Influence of venous emptying on the reactive hyperemic blood flow response

Background

Previous research indicates that venous emptying serves as a stimulus for vasodilation in the human forearm. This suggests the importance of recognizing the potential influence of venous volume on reactive hyperemic blood flow (RHBF) following occlusion. The purpose of this study was to examine the influence of venous emptying on forearm vascular function.

Methods

Forearm RHBF, venous capacitance and venous outflow were examined in 35 individuals (age = 22 ± 2 years), using mercury in-Silastic strain gauge plethysmography, at rest and following five minutes of upper arm occlusion using standard procedures (Control). In addition, the same measures were obtained following five minutes of upper arm occlusion preceded by two minutes of passive arm elevation (Pre-elevation).

Results

Average resting arterial inflow was 2.42 ± 1.11 ml·100 ml^-1·min^-1. RHBF and venous capacitance were significantly greater during Pre-elevation compared to Control (RHBF; Pre-elevation: 23.76 ± 5.95 ml·100 ml^-1 ·min^-1 vs. Control: 19.33 ± 4.50; p = 0.001), (venous capacitance; Pre-elevation: 2.74 ± 0.89 % vs. Control: 2.19 ± 0.97, p = 0.001). Venous outflow did not differ between the two conditions.

Conclusion

Venous emptying prior to upper arm occlusion results in a significant greater RHBF response and venous capacitance. Recognition of the influence of venous volume on RHBF is particularly important in studies focusing on arterial inflow, and also provides further evidence for the interplay between the venous and arterial system.

     

Regional changes in reactive hyperemic blood flow during exercise training: time-course adaptations

Background

Few studies have examined the time-course of localized exercise training on regional blood flow in humans. The study examined the influence of handgrip exercise training on forearm reactive hyperemic blood flow and vascular resistance in apparently healthy men.

Methods

Forearm blood flow and vascular resistance were evaluated, in 17 individuals [Age: 22.6 ± 3.5], in both arms, at rest and following 5 minutes of arterial occlusion, using strain gauge plethysmography, prior to training (V1) and every week thereafter (V2-5) for 4 weeks. Handgrip exercise was performed in the non-dominant arm 5 d/wk for 20 minutes at 60% of maximum voluntary contraction, while the dominant arm served as control.

Results

Resting HR, BP, and forearm blood flow and vascular resistance were not altered with training. The trained arm handgrip strength and circumference increased by 14.5% (p = 0.014) and 1.56% (p = 0.03), respectively. ANOVA tests revealed an arms by visit interaction for the trained arm for reactive hyperemic blood flow (p = 0.02) and vascular resistance (p = 0.009). Post-hoc comparison demonstrated increased reactive hyperemic blood flow (p = 0.0013), and decreased post-occlusion vascular resistance (p = 0.05), following the 1^st week of training, with no significant changes in subsequent visits.

Conclusion

The results indicate unilateral improvements in forearm reactive hyperemic blood flow and vascular resistance following 1 week of handgrip exercise training and leveled off for the rest of the study.

     

Optimization of fecal sample preparation for untargeted LC-HRMS based metabolomics

Introduction

Collecting feces is easy. It offers direct outcome to endogenous and microbial metabolites.

Objectives

In a context of lack of consensus about fecal sample preparation, especially in animal species, we developed a robust protocol allowing untargeted LC-HRMS fingerprinting.

Methods

The conditions of extraction (quantity, preparation, solvents, dilutions) were investigated in bovine feces.

Results

A rapid and simple protocol involving feces extraction with methanol (1/3, M/V) followed by centrifugation and a step filtration (10 kDa) was developed.

Conclusion

The workflow generated repeatable and informative fingerprints for robust metabolome characterization.

     

Recurrent posterior circulation infarction caused by anomalous occipital bony process in a young patient

Background

Structural anomaly of the cervical spine or craniocervical junction has been reported as one of the rare causes of ischemic stroke. We report a case of a young patient with recurrent posterior circulation infarction that may have been associated with an anomalous occipital bony process compressing the vertebral artery.

