides a minimally invasive and convenient approach to achieve longer term inhibition of P450 activity in mice. This model has the potential to enable pharmacological proof-of-concept studies for research compounds which are extensively metabolised by P450 enzymes.     

Rodent models of diet-induced type 2 diabetes mellitus: A literature review and selection guide

Several research teams have focused on finding the “ideal” animal model that reflects the pathophysiological changes and closely simulates the metabolic characteristics of patients with type 2 diabetes. However, the multitude of studies on this topic has resulted in large variations, making the models difficult to compare, as the measured parameters vary significantly. Additionally, selecting the appropriate animal model for a new study has become more difficult due to the increasing number of background variables. This article gives a detailed overview of the literature, covering the entire range of animal models and model characteristics, and most importantly, provides guidance for selecting the most suitable model for specific research goals in the future.     

白藜芦醇对酒精诱导雄性大鼠骨量减少和骨强度降低的保护作用

目的探索白藜芦醇对酒精诱导雄性大鼠骨量减少和骨强度降低的影响。方法 30只12周雄性大鼠随机分为对照组、模型组和治疗组3组,每组10只。模型组和治疗组大鼠给予0.4 mL/100 g的20%乙醇溶液,每周3次。治疗组接受白藜芦醇40 mg/kg治疗,每日一次,治疗为期12周。治疗结束时收集血清和股骨对治疗结果进行评价。结果治疗12周后,治疗组的股骨骨密度较模型组显著升高,差异有统计学意义(P0.05);Mircro-CT显示治疗组大鼠股骨干骺端较模型组具有更多骨小梁以及更佳的骨微观参数,差异有统计学意义(P0.05);生物力学结果显示治疗组股骨的极限载荷和峰值负荷较模型组显著升高,差异有统计学意义(P0.05);而血清检测结果表明治疗组的碱性磷酸酶和骨钙素较模型组明显降低,差异有统计学意义(P0.05)。结论白藜芦醇对酒精诱导雄性大鼠骨量减少和骨强度降低有一定的保护作用。     

Protection of White Leghorn chickens by recombinant fowlpox vector vaccine with an updated H5 insert against Mexican H5N2 avian influenza viruses

Despite decades of vaccination, surveillance, and biosecurity measures, H5N2 low pathogenicity avian influenza (LPAI) virus infections continue in Mexico and neighboring countries. One explanation for tenacity of H5N2 LPAI in Mexico is the antigenic divergence of circulating field viruses compared to licensed vaccines due to antigenic drift. Our phylogenetic analysis indicates that the H5N2 LPAI viruses circulating in Mexico and neighboring countries since 1994 have undergone antigenic drift away from vaccine seed strains. Here we evaluated the efficacy of a new recombinant fowlpox virus vector containing an updated H5 insert (rFPV-H5/2016), more relevant to the current strains circulating in Mexico. We tested the vaccine efficacy against a closely related subcluster 4 Mexican H5N2 LPAI (2010 H5/LP) virus and the historic H5N2 HPAI (1995 H5/HP) virus in White Leghorn chickens. The rFPV-H5/2016 vaccine provided hemagglutinin inhibition (HI) titers pre-challenge against viral antigens from both challenge viruses in almost 100% of the immunized birds, with no differences in number of birds seroconverting or HI titers among all tested doses (1.5, 2.0, and 3.1 log₁₀ mean tissue culture infectious doses/bird). The vaccine conferred 100% clinical protection and a significant decrease in oral and cloacal virus shedding from 1995 H5/HP virus challenged birds when compared to the sham controls at all tested doses. Virus shedding titers from vaccinated 2010 H5/LP virus challenged birds significantly decreased compared to sham birds especially at earlier time points. Our results confirm the efficacy of the new rFPV-H5/2016 against antigenic drift of LPAI virus in Mexico and suggest that this vaccine would be a good candidate, likely as a primer in a prime-boost vaccination program.     

动物瘢痕模型的相关研究进展

皮肤损伤后的异常愈合会导致病理性瘢痕的产生。病理性瘢痕的出现不仅影响美观,严重时还会造成心理和生理功能障碍。病理性瘢痕的机制研究对于瘢痕治疗有极为重要的意义。其中,动物瘢痕模型是目前研究病理性瘢痕的重要模型手段之一。理想的动物瘢痕模型应该在组织学、细胞学等层面尽可能接近于人类的病理性瘢痕。该文分别从传统技术动物瘢痕中的啮齿类动物模型、兔耳模型和猪模型,以及新技术动物瘢痕模型这两个方面,结合近年来在瘢痕领域应用较多的研究,进行了相应系统的阐述。     

脊柱化脓性感染动物模型的建立及应用进展

手术部位感染是脊柱手术后常见且非常严重的并发症,严重影响患者的身体健康。尽管手术操作无菌细致,及时给予适当的全身抗生素,但手术部位感染率仍然很高[1-2]。据报道,我国脊柱手术感染的风险从0.5%~7.8%不等[3-4]。糖尿病、肥胖、高血压等疾病显著增加脊柱术后感染,感染后治疗的费用可达10多万美元[5],大大增加了患者的经济负担。