scholarly journals Changes in Immune Activation during Pregnancy and the Postpartum Period in Treated HIV Infection

2021 ◽  
Author(s):  
Samuel R Schnittman ◽  
Helen Byakwaga ◽  
Yap Boum ◽  
Jerome Kabakyenga ◽  
Lynn T Matthews ◽  
...  
Keyword(s):  
Plasma Volume ◽  
Immune Activation ◽  
Kynurenine Pathway ◽  
Plasma Volume Expansion ◽  
Activation Markers ◽  
Pregnancy And Postpartum ◽  
Tryptophan Catabolism ◽  
Concentration Changes ◽  
Women With Hiv ◽  
D Dimer

Abstract Background Pregnant women with HIV (PWWH) have high postpartum morbidity and mortality from infections like tuberculosis. Immunologic changes during pregnancy and postpartum periods may contribute to these risks, particularly the immunoregulatory kynurenine pathway of tryptophan catabolism, which contributes to both HIV and tuberculosis pathogenesis and increases in the early postpartum. Methods Women with HIV initiating ART in the Uganda AIDS Rural Treatment Outcomes (UARTO) cohort who were pregnant at enrollment or became pregnant during observation were studied (N=54). Plasma kynurenine/tryptophan (KT) ratio, sCD14, sCD163, sCD27, IP-10, D-dimer, IL-6, and I-FABP levels were assessed through the first year of ART and at 3-month intervals throughout pregnancy and one year postpartum. Biomarker changes were assessed with linear mixed models adjusted for ART duration. Hemoglobin concentration changes were used to estimate pregnancy-related changes in plasma volume. Results Median baseline CD4 was 134. D-dimer increased through the third trimester before returning to baseline postpartum while most other biomarkers declined significantly during pregnancy, beyond what would be expected from pregnancy-associated plasma volume expansion. IP-10 and sCD14 remained suppressed for at least 12 months postpartum. KT ratio was the only biomarker that increased above pre-pregnancy baseline in the postpartum (mean +30%, P<0.001) and remained higher than baseline for >9 months (P<0.045 for all timepoints). Conclusions Several immune activation markers decline during pregnancy and remain suppressed postpartum, but the kynurenine pathway of tryptophan catabolism increases above baseline for >9 months postpartum. The mechanisms underlying postpartum kynurenine pathway activity are incompletely understood, but may contribute to increased tuberculosis risk in this setting.

Changes in immune activation markers during pregnancy and postpartum

1999 ◽  
Vol 42 (2) ◽  
pp. 147-165 ◽  
Author(s):  
David N Burns ◽  
Parivash Nourjah ◽  
David J Wright ◽  
Howard Minkoff ◽  
Sheldon Landesman ◽  
...  
Keyword(s):  
Immune Activation ◽  
Activation Markers ◽  
Pregnancy And Postpartum

Capillary Permeability to Macromolecules: Stretched Pore Phenomenon

1957 ◽  
Vol 190 (2) ◽  
pp. 189-193 ◽  
Author(s):  
H. H. Shirley ◽  
C. G. Wolfram ◽  
K. Wasserman ◽  
H. S. Mayerson
Keyword(s):  
Serum Albumin ◽  
Pore Size ◽  
Plasma Volume ◽  
Saline Solution ◽  
Capillary Permeability ◽  
Thoracic Duct Lymph ◽  
Plasma Volume Expansion ◽  
Molecular Weights ◽  
Concentration Changes ◽  
Molecular Weight Fractions

Radioactive iodinated serum albumin and dextran fractions of average molecular weights of 51,000– 255,000 are injected into nembutalized dogs, and concentration changes of these substances are followed in plasma and thoracic and right duct lymphs for 4–6 hours. At this time, when a ‘steady state’ has been established between plasma and lymph, the plasma volumes of the dogs are increased by the infusion of 40 ml/kg of 5% serum albumin in 0.9% saline solution. This results in a significant and striking increase in the concentration of the injected radioactive iodinated albumin and dextrans in right duct and thoracic duct lymph in spite of increased lymph flows. The increase in dextran lymph/plasma concentration ratios occurs with all molecular weight fractions. These results are interpreted as reaffirming our previously formulated concept that infusions producing plasma volume expansion decrease the resistance of the capillary wall to the passage of macromolecules or increase the size of the capillary ‘pores.’ The concept of capillary permeability as a function of ‘pore’ size must, therefore. be modified to include a labile capillary ‘pore’ size, subject to change with variations in plasma volume as well as other factors.