Case presentation

A 23-year-old man experienced recurrent posterior circulation infarction 5 times over a period of 5 years. He had no conventional vascular risk factors. Young age stroke work-up including thorough cardiac, intra- and extracranial vascular evaluation and laboratory tests for the hypercoagulable state or connective tissue disease yielded unremarkable results. An anomalous bony process from the occipital base compressing the left vertebral artery was observed on brain CT. All the recurrent strokes were explainable by the arterial thromboembolism originating from the compressed left vertebral artery. Therefore, the left vertebral artery compressed by the anomalous occipital bony process may have been the culprit behind the recurrent thromboembolic strokes in our patient. Intractable recurrent strokes even under optimal medical treatment led us to make a decision for the intervention. Instead of surgical removal of the anomalous occipital bony process, the left vertebral artery was occluded permanently by endovascular coiling after confirming that this would cause no neurological deficits or flow disturbance in the posterior circulation. There was no recurrence of stroke for 2 years after permanent occlusion of the left vertebral artery.

Conclusion

Arterial thromboembolism originating from the left vertebral artery compressed by the anomalous occipital bony process is a rare but not to be overlooked cause of posterior circulation infarction. When intractable to medical treatment, endovascular occlusion of the vertebral artery without flow disturbance to the posterior circulation may be a useful treatment option when surgical removal is not feasible.

     

Lung injury-induced skeletal muscle wasting in aged mice is linked to alterations in long chain fatty acid metabolism

Introduction

Older patients are more likely to acquire and die from acute respiratory distress syndrome (ARDS) and muscle weakness may be more clinically significant in older persons. Recent data implicate muscle ring finger protein 1 (MuRF1) in lung injury-induced skeletal muscle atrophy in young mice and identify an alternative role for MuRF1 in cardiac metabolism regulation through inhibition of fatty acid oxidation.

Objectives

To develop a model of lung injury-induced muscle wasting in old mice and to evaluate the skeletal muscle metabolomic profile of adult and old acute lung injury (ALI) mice.

Methods

Young (2 month), adult (6 month) and old (20 month) male C57Bl6 J mice underwent Sham (intratracheal H₂O) or ALI [intratracheal E. coli lipopolysaccharide (i.t. LPS)] conditions and muscle functional testing. Metabolomic analysis on gastrocnemius muscle was performed using gas chromatography-mass spectrometry (GC–MS).

Results

Old ALI mice had increased mortality and failed to recover skeletal muscle function compared to adult ALI mice. Muscle MuRF1 expression was increased in old ALI mice at day 3. Non-targeted muscle metabolomics revealed alterations in amino acid biosynthesis and fatty acid metabolism in old ALI mice. Targeted metabolomics of fatty acid intermediates (acyl-carnitines) and amino acids revealed a reduction in long chain acyl-carnitines in old ALI mice.

Conclusion

This study demonstrates age-associated susceptibility to ALI-induced muscle wasting which parallels a metabolomic profile suggestive of altered muscle fatty acid metabolism. MuRF1 activation may contribute to both atrophy and impaired fatty acid oxidation, which may synergistically impair muscle function in old ALI mice.

     

A lost opportunity for science: journals promote data sharing in metabolomics but do not enforce it

Introduction

Data sharing is being increasingly required by journals and has been heralded as a solution to the ‘replication crisis’.

Objectives

(i) Review data sharing policies of journals publishing the most metabolomics papers associated with open data and (ii) compare these journals’ policies to those that publish the most metabolomics papers.

Methods

A PubMed search was used to identify metabolomics papers. Metabolomics data repositories were manually searched for linked publications.

Results

Journals that support data sharing are not necessarily those with the most papers associated to open metabolomics data.

Conclusion

Further efforts are required to improve data sharing in metabolomics.

     

Pseudo current density maps of electrophysiological heart,nerve or brain function and their physical basis

Background

In recent years the visualization of biomagnetic measurement data by so-called pseudo current density maps or Hosaka-Cohen (HC) transformations became popular.

Methods

The physical basis of these intuitive maps is clarified by means of analytically solvable problems.

Results

Examples in magnetocardiography, magnetoencephalography and magnetoneurography demonstrate the usefulness of this method.

