Anti-hyperalgesic effects of two sphingosine derivatives in different acute and chronic models of hyperalgesia in mice

Background

The study evaluated the effects of two sphingosine derivatives N-(2-tert-butoxycarbamylhexadecyl)glutaramide (AA) and N-(1-benzyloxyhexadec-2-yl)glutaramide (OA) in different models of hypersensitivity in mice.

Relationship between Optimum Mini‐doses of Glucagon and Insulin Levels when Treating Mild Hypoglycaemia in Patients with Type 1 Diabetes – A Simulation Study

Hypoglycaemia remains the main limiting factor in type 1 diabetes management. We developed an insulin‐dependent glucagon dosing regimen for treatment of mild hypoglycaemia based on simulations. A validated glucose–insulin–glucagon model was used to describe seven virtual patients with insulin pump‐treated type 1 diabetes. In each simulation, one of ten different and individualized subcutaneous insulin boluses was administered to decrease plasma glucose (PG) from 7.0 to ≤3.9 mmol/l. Insulin levels were estimated as ratio of actual to baseline serum insulin concentration (se/ba‐insulin), insulin on board (IOB) or percentage of IOB to total daily insulin dose (IOB/TDD). Insulin bolus sizes were chosen to provide pre‐defined insulin levels when PG reached 3.9 mmol/l, where one of 17 subcutaneous glucagon boluses was administered. Optimum glucagon bolus to treat mild hypoglycaemia at varying insulin levels was the lowest dose that in most patients caused PG peak between 5.0 and 10.0 mmol/l and sustained PG ≥ 3.9 mmol/l for 2 hr after the bolus. PG response to glucagon declined with increasing insulin levels. The glucagon dose to optimally treat mild hypoglycaemia depended exponentially on insulin levels, regardless of how insulin was estimated. A 125‐μg glucagon dose was needed to optimally treat mild hypoglycaemia when insulin levels were equal to baseline levels. In contrast, glucagon doses >500 μg were needed when se/ba‐insulin >2.5, IOB >2.0 U or IOB/TDD >6%. Although the proposed model‐based glucagon regimen needs confirmation in clinical trials, this is the first attempt to develop an insulin‐dependent glucagon dosing regimen for treatment of insulin‐induced mild hypoglycaemia in patients with type 1 diabetes.     

A validated,sensitive electrophoretic method for the detection of activin receptor type II‐Fc fusion proteins in human blood

New therapeutic proteins that trap circulating members of the transforming growth factor (TGF) beta superfamily (activins and growth differentiation factors) show promising effects on erythropoiesis and muscular growth. They are dimeric recombinant fusion proteins composed of the extracellular domain of a human activin receptor (ActRIIA or IIB) linked to the Fc part of human IgG1. Sotatercept (ActRIIA‐Fc) and Luspatercept (a modified ActRIIB‐Fc) in particular are now in phase 2/3 of clinical trials against anemia and included in the prohibited list established by the World Anti‐Doping Agency. To prevent a potential misuse by athletes in the near future, a robust and sensitive method of detection is needed. We validated an approach adapted from an electrophoretic method used for the detection of recombinant erythropoietins that allowed detection of various ActRIIA‐Fc and ActRIIB‐Fc proteins, including variants produced in different cell types, after a single immuno‐extraction step. After separation by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS‐PAGE), an initial testing procedure performed by single‐blotting can indicate the presence of an ActRII‐Fc (indifferently type IIA or IIB). A confirmation performed by double‐blotting using different antibodies for detection allows a more precise identification of the type of ActRII‐Fc (IIA, IIB). Starting from a few hundred microliters of serum or plasma, this method is specific, sensitive, and easy to perform. It could easily be adopted by anti‐doping laboratories.     

白桦茸不同部位多糖含量比较分析及抗疲劳作用研究

目的 建立白桦茸多糖含量测定方法,比较不同部位多糖含量及抗疲劳作用。方法 采用紫外分光光度法测定比较不同部位多糖含量,小鼠负重力竭游泳实验比较不同部位抗疲劳作用。结果 重复性RSD=1.77%（n=6）,加样回收率为99.93%,RSD=1.96%（n=6）。白桦茸菌肉多糖含量3.18%,外壳含量8.57%。与空白组比较,菌肉与外壳组小鼠负重游泳力竭时间显著延长。结论 该方法准确、简便,可用于白桦茸多糖含量测定。外壳多糖含量显著高于菌肉,白桦茸外壳提升正常小鼠抗疲劳能力较菌肉强。     

红旱莲不同部位金丝桃苷含量测定

目的 比较了红旱莲药材不同部位（茎、叶、花、果）中金丝桃苷的含量差异。方法 采用高效液相色谱法进行测定,采用C₁₈（4.6 mm×250 mm,5 μm）色谱柱,乙腈-0.1%磷酸为流动相,360 nm为检测波长,流速为1.0 mL·min^-1,柱温30 ℃。结果 金丝桃苷的线性范围为2.904～58.08 μg·mL^-1,相关系数r=0.999 8,平均回收率为 95.1%,RSD为1.3%;红旱莲药材不同部位（茎、叶、花、果）中金丝桃苷的含量分别为0.405、3.221、2.260、0.371 mg·g^-1。结论 红旱莲中不同部位中金丝桃苷含量具有显著差异,叶中含量最高。     