Effects of Long-term Nitric Oxide Synthesis Inhibition on Plasma Volume Expansion and Fetal Growth in the Pregnant Rat

Hypertension ◽  
1995 ◽  
Vol 26 (6) ◽  
pp. 1019-1023 ◽  
Author(s):  
Sofía P. Salas ◽  
Fernando Altermatt ◽  
Mauricio Campos ◽  
Andrea Giacaman ◽  
Pedro Rosso
Keyword(s):  
Nitric Oxide ◽  
Fetal Growth ◽  
Plasma Volume ◽  
Volume Expansion ◽  
Nitric Oxide Synthesis ◽  
Plasma Volume Expansion ◽  
Pregnant Rat ◽  
Synthesis Inhibition

Kinetics of Isotonic and Hypertonic Plasma Volume Expanders

2002 ◽  
Vol 96 (6) ◽  
pp. 1371-1380 ◽  
Author(s):  
Dan Drobin ◽  
Robert G. Hahn
Keyword(s):  
Kinetic Analysis ◽  
Hypertonic Saline ◽  
Plasma Volume ◽  
Dynamic Properties ◽  
Dose Effect ◽  
Plasma Volume Expansion ◽  
Time Curve ◽  
Ringer’S Solution ◽  
Lactated Ringer's Solution ◽  
Infusion Fluids

Background Major differences in plasma volume expansion between infusion fluids are fairly well known, but there is a lack of methods that express their dynamic properties. Therefore, a closer description enabled by kinetic modeling is presented. Methods Ten healthy male volunteers received, on different occasions, a constant-rate intravenous infusion over 30 min consisting of 25 ml/kg of 0.9% saline, lactated Ringer's solution, acetated Ringer's solution, 5 ml/kg of 7.5% saline, or 3 ml/kg of 7.5% saline in 6% dextran. One-, two-, and three-volume kinetic models were fitted to the dilution of the total venous hemoglobin concentration over 240 min. Osmotic fluid shifts were considered when hypertonic fluid was infused. Results All fluids induced plasma dilution, which decreased exponentially after the infusions. The ratio of the area under the dilution-time curve and the infused fluid volume showed the following average plasma-dilution dose-effect (efficiency), using 0.9% saline as the reference (= 1): lactated Ringer's solution, 0.88; acetated Ringer's solution, 0.91; hypertonic saline, 3.97; and hypertonic saline in dextran, 7.22 ("area approach"). Another comparison, based on kinetic analysis and simulation, showed that the strength of the respective fluids to dilute the plasma by 20% within 30 min was 0.94, 0.97, 4.44, and 6.15 ("target dilution approach"). Between-subject variability was approximately half as high for the latter approach. Conclusions The relative efficiency of crystalloid infusion fluids differs depending on whether the entire dilution-time profile or only the maximum dilution is compared. Kinetic analysis and simulation is a useful tool for the study of such differences.

scholarly journals Increased susceptibility of db/db mice to rosiglitazone-induced plasma volume expansion: role of dysregulation of renal water transporters

2013 ◽  
Vol 305 (10) ◽  
pp. F1491-F1497 ◽  
Author(s):  
Li Zhou ◽  
Gang Liu ◽  
Zhanjun Jia ◽  
Kevin T. Yang ◽  
Ying Sun ◽  
...  
Keyword(s):  
Plasma Volume ◽  
Volume Expansion ◽  
Urine Volume ◽  
Plasma Osmolality ◽  
Underlying Mechanism ◽  
Fluid Retention ◽  
Receptor Subtype ◽  
Fluorescent Nanoparticles ◽  
Peroxisome Proliferator ◽  
Plasma Volume Expansion

Thiazolidinediones (TZDs), which are synthetic peroxisome proliferator-activated receptor subtype-γ (PPARγ), agonists are highly effective for treatment of type 2 diabetes. However, the side effect of fluid retention has significantly limited their application. Most of the previous studies addressing TZD-induced fluid retention employed healthy animals. The underlying mechanism of this phenomenon is still incompletely understood, particularly in the setting of disease state. The present study was undertaken to examine rosiglitazone (RGZ)-induced fluid retention in db/db mice and to further investigate the underlying mechanism. In response to RGZ treatment, db/db mice exhibited an accelerated plasma volume expansion as assessed by hematocrit (Hct) and fluorescent nanoparticles, in parallel with a greater increase in body weight, compared with lean controls. In response to RGZ-induced fluid retention, urinary Na+ excretion and urine volume were significantly increased in lean mice. In contrast, the natriuretic and diuretic responses were significantly blunted in db/db mice. RGZ db/db mice exhibited a parallel decrease in plasma Na+ concentration and plasma osmolality, contrasting to unchanged levels in lean controls. Imunoblotting analysis showed downregulation of renal aquaporin (AQP) 2 expression in response to RGZ treatment in lean mice but not in db/db mice. Renal AQP3 protein expression was unaffected by RGZ treatment in lean mice but was elevated in db/db mice. In contrast, the expression of Na+/H+ exchanger-3 (NHE3) and NKCC2 was unchanged in either mouse strain. Together these results suggest that compared with the lean controls, db/db mice exhibited accelerated plasma volume expansion that was in part due to the inappropriate response of renal water transporters.