Conclusion

Hardware realizations of the HC-transformation and some similar transformations are discussed which could advantageously support cross-platform comparability of biomagnetic measurements.

     

Untargeted metabolomics suffers from incomplete raw data processing

Introduction

Untargeted metabolomics is a powerful tool for biological discoveries. To analyze the complex raw data, significant advances in computational approaches have been made, yet it is not clear how exhaustive and reliable the data analysis results are.

Objectives

Assessment of the quality of raw data processing in untargeted metabolomics.

Methods

Five published untargeted metabolomics studies, were reanalyzed.

Results

Omissions of at least 50 relevant compounds from the original results as well as examples of representative mistakes were reported for each study.

Conclusion

Incomplete raw data processing shows unexplored potential of current and legacy data.

     

Metabolomic profiling of maternal hair suggests rapid development of intrahepatic cholestasis of pregnancy

Introduction

Intrahepatic cholestasis of pregnancy (ICP) is a common maternal liver disease; development can result in devastating consequences, including sudden fetal death and stillbirth. Currently, recognition of ICP only occurs following onset of clinical symptoms.

Objective

Investigate the maternal hair metabolome for predictive biomarkers of ICP.

Methods

The maternal hair metabolome (gestational age of sampling between 17 and 41 weeks) of 38 Chinese women with ICP and 46 pregnant controls was analysed using gas chromatography–mass spectrometry.

Results

Of 105 metabolites detected in hair, none were significantly associated with ICP.

Conclusion

Hair samples represent accumulative environmental exposure over time. Samples collected at the onset of ICP did not reveal any metabolic shifts, suggesting rapid development of the disease.

     

Quantitative analysis of tetrahydrofolate metabolites from <Emphasis Type="Italic">clostridium autoethanogenum</Emphasis>

Introduction

Quantification of tetrahydrofolates (THFs), important metabolites in the Wood–Ljungdahl pathway (WLP) of acetogens, is challenging given their sensitivity to oxygen.

Objective

To develop a simple anaerobic protocol to enable reliable THFs quantification from bioreactors.

Methods

Anaerobic cultures were mixed with anaerobic acetonitrile for extraction. Targeted LC–MS/MS was used for quantification.

Results

Tetrahydrofolates can only be quantified if sampled anaerobically. THF levels showed a strong correlation to acetyl-CoA, the end product of the WLP.

Conclusion

Our method is useful for relative quantification of THFs across different growth conditions. Absolute quantification of THFs requires the use of labelled standards.

     

How the chemical features of molecules may have addressed the settlement of metabolic steps

Introduction

While the evolutionary adaptation of enzymes to their own substrates is a well assessed and rationalized field, how molecules have been originally selected in order to initiate and assemble convenient metabolic pathways is a fascinating, but still debated argument.

Objectives

Aim of the present study is to give a rationale for the preferential selection of specific molecules to generate metabolic pathways.

Methods

The comparison of structural features of molecules, through an inductive methodological approach, offer a reading key to cautiously propose a determining factor for their metabolic recruitment.

Results

Starting with some commonplaces occurring in the structural representation of relevant carbohydrates, such as glucose, fructose and ribose, arguments are presented in associating stable structural determinants of these molecules and their peculiar occurrence in metabolic pathways.

Conclusions

Among other possible factors, the reliability of the structural asset of a molecule may be relevant or its selection among structurally and, a priori, functionally similar molecules.

     

Minimal variation of the plasma lipidome after delayed processing of neonatal cord blood

Background

Cord blood lipids are potential disease biomarkers. We aimed to determine if their concentrations were affected by delayed blood processing.

Method

Refrigerated cord blood from six healthy newborns was centrifuged every 12 h for 4 days. Plasma lipids were analysed by liquid chromatography/mass spectroscopy.

Results

Of 262 lipids identified, only eight varied significantly over time. These comprised three dihexosylceramides, two phosphatidylserines and two phosphatidylethanolamines whose relative concentrations increased and one sphingomyelin that decreased.

Conclusion

Delay in separation of plasma from refrigerated cord blood has minimal effect overall on the plasma lipidome.

     

A methodology for elucidating regulatory mechanisms leading to changes in lipid profiles

Introduction

It is difficult to elucidate the metabolic and regulatory factors causing lipidome perturbations.

