Changes In Plasma Profiles Research Articles

73. Mid-infrared spectroscopy can identify changes in plasma profiles associated with dietary interventions: Untargeted omic screening

73. Mid-infrared spectroscopy can identify changes in plasma profiles associated with dietary interventions: Untargeted omic screening

Immunoprofiling of Nonarteritic Anterior Ischemic Optic Neuropathy.

PurposeNonarteritic anterior ischemic optic neuropathy (NAION) is a common acute optic neuropathy in those older than 50 years. There is no blood diagnostic test or efficient treatment for NAION. We investigated the suitability of blood inflammatory proteins as biomarkers and therapeutic targets of NAION.MethodsWe conducted an exploratory, cross-sectional case-control study including 18 patients with NAION (n = 5 acute, and n = 13 chronic) and 9 controls. NAION was confirmed by clinical examination and optical coherence tomography. Subjects underwent peripheral blood collection; plasma was isolated within 2 hours and analyzed using a 76-plex array of cytokines, chemokines, and growth factors.ResultsIn acute NAION, there was increased peripapillary retinal thickness on optical coherence tomography consistent with optic disc edema. Plasma profiling revealed dramatic changes in inflammatory proteins in NAION. Statistical analysis generated a list of 20 top-ranked molecules in NAION, with 15% overlap in acute and chronic NAION. Principal component analysis, hierarchical clustering, and Spearman correlation generally segregated controls, acute and chronic NAION, with some overlap. Longitudinal data from one patient demonstrated an evolving inflammatory pattern from acute to chronic NAION. In acute NAION, Eotaxin-3, MCP-2, TPO, and TRAIL were the top biomarker candidates. In chronic NAION, IL-1α and CXCL10 emerged as the strongest therapeutic targets.ConclusionsPost-NAION inflammation occurs in both acute and chronic NAION. Statistical analysis of plasma profile changes generated a list of 20 potential biomarker and therapeutic targets of NAION.Translational RelevanceWe identified blood molecular targets to improve NAION diagnosis and treatment.

Inhibition of enteric methanogenesis in dairy cows induces changes in plasma metabolome highlighting metabolic shifts and potential markers of emission

There is scarce information on whether inhibition of rumen methanogenesis induces metabolic changes on the host ruminant. Understanding these possible changes is important for the acceptance of methane-reducing practices by producers. In this study we explored the changes in plasma profiles associated with the reduction of methane emissions. Plasma samples were collected from lactating primiparous Holstein cows fed the same diet with (Treated, n = 12) or without (Control, n = 13) an anti-methanogenic feed additive for six weeks. Daily methane emissions (CH4, g/d) were reduced by 23% in the Treated group with no changes in milk production, feed intake, body weight, and biochemical indicators of health status. Plasma metabolome analyses were performed using untargeted [nuclear magnetic resonance (NMR) and liquid chromatography-mass spectrometry (LC–MS)] and targeted (LC–MS/MS) approaches. We identified 48 discriminant metabolites. Some metabolites mainly of microbial origin such as dimethylsulfone, formic acid and metabolites containing methylated groups like stachydrine, can be related to rumen methanogenesis and can potentially be used as markers. The other discriminant metabolites are produced by the host or have a mixed microbial-host origin. These metabolites, which increased in treated cows, belong to general pathways of amino acids and energy metabolism suggesting a systemic non-negative effect on the animal.

Temporal changes in plasma profile of pregnancy-associated glycoprotein, progesterone and estrone sulfate associated with fetal number during early- and mid-pregnancy in goats