天然黄酮类化合物防治糖尿病肾病的研究进展

糖尿病肾病（DN）是一种严重的糖尿病并发症,其发病机制复杂而多样。现代药理研究表明,天然黄酮类化合物具有多种潜在药用价值,对糖尿病肾病的防治作用就是其中之一。黄酮类化合物抗糖尿病肾病的作用机制是多方面药理活性的综合结果,包括通过抗氧化应激与清除自由基、抗炎、改善血糖血脂紊乱、抗凋亡、调节血管舒张及改善血流动力学异常等途径来实现。在查阅近年来国内外发表的相关文献后,对黄酮类化合物在糖尿病肾病防治中的多种作用及相关机制进行综述,以期为糖尿病肾病防治药物的研发提供参考。     

Eucalyptol-based green extraction of brown alga Zonaria tournefortii

A green extraction method, based on the use of 1,8-cineole (eucalyptol) as biosolvent, has been developed to prepare crude extracts from the brown alga Zonaria tournefortii characterized by chemical composition, particularly dominated by phenolic compounds derived from phloroglucinol. The main advantage of the developed technique are the recovery of eucalyptol, based on multistep liquid-liquid extraction with distilled water, followed by centrifugation and elimination of the aqueous phase, and the complete recycling of biosolvent by steam distillation. A comparative study between the proposed green extract and the conventional extract, prepared by solvent maceration using the mixture CH₂Cl₂/MeOH (1/1:v/v), was performed in terms of qualitative and quantitative determination of several parameters as:(i) the total phenolic content determined by the Folin-Ciocalteu assay, (ii) the presence of phenols determined by high performance liquid chromatography (HPLC), and (iii) the antioxidant activity assessed by the DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging assay. In short, eucalyptol provides a safe and selective extraction of phenolic compounds from Zonaria tournefortii with no environmental side effects and a good recovery of the solvent.     

Prenatal Maternal Depressive Symptoms Predict Early Infant Health Concerns

Introduction

Recent research suggests that health disparities among low-SES and ethnic minority populations may originate from prenatal and early life exposures. Postpartum maternal depressive symptoms have been linked to poorer infant physical health, yet prenatal depressive symptoms not been thoroughly examined in relation to infant health.

Methods

In a prospective study of low-income Mexican American mothers and their infants, women (N = 322, median age 27.23, IQR = 22.01–32.54) completed surveys during pregnancy (median gestation 39.50, IQR = 38.71–40.14 weeks) and 12 weeks after birth. We investigated (1) if prenatal depressive symptoms predicted infant physical health concerns at 12 weeks of age, (2) whether these associations occurred above and beyond concurrent depressive symptoms, and (3) if birth weight, gestational age, and breastfeeding were mediators of prenatal depression predicting subsequent infant health.

Results

Higher prenatal depressive symptoms were associated with more infant physical health concerns at 12 weeks (p < .001), after accounting for 12-week maternal depressive symptoms, breastfeeding, gestational age, and birth weight. Twelve-week maternal depressive symptoms were concurrently associated with more infant health concerns (p < .01). Birth weight, gestational age, and breastfeeding were not associated with maternal depression or infant health concerns.

Discussion

Results establish a link between prenatal depressive symptoms and an elevated risk of poor health evident shortly after birth. These findings underscore the importance of the prenatal period as a possible sensitive period for infants’ health, and the need for effective interventions for depression during pregnancy to mitigate potentially teratogenic effects on the developing fetus and reduce risks for later health concerns.

     

<Emphasis Type="Italic">Chlamydia trachomatis</Emphasis> and Adverse Pregnancy Outcomes: Meta-analysis of Patients With and Without Infection

Objectives

We conducted a meta-analysis to determine the association between Chlamydia trachomatis and adverse perinatal outcomes.

Methods

Electronic databases were searched between 1970 and 2013. Included studies reported perinatal outcomes in women with and without chlamydia. Summary odds ratios were calculated using fixed- and random-effects models. Study bias was assessed using a Funnel Plot and Begg’s test.

Results

Of 129 articles identified, 56 studies met the inclusion criteria encompassing 614,892 subjects. Chlamydia infection in pregnancy was associated with preterm birth (OR?=?1.27, 95% CI 1.05, 1.54) with a large quantity of heterogeneity (I²?=?61%). This association lost significance when limiting the analysis to high-quality studies based on the Newcastle–Ottawa Scale. Chlamydia infection in pregnancy was also associated with preterm premature rupture of membranes (OR?=?1.81, 95% CI 1.0, 3.29), endometritis (OR 1.69, 95% CI 1.20, 2.38), low birthweight (OR 1.34, 95% CI 1.21, 1.48), small for gestational age (OR 1.14, 95% CI 1.05, 1.25) and intrauterine fetal demise (OR 1.44, 95% CI 1.06, 1.94).

Conclusions

This review provides evidence that chlamydia in pregnancy is associated with a small increase in the odds of multiple adverse pregnancy outcomes. The literature is complicated by heterogeneity and the fact that the association may not hold in higher quality and prospective studies or those that use more contemporary nucleic acid testing.