Objectives

This work simplifies this process.

Methods

A method has been developed to query an online holistic lipid metabolic network (of 7923 metabolites) to extract the pathways that connect the input list of lipids.

Results

The output enables pathway visualisation and the querying of other databases to identify potential regulators. When used to a study a plasma lipidome dataset of polycystic ovary syndrome, 14 enzymes were identified, of which 3 are linked to ELAVL1—an mRNA stabiliser.

Conclusion

This method provides a simplified approach to identifying potential regulators causing lipid-profile perturbations.

     

KniMet: a pipeline for the processing of chromatography–mass spectrometry metabolomics data

Introduction

Data processing is one of the biggest problems in metabolomics, given the high number of samples analyzed and the need of multiple software packages for each step of the processing workflow.

Objectives

Merge in the same platform the steps required for metabolomics data processing.

Methods

KniMet is a workflow for the processing of mass spectrometry-metabolomics data based on the KNIME Analytics platform.

Results

The approach includes key steps to follow in metabolomics data processing: feature filtering, missing value imputation, normalization, batch correction and annotation.

Conclusion

KniMet provides the user with a local, modular and customizable workflow for the processing of both GC–MS and LC–MS open profiling data.

     

Monitoring spatial and temporal metabolic dynamics of woody poplar root under mechanical stress conditions by NMR-based metabolomics

Introduction

Molecular factors are differentially observed in various bent sectors of poplar (Populus nigra) woody taproots. Responses to stress are modulated by a complex interplay among different hormones and signal transduction pathways. In recent years, metabolomics has been recognized as a powerful tool to characterize metabolic network regulation, and it has been widely applied to investigate plant responses to biotic and abiotic stresses.

Objectives

In this paper we used metabolomics to understand if long term-bending stress induces a “spatial” and a “temporal” metabolic reprogramming in woody poplar roots.

Methods

By NMR spectroscopy and statistical analysis we investigated the unstressed and three portions of stressed root (above-bent, bent, and below-bent) sectors collected at 12 (T₀), 13 (T₁) and 14 (T₂) months after stress induction.

Results

The data indicate a clear between-class separation of control and stressed regions, based on the metabolites regulation, during both spatial and temporal changes. We found that taproots, as a consequence of the stress, try to restore homeostasis and normal metabolic fluxes thorough the synthesis and/or accumulation of specific compounds related to mechanical forces distribution along the bent taproot.

Conclusion

The data demonstrate that the impact of mechanical stress on plant biology can efficiently be studied by NMR-based metabolomics.

     

Heterogeneity in arbuscular mycorrhizal fungal communities may contribute to inconsistent plant-soil feedback in a Neotropical forest

Background and aims

Plant-soil feedback may vary across host species and environmental gradients. The relative importance of these biotic versus abiotic drivers of feedback will determine the stability of plant and microbial communities across environments. If plant hosts are the main driver of soil microbial communities, plant-soil feedback may be stable across changing environments. However, if microbial communities vary with environmental gradients, feedback may also vary, limiting its capacity to predict plant distributions.

Methods

We characterized arbuscular mycorrhizal (AM) fungi across tree plantations and a primary Neotropical rainforest. We then performed a plant-soil feedback pot experiment of AM fungi from these plantations on three plant species and related feedback and AM fungal communities in the field.

Results

In the field, temporal and spatial variation in AM fungal composition was similar in magnitude to variation across plant host species. Composition of AM fungi in the pot experiment significantly differed from the field plots. Furthermore, differential feedback was explained by shifts in AM fungal composition only for one plant host species (Hyeronima alchorneoides) in the pot experiment.

Conclusions

Natural AM fungal communities were temporally and spatially heterogeneous and AM fungal communities in the greenhouse did not reflect natural soils. These factors led to heterogeneous and unpredictable feedback responses, which suggests that applying greenhouse derived plant-soil feedback trends to predict plant coexistence in natural systems may be misleading.