This study was designed to investigate plasma profile of pregnancy-associated glycoprotein (PAG), progesterone (P4) and estrone sulfate (E1S) during early- and mid-pregnancy. The goal was to explore the relationships with values for reproductive variables, to detect the most reliable predictor variable, and to identify the most desirable time point for blood collection for determining fetal number in goats. After ultrasonographic examination at d35–40 post-mating, blood sampling of 15 pregnant goats (total 18) was continued until d114. The PAG profile was characterized by gradual increase during early pregnancy from d26 to d51 and thereafter concentrations were relatively constant until d114 of gestation. The effect of fetal number on plasma PAG, P4 and E1S was first evident on d28, d51 and d26, respectively. During mid-pregnancy, does with twins had a greater (P < 0.05) PAG (S-N = 2.54 ± 0.12 compared with 1.59 ± 0.11), P4 (18.91 ± 0.67 compared with 14.51 ± 0.47 ng/mL) and E1S (16.34 ± 0.76 compared with 11.32 ± 0.44 ng/dL) as compared with does with a singleton fetus. Plasma PAG but not P4 and E1S was positively correlated with fetal number and birth weight of kids during early pregnancy. Multivariate linear regression and discriminant function analyzes allowed for identification of plasma PAG as the most reliable predictor for fetal number and birth weight of kids. Furthermore, d58 was the most suitable single time point for prediction of fetal number using PAG as a biomarker. In conclusion, plasma profile of PAG, P4 and E1S was affected by fetal count. Plasma PAG was identified as the most reliable predictor variable of fetal number and birth weight of kids as compared to plasma P4 and E1S.

Metabolomic and lipidomic plasma profile changes in human participants ascending to Everest Base Camp

At high altitude oxygen delivery to the tissues is impaired leading to oxygen insufficiency (hypoxia). Acclimatisation requires adjustment to tissue metabolism, the details of which remain incompletely understood. Here, metabolic responses to progressive environmental hypoxia were assessed through metabolomic and lipidomic profiling of human plasma taken from 198 human participants before and during an ascent to Everest Base Camp (5,300 m). Aqueous and lipid fractions of plasma were separated and analysed using proton (1H)-nuclear magnetic resonance spectroscopy and direct infusion mass spectrometry, respectively. Bayesian robust hierarchical regression revealed decreasing isoleucine with ascent alongside increasing lactate and decreasing glucose, which may point towards increased glycolytic rate. Changes in the lipid profile with ascent included a decrease in triglycerides (48–50 carbons) associated with de novo lipogenesis, alongside increases in circulating levels of the most abundant free fatty acids (palmitic, linoleic and oleic acids). Together, this may be indicative of fat store mobilisation. This study provides the first broad metabolomic account of progressive exposure to environmental hypobaric hypoxia in healthy humans. Decreased isoleucine is of particular interest as a potential contributor to muscle catabolism observed with exposure to hypoxia at altitude. Substantial changes in lipid metabolism may represent important metabolic responses to sub-acute exposure to environmental hypoxia.

The development and use of a drug-induced immunosuppressed rat-model to screen Phela for mechanism of immune stimulation