Exercise stroke volume relative to plasma-volume expansion

1988 ◽  
Vol 64 (1) ◽  
pp. 404-408 ◽  
Author(s):  
M. K. Hopper ◽  
A. R. Coggan ◽  
E. F. Coyle
Keyword(s):  
Stroke Volume ◽  
Plasma Volume ◽  
Volume Expansion ◽  
Peripheral Resistance ◽  
Submaximal Exercise ◽  
Upright Position ◽  
Plasma Volume Expansion ◽  
Trained Subjects ◽  
The Difference ◽  
Dextran Solution

The effects of plasma-volume (PV) expansion on stroke volume (SV) (CO2 rebreathing) during submaximal exercise were determined. Intravenous infusion of 403 +/- 21 ml of a 6% dextran solution before exercise in the upright position increased SV 11% (i.e., 130 +/- 6 to 144 +/- 5 ml; P less than 0.05) in untrained males (n = 7). Further PV expansion (i.e., 706 +/- 43 ml) did not result in a further increase in SV (i.e., 145 +/- 4 ml). SV was somewhat higher during supine compared with upright exercise when blood volume (BV) was normal (i.e., 138 +/- 8 vs. 130 +/- 6 ml; P = 0.08). PV expansion also increased SV during exercise in the supine position (i.e., 138 +/- 8 to 150 +/- 8 ml; P less than 0.05). In contrast to these observations in untrained men, PV expansion of endurance-trained men (n = 10), who were naturally PV expanded, did not increase SV during exercise in the upright or supine positions. When BV in the untrained men was increased to match that of the endurance-trained subjects, SV was observed to be 15% higher (165 +/- 7 vs. 144 +/- 5 ml; P less than 0.05), whereas mean blood pressure and total peripheral resistance were significantly lower (P less than 0.05) in the trained compared with untrained subjects during upright exercise at a similar heart rate. The present findings indicate that exercise SV in untrained men is preload dependent and that increases in exercise SV occur in response to the first 400 ml of PV expansion. It appears that approximately one-half of the difference in SV normally observed between untrained and highly endurance-trained men during upright exercise is due to a suboptimal BV in the untrained men.

TAMI-73. GLIOBLASTOMA CELL POPULATIONS WITH DISTINCT ONCOGENIC PROGRAMS RELEASE PODOPLANIN AS PROCOAGULANT EXTRACELLULAR VESICLES

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi213-vi213
Author(s):  
Nadim Tawil ◽  
Rayhaan Bassawon ◽  
Brian Meehan ◽  
Laura Montermini ◽  
Ali Nehme ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cell Lines ◽  
Extracellular Vesicles ◽  
Glioblastoma Cell ◽  
Activation Markers ◽  
Increased Risk ◽  
Gradient Fractionation ◽  
D Dimer

Abstract BACKGROUND Vascular anomalies, including thrombosis, are a hallmark of glioblastoma (GBM) and an aftermath of dysregulated cancer cell genome and epigenome. Up-regulation of podoplanin (PDPN) by cancer cells has recently been linked to an increased risk of venous thromboembolism in glioblastoma patients. Thus, regulation of this platelet activating protein by transforming events and release from cancer cells is of considerable interest. AIMS I. Investigate the pattern of PDPN expression and characterize PDPN-expressing cellular populations in GBM. II. Evaluate the contribution of oncogenic drivers to PDPN expression in GBM models. III. Investigate the potential involvement of extracellular vesicles (EVs) as a mechanism for systemic dissemination of PDPN and tissue factor (TF). IV. Examine the role of PDPN in intratumoral and systemic thrombosis. METHODS Bioinformatics (single-cell and bulk transcriptome data mining), GBM cell lines and stem cell lines, xenograft models in mice, ELISA assays for PDPN and TF, platelet (PF4) and clotting activation markers (D-dimer), EV electron microscopy, density gradient fractionation, and nano-flow cytometry. RESULTS PDPN is expressed by distinct glioblastoma cell subpopulations (mesenchymal) and downregulated by oncogenic mutations of EGFR and IDH1 genes, via changes in chromatin modifications (EZH2) and DNA methylation, respectively. GBM cells exteriorize PDPN and/or TF as cargo of exosome-like EVs shed both in vitro and in vivo. Injection of glioma PDPN-EVs activates platelets. Increase of platelet activation (PF4) or coagulation markers (D-dimer) occurs in mice harboring the corresponding glioma xenografts expressing PDPN or TF, respectively. Co-expression of PDPN and TF by GBM cells cooperatively increases tumor microthrombosis. CONCLUSION Distinct cellular subsets drive multiple facets of GBM-associated thrombosis and may represent targets for diagnosis and intervention. We suggest that the preponderance of PDPN expression as a risk factor in glioblastoma and the involvement of platelets may merit investigating anti-platelets for potential inclusion in thrombosis management in GBM.

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