     

Metabolic response of porcine colon explants to in vitro infection by <Emphasis Type="Italic">Brachyspira hyodysenteriae</Emphasis>: a leap into disease pathophysiology

Introduction

Swine dysentery caused by Brachyspira hyodysenteriae is a production limiting disease in pig farming. Currently antimicrobial therapy is the only treatment and control method available.

Objective

The aim of this study was to characterize the metabolic response of porcine colon explants to infection by B. hyodysenteriae.

Methods

Porcine colon explants exposed to B. hyodysenteriae were analyzed for histopathological, metabolic and pro-inflammatory gene expression changes.

Results

Significant epithelial necrosis, increased levels of l-citrulline and IL-1α were observed on explants infected with B. hyodysenteriae.

Conclusions

The spirochete induces necrosis in vitro likely through an inflammatory process mediated by IL-1α and NO.

     

Extraction of natural products from bark of <Emphasis Type="Italic">Betula pendula</Emphasis> using ionic liquids

Introduction

Aqueous–methanol mixtures have successfully been applied to extract a broad range of metabolites from plant tissue. However, a certain amount of material remains insoluble.

Objectives

To enlarge the metabolic compendium, two ionic liquids were selected to extract the methanol insoluble part of trunk from Betula pendula.

Methods

The extracted compounds were analyzed by LC/MS and GC/MS.

Results

The results show that 1-butyl-3-methylimidazolium acetate (IL-Ac) predominantly resulted in fatty acids, whereas 1-ethyl-3-methylimidazolium tosylate (IL-Tos) mostly yielded phenolic structures. Interestingly, bark yielded more ionic liquid soluble metabolites compared to interior wood.

Conclusion

From this one can conclude that the application of ionic liquids may expand the metabolic snapshot.

     

Erythropoietin stimulates the coronary collateral development in patients with coronary chronic total occlusion

Objective

Erythropoietin (EPO) improves cardiac function and induces neovascularisation in post-myocardial infarction heart failure. The aim of this study was to analyse the association between the serum erythropoietin level and coronary collateral development in patients with coronary artery disease and chronic total occlusion.

Methods

A total of 168 patients consisting of 117 with coronary artery disease (CAD, (62 with chronic total occlusion (CTO), 55 without CTO)) and 51 with healthy coronary arteries were included in the study. The patients were assigned as coronary artery disease without CTO (group 0), CAD with CTO (group 1: poor collateral development, group 2: good collateral development) and normal coronary arteries (group 3).

Results

There was a significant positive correlation between serum EPO levels and the Rentrop scores in angiography (r = 0.243, p = 0.001). Similarly, a positive correlation was found between serum EPO levels and the Syntax scores (r = 0.253, p = 0.001). Echocardiography revealed a negative correlation between serum EPO levels and the cardiac ejection fraction (r = ?0.210, p = 0.006).

Conclusions

Serum EPO is a useful biomarker for coronary collateral development in patients with CTO.

     

Lean mass mediates the relation between temporal summation of pain and sex in young healthy adults

Background

Previous studies have shown that women experience greater temporal summation (TS) of pain than men using a repetitive thermal stimulus. These studies, however, did not individualize the thermal stimulus to each subject’s thermal pain sensitivity. The aim of this study was to investigate sex differences in TS using an individualized protocol and potential mediators that have been shown to influence TS including physical activity and body composition.

Methods

Fifty young healthy men and women (21 men) participated in the study. Subjects completed TS testing on the right forearm using a repetitive thermal stimulus at a temperature that the subject reported 6/10 pain. Other testing included body composition (lunar iDXA), activity monitoring (Actigraph), and Pain Catastrophizing Scale (PCS).

Results

Women reported greater TS than men (p?=?0.019), and TS was correlated with right arm lean mass (r?=???0.36, p?=?0.01) and magnification subscale of PCS (r?=???0.32, p?=?0.03). Mediation analysis showed a complete mediation for the relation between sex and TS by right arm lean mass (indirect effect = 2.33, 95% BCa CI [0.42, 4.58]) after controlling for the temperature, the magnification subscale of PCS, and the average time spent in moderate to vigorous physical activity.

Conclusion

The results of this study suggest that lean mass is a contributing factor to the sex differences in TS. Future studies should investigate whether interventions that increase lean mass have a positive effect on TS.