Ethnopharmacology relevancyPhela, is code name for a medicinal product made from four South African traditional medicinal plants (Clerodendrum glabrum E. Mey, Polianthes tuberosa (Linn.), Rotheca myricoides (Hochst.) Steane & Mabb. and Senna occidentalis (L.) Link). All these plants have established traditional use in a wide spectrum of diseases. Phela is under development for use as an immune booster in immunocompromised patients, which includes patients with the human immunodeficiency virus (HIV). Already several studies, both pre-clinical and clinical, have shown that Phela is a safe and effective immune booster. Despite some studies on the action of Phela, the mechanism of action by Phela is still not known. Understanding the mechanism of action will enable safer and effective use of the drug for the right indications. Unfortunately, there is no well characterized test-system for screening products for immune stimulant activity. Therefore, the objective of this study was to use Phela as the test article, to develop and validate a rat-model (test system) by which to screen medicines for immune stimulant activity. Material and methodsFirst, the batch of Phela used was authenticated by high performance liquid chromatography (HPLC) techniques; analytical methods for the immunosuppressant drugs, cyclosporine A (CsA), cyclophosphamide (CP) and dexamethasone (Dex) were developed and validated; and a slide-A-Lyzer dialysis was used to test for potential interactions in rat plasma of Phela with CsA, CP and Dex. Thereafter, using Sprague Dawley (SD) rats and in separate experiments, the effective dose of Phela in the study animals was determined in a dose ranging study with levamisole, a known immune stimulant as the positive control; the appropriate doses for immunosuppression by CsA, CP and Dex were determined; the time to reach ‘established immunosuppression’ with each drug was determined (it was also the time for intervention with Phela); and eventually, the effect of Phela on the immune system was tested separately for each drug induced immunosuppression. The immune system was monitored by observing for changes in plasma profiles of IL-2, IL-10, IgG, IgM, CD4 and CD8 cell counts at appropriate intervals, while in addition to function tests, the kidneys, liver, spleen, thymus, were weighed and examined for any pathology. ResultsThe chromatographic fingerprint certified this batch of Phela as similar to the authentic Phela. There was no significant interaction between Phela and CsA, CP and Dex. The effective dose of Phela was determined to be 15.4mg/kg/day. Phela led to a moderate increase in the immune parameters in the normal rats. Co-administration of Phela 15mg/kg/day orally for 21 days with CsA led to stoppage and reversal of the immunosppressive effects of CsA that were exhibited as increased IL-2, IL-10, CD4 and CD8 counts, implying that Phela stimulates the cell mediate immunity (CMI). For CP, Phela led to stoppage and reversal, though moderate, of CP-induced suppression of IL-10, IgM and IgG only, implying that Phela stimulates the humoral immunity (HI) too. Phela had no effect on Dex induced immunosuppression. Stimulation of the CMI means that Phela clinical testing programme should focus on diseases or disorders that compromise the CMI, e.g., HIV and TB. The stimulation of the HI immunity means that Phela may stimulate existing memory cells to produce antibodies. ConclusionThe present study has revealed Phela's mechanism of action as mainly by stimulation of the CMI, implying that the use of Phela as immune booster in HIV patients is appropriate; and that using Phela as the test product, a rat model for screening medicinal products for immune stimulation has been successfully developed and validated, with a hope that it will lead to the testing of other related medicinal products.

EPS05.1 Nutritional formula pre-hydrolyzed by novel point of care lipase device (EFIC™) leads to increased fat absorption in young pigs with exocrine pancreatic insufficiency (EPI)

Background Patients with CF and EPI have difficulty managing weight requiring liquid supplements and tube feeds. Administration of PERTs with enteral feeding is challenging, as enzyme availability is mismatched with formula, negatively affecting fat digestion, absorption and leading to fatty acid deficiencies. EFIC contains an immobilized lipase within a cartridge that is a part of enteral feeding circuit. Formula passes through the EFIC pre-hydrolyzing triglycerides including polyunsaturated fatty acids (PUFA) such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) into absorbable fatty acids. This study measured fat absorption and changes in plasma profiles of DHA and EPA after feeding EPI pigs, with formula +/– EFIC. Methods Fasted EPI pigs were tube fed for 5 h (2 mL/min) with 500 mL Peptamen AF (Nestle, 32 g fat, 1.8 g DHA/EPA), either as EFIC pre-hydrolyzed (EPI+EFIC n = 6) or non-hydrolyzed (EPI n = 5) formula. 3 healthy age matched pigs served as controls. Ten plasma samples were collected over 24 h. Lipids were measured by lipaemic index (LI, turbidometry) and fatty acids by GC-MS and UPLC-MS. Results Fat absorption improved with EFIC compared to the non-hydrolyzed group with 5 h Cmax for LI and AUC 0–10 11.5±1.99 vs. 9.1±1.63 (p Conclusions Use of EFIC leads to an increase in total fat absorption and specifically, plasma levels of physiologically relevant PUFAs, such as DHA and EPA. EFIC provides an effective approach to optimizing fat hydrolysis, PUFA absorption and caloric intake during enteral feeding.

Changes in Plasma Profiles of Matrix Metalloproteinases (MMPs) and Tissue Inhibitors of MMPs in Stress-Induced Cardiomyopathy

BackgroundTransient changes in the composition of the myocardial extracellular matrix may contribute to the ventricular systolic dysfunction in stress-induced cardiomyopathy (SIC). We examined the changes in plasma matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) that occur early after the clinical presentation of SIC. Methods and ResultsTen patients with SIC were enrolled. Plasma concentrations of the 6 major MMPs (1, 2, 3, 7, 8, and 9) and all 4 TIMPs (1, 2, 3, and 4) were analyzed and compared with data from 15 control subjects. Within 24 hours of the clinical presentation, SIC patients had lower MMP-1 levels (0.41 ± 0.13 vs 0.70 ± 0.13 pg/mL; P = .048) and MMP-8 levels (1.61 ± 0.34 vs 4.84 ± 1.38 pg/mL; P = .001) and higher TIMP-4 levels (3.06 ± 0.40 vs 2.16 ± 0.18 pg/mL; P = .05) compared with control. Seven of 9 SIC patients had elevated LV end-diastolic pressures, and all had normal LV end-diastolic dimensions and volumes. ConclusionsPatients afflicted with SIC had MMP and TIMP profiles similar to those described in hypertensive heart disease and diastolic heart failure and different from the profiles following myocardial infarction. Our findings uncovered a unique biomolecular profile in SIC during the first 24 hours of presentation.

Markers of vascular disease in plasma from patients with chronic kidney disease identified by proteomic analysis

Chronic kidney disease (CKD) patients belong to the group of patients with a high prevalence of cardiovascular disease (CVD). Arterial calcification and aortic stiffness are currently used as surrogates for vascular alterations. However, still little is known about prediction and the patho-physiologic mechanisms leading to CVD. We applied capillary electrophoresis coupled mass spectrometry profiling to blood specimens collected from 34 CKD stage 5D patients suffering from vascular alterations to allow insights into the molecular pathology of the disease. Statistical comparison of plasma profiles from mild and severe CVD cases according to either arterial calcification or aortic stiffness unveiled 13 novel biomarkers for vascular disease. Tandem mass spectrometry identified four of these as fragments of collagen alpha-1 type I and III and one as fragment of apolipoprotein CIII. Integrated in a distinct pattern the candidates were validated using the moderate CVD cases among the 34 CKD patients (N=11) and an additional independent blinded cohort of CKD stage 4-5 patients (N=21), who all had not been considered during biomarker discovery. The panel distinguished mild and severe CVD with sensitivity of 89% and specificity of 67% in this independent cohort. This diagnostic phase I/II study supports the notion that vascular alterations are reflected by distinct changes in plasma profiles of CKD patients.

Plasma-Profile Control Using External Circuit in a Capacitively Coupled Plasma Reactor

Very high frequency (VHF) capacitively coupled plasma (CCP) sources offer several benefits, including low plasma potential, high electron density, and controllable dissociation. However, standing electromagnetic waves can make the spatial structure of VHF plasmas a sensitive function of operating conditions and reactor geometry. This paper discusses how the profile of VHF CCPs can be controlled using an external circuit that modifies the electrical boundary conditions. A 2-D plasma model with external circuit has been used for this study, where networks of passive circuit elements can be connected to different electrodes in the reactor. Plasma simulations have been performed for several combinations of capacitors and inductors. It is found that the external circuit can be used to change the radio-frequency current return path, thereby modifying the plasma profile. In general, the plasma is pulled toward the electrode with an inductive impedance and pushed away from the electrode with a capacitive impedance. These changes in plasma profile are related to the relative voltage and their phase on different electrodes.

LIPID PROFILE AND PLASMA ANTIOXIDANT STATUS IN SWEET CARBONATED BEVERAGE-INDUCED METABOLIC SYNDROME IN RATS: PP.34.409

Oxidative stress is involved in the pathophysiology and cardiovascular complications of metabolic syndrome. Objective: To investigate changes in plasma profile of biomarkers of altered redox mechanisms and lipid metabolism, associated with experimentally-induced metabolic syndrome. Methods: Forty-eight male Wistar rats were allowed to drink ad libitum: 1) regular cola (sucrose-sweetened carbonated drink); 2) diet cola (non-nutritive sweetener containing, low-calorie carbonated drink); 3) tap water (controls). After 6 months, all groups were switched to an additional 6 months of tap water drinking (wash-out). Plasma concentrations of the endogenous antioxidants α-tocopherol and ubiquinone-10 were measured using RP-HPLC with UV detection. Plasma concentrations of glucose, triglycerides, total cholesterol and HDL-cholesterol were measured by standard enzymatic methods. Determinations were performed at 6 months (end of treatment) and 12 months (end of wash-out). Results: In group 1, 6 months of sucrose-sweetened beverage drinking led to significant weight gain (7 ± 1%, p < 0.01), hypertension (7.5 ± 0.5% increase in systolic blood pressure, p < 0.01), hypertriglyceridemia (3-fold, p < 0.01), hyperglycemia (15 ± 1%, p < 0.05), and low ubiquinone-10 levels (52 ± 2% decrease, p < 0.05). Light cola-drinking rats showed normoglycemia, but an unexpected tendency to hypertriglyceridemia (2-fold, N.S.) and hypercholesterolemia (29% increase in total cholesterol, N.S.); CoQ10 levels were slightly decreased compared to controls (27%, N.S.), but higher than group 1 (51% increase, N.S). These metabolic alterations reversed after wash-out, except for hypertriglyceridemia and low ubiquinone-10 levels. Interestingly, by this time decreased α-tocopherol concentrations and hypercholesterolemia were observed in all 3 groups (i.e., unrelated to treatment). Conclusions: Experimentally-induced metabolic syndrome induces oxidative stress-related biochemical changes; some of these alterations may be shared by the natural aging process.

Garlic Flavonoids and Organosulfur Compounds: Impact on the Hepatic Pharmacokinetics of Saquinavir and Darunavir

The therapeutic efficacy of saquinavir and darunavir is affected by the presence of xenobiotics (such as garlic compounds) capable of modifying transporter-enzyme interplay. To ascertain the mechanism of interactions between antiretroviral drugs and garlic supplements and to identify the garlic constituents responsible, the hepatic pharmacokinetics of two antiretroviral drugs was investigated in the presence of garlic phytochemicals and aged garlic extract. For this purpose, rat liver slices and isolated rat hepatocytes were used. Aged garlic extract significantly inhibited saquinavir efflux from rat hepatocytes, while the efflux of darunavir significantly increased. Phytochemicals inducing distribution changes of saquinavir and darunavir were most probably flavonoids and lipophilic organosulfur compounds, respectively. All tested phytochemicals (except S-allyl L-cysteine) and aged garlic extract inhibited CYP3A4 metabolism of both drugs and modulated hepatic distribution of the corresponding saquinavir and darunavir metabolites. The competition between saquinavir and garlic constituent(s) for the same binding site on the efflux transporter and the positive cooperative effect between darunavir and garlic phytochemical(s), which bind to separate binding places on transporter, are the most probable mechanisms explaining the plasma profile changes, which could occur in vivo during concomitant consumption of antiretrovirals and garlic supplements.

The influence of different He-Ar ratios on high power CO&lt;SUB align=right&gt;2 laser welding process and weld formation

Pure He is usually used as a plasma blowing gas in high power laser welding because of its high ionisation energy. Its high price however, drives researchers to put more efforts into finding the suitable alternatives. In this paper, 12 mm e-grade shipbuilding steel plates were welded using a 15 KW CO2 laser machine, with the mixture of He and Ar as the blowing gas. The effects of different He-Ar ratios of the blowing gas on laser welding process and weld formation were studied by using a high-speed camera and spectrum was acquired simultaneously. It is found that plasma profile changes with the addition of Ar into He and the spectrum is mainly Fe spectral line even when there are 60% Ar. Sound joints can be obtained even with 40% He + 60% Ar while no acceptable joint formed when using pure Ar.

Molecular genetic and physiologic background of the growth hormone–IGF-I axis in relation to breeding for growth rate and leanness in pigs

The GH–IGF-I axis is of major importance for the regulation of body growth and composition, and cellular proliferation and differentiation processes. Selective breeding aiming to improve growth rate and/or body composition is accompanied by changes of the GH–IGF-I axis. Research aiming to elucidate the genetic and physiologic mechanism(s) underlying these changes may best use single-trait selection lines. Two such pig selection lines, one for growth rate and one for high lean content, were used in experiments to investigate the mechanisms of the GH–IGF-I axis change during selection. This contribution reviews the selection-related changes in the GH–IGF-I axis as the consequences of selection for whole body growth rate or body composition and effects on local tissue growth rate. A model explaining the observed effects and consequences for the pressure on the physiology is presented. In short, selection related demand for GH induces GH synthesis until a limit is reached. After that the pulsatile GH plasma profile changes, which may also affect expression profiles of genes regulating body composition.

Numerical simulation of plasma profile changes in TEXTOR by externally driven radial polarization currents

An improved version of the 2D multifluid code TECXY is used to simulate polarization or biassing experiments on TEXTOR tokamak. In the numerical model the condition of globally ambipolar radial transport in the transition layer is replaced by externally driven radial polarization currents. They are produced by inserting and biassing an electrode with its tip a few centimeters inside the separatrix. The ensuing additional potential drop in the transition layer and the concomitant plasma profile changes are calculated for both signs of polarization. A comparison of modelling results with experimental measurements is presented. The fluid model reproduces some features of the L–H-like transition, but not the locally very high electric fields after bifurcation which are probably related to kinetic effects at very low collisionality.

Short- and long-term dietary effects on female sea bass ( Dicentrarchus labrax): seasonal changes in plasma profiles of lipids and sex steroids in relation to reproduction

Sea bass were fed a natural diet (ND) (trash fish) or two commercial diets ( CD1 = 56% (P)rotein, 11% (L)ipids; CD2 = 47% P, 7% L) during two consecutive reproductive cycles in order to assess the effects on the reproductive performance. CD1 and CD2 had lower energetic and PUFA (polyunsaturated fatty acids) content, especially n-3 fatty acids, with respect to ND. During the first spawning, the levels of sex steriods (17β-estradiol [E2] and testosterone [T], the percentage of good quality (i.e. buoyant) eggs and the hatching rates were similar between the ND and CD1 groups. Females fed CD2 did not show significant variations in E2 or T, and had few spawnings, low egg quality and no egg survival. At second spawning, the fish fed the commercial diets had reduced fecundity and egg viability, together with lower levels of E2 and T, altered patterns of plasma lipids and early presence of atresia in the ovary, with respect to the females fed ND. The present study provides evidence for the importance of dietary lipid for the reproductive processes in the sea bass. The data suggest that long-term dietary deficiences in n-3 fatty acids may affect the patterns of plasma lipids and may induce early gonadal atresia. For example, follicular atresia could reduce the production of gonadal steroids, the fecundity and the subsequent egg survival.

Comparison of the density fluctuation spectrum and amplitude in TEXT with expectations for electron drift waves

Modifications to the spectrum and magnitude of turbulent density fluctuations in the Texas Experimental Tokamak (TEXT) [Plasma Phys. Controlled Fusion 27, 1335 (1985)], measured by far-infrared scattering, are related to changes in plasma profiles (e.g., density and potential) induced by naturally occurring magnetic islands (i.e., m=2) of varying amplitude. The statistical dispersion relation of the microturbulence that propagates in the electron diamagnetic drift direction is observed to be consistent with expectations for electron drift-wave turbulence when a spectral shift due to E×B plasma rotation is included. Observed spectral widths are several times larger than the linear mode frequency. The fluctuation amplitude is found to scale inversely with the electron density scale length.

Effect of Changes in Plasma Profiles on Current Drive by Lower Hybrid Wave in Tokamak

Current drive by applying lower hybrid wave is numerically investigated by using a one dimensional tokamak transport code in order to study effect of changes in plasma profiles on the efficiency of current drive. The efficiency is compared among small, medium, and large tokamaks. It is found that the deposition of wave power moves outwardly due to the increase in the local electron temperature. The efficiency depends on the scale of tokamak. For particularly large tokamak, the average efficiency increases with the width of resonance region in the velocity space of electrons, and reaches up to 1 MA/10 MW.