scholarly journals Hepatic redox state and gluconeogenesis from lactate in vivo in the rat

1973 ◽  
Vol 132 (1) ◽  
pp. 19-25 ◽  
Author(s):  
Richard A. Hawkins ◽  
C. Roger S. Houghton ◽  
Dermot H. Williamson
Keyword(s):  
Redox State ◽  
Inferior Vena ◽  
Lactate Concentration ◽  
Vena Cava ◽  
Dihydroxyacetone Phosphate ◽  
Redox Couples ◽  
Metabolite Concentrations ◽  
Hepatic Redox State

1. To examine the role of the hepatic redox state on the rate of gluconeogenesis the effects of sodium crotonate injection (6mmol/kg body wt.) on rat liver metabolite concentrations and gluconeogenesis from lactate were studied in vivo. 2. Crotonate caused a marked oxidation of cytoplasmic and mitochondrial redox couples; decreases were observed in the ratios of [lactate]/[pyruvate], [glycerol 3-phosphate]/[dihydroxyacetone phosphate], [hydroxybutyrate]/[acetoacetate] and measured [NAD+]/[NADH]. 3. Increases occurred in the liver concentrations of all gluconeogenic intermediates from pyruvate through to glucose 6-phosphate, but there was no change in lactate concentration. 4. To determine whether gluconeogenesis from lactate was altered by the more-oxidized hepatic redox state l-[2-14C]lactic acid was infused into the inferior vena cava (50μmol/min per kg body wt.) and the incorporation of radioactivity into blood glucose was measured. 5. Administration of crotonate transiently decreased the rate of lactate incorporation into glucose but within a few minutes the rate of incorporation returned to that of the controls. 6. The results indicate that in these experiments alteration of the NAD+–NADH systems of cytoplasm and mitochondria to a more-oxidized state did not change the rate of gluconeogenesis.

scholarly journals Endotoxaemia-augmented murine venous thrombosis is dependent on TLR-4 and ICAM-1, and potentiated by neutropenia

2017 ◽  
Vol 117 (02) ◽  
pp. 339-348 ◽  
Author(s):  
Andrea T. Obi ◽  
Elizabeth Andraska ◽  
Yogendra Kanthi ◽  
Chase W. Kessinger ◽  
Megan Elfline ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Inferior Vena ◽  
Leukocyte Adhesion ◽  
Vena Cava ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Supplementary Material ◽  
Pai 1

SummaryVenous thromboembolism is a major cause of death during and immediately post-sepsis. Venous thrombosis (VT) is mediated by cell adhesion molecules and leukocytes, including neutrophil extracellular traps (NETs). Sepsis, or experimentally, endotoxaemia, shares similar characteristics and is modulated via toll like receptor 4 (TLR4). This study was undertaken to determine if endotoxaemia potentiates early stasis thrombogenesis, and secondarily to determine the role of VT TLR4, ICAM-1 and neutrophils (PMNs). Wild-type (WT), ICAM-1-/- and TLR4-/- mice underwent treatment with saline or LPS (10 mg/kg i.p.) alone, or followed by inferior vena cava (IVC) ligation to generate stasis VT. In vivo microscopy of leukocyte trafficking was performed in non-thrombosed mice, and tissue and plasma were harvested during early VT formation. Pre-thrombosis, circulating ICAM-1 was elevated and increased leukocyte adhesion and rolling occurred on the IVC of LPS-treated mice. Post-thrombosis, endotoxaemic mice formed larger, platelet-poor thrombi. Endotoxaemic TLR4-/- mice did not have an augmented thrombotic response and exhibited significantly decreased circulating ICAM-1 compared to endotoxaemic WT controls. Endotoxaemic ICAM-1-/- mice had significantly smaller thrombi compared to controls. Hypothesising that PMNs localised to the inflamed endothelium were promoting thrombosis, PMN depletion using anti-Ly6G antibody was performed. Paradoxically, VT formed without PMNs was amplified, potentially related to endotoxaemia induced elevation of PAI-1 and circulating FXIII, and decreased uPA. Endotoxaemia enhanced early VT occurs in a TLR-4 and ICAM-1 dependent fashion, and is potentiated by neutropenia. ICAM-1 and/or TLR-4 inhibition may be a unique strategy to prevent sepsis-associated VT.Supplementary Material to this article is available online at www.thrombosis-online.com.

scholarly journals Role of Inferior Vena Cava Filter Retrieval in Patients on Chronic Anticoagulation Therapy

2021 ◽  
Vol 23 (2) ◽  
Author(s):  
Savannah Fletcher ◽  
Adam Plotnik ◽  
Ravi N. Srinivasa ◽  
Jeffrey Forris Beecham Chick ◽  
John M. Moriarty
Keyword(s):  
Inferior Vena Cava ◽  
Inferior Vena Cava Filter ◽  
Inferior Vena ◽  
Treatment Options ◽  
Anticoagulation Therapy ◽  
Vena Cava ◽  
Vena Cava Filter ◽  
Venous Thromboembolic

Abstract Purpose of review Describe the role of inferior vena cava filter (IVCF) retrieval in patients on chronic anticoagulation given the overlap of these treatment options in the management of patients with venous thromboembolic disease. Recent findings Despite the increase in IVCF retrievals since the Food and Drug Administration safety communications in 2010 and 2014, retrieval rates remain low. Previous studies have shown that longer filter dwell times are associated with greater risk for filter complications and more difficulty with filter retrievals. Recent findings suggest that complications are more frequent in the first 30 days after placement. Summary The decision to retrieve an optional IVCF is individualized and requires diligent follow-up with consistent re-evaluation of the need for the indwelling IVCF, particularly in those on long-term anticoagulation therapy.

scholarly journals The role of CYP2D in rat brain in methamphetamine-induced striatal dopamine and serotonin release and behavioral sensitization

2021 ◽  
Author(s):  
Marlaina R. Stocco ◽  
Ahmed A. El-Sherbeni ◽  
Bin Zhao ◽  
Maria Novalen ◽  
Rachel F. Tyndale
Keyword(s):  
Neurotransmitter Release ◽  
Behavioral Sensitization ◽  
Serotonin Release ◽  
Striatal Dopamine ◽  
Irreversible Inhibitor ◽  
Drug Concentrations ◽  
Metabolite Concentrations ◽  
The Brain

Abstract Rationale Cytochrome P450 2D (CYP2D) enzymes metabolize many addictive drugs, including methamphetamine. Variable CYP2D metabolism in the brain may alter CNS drug/metabolite concentrations, consequently affecting addiction liability and neuropsychiatric outcomes; components of these can be modeled by behavioral sensitization in rats. Methods To investigate the role of CYP2D in the brain in methamphetamine-induced behavioral sensitization, rats were pretreated centrally with a CYP2D irreversible inhibitor (or vehicle) 20 h prior to each of 7 daily methamphetamine (0.5 mg/kg subcutaneous) injections. In vivo brain microdialysis was used to assess brain drug and metabolite concentrations, and neurotransmitter release. Results CYP2D inhibitor (versus vehicle) pretreatment enhanced methamphetamine-induced stereotypy response sensitization. CYP2D inhibitor pretreatment increased brain methamphetamine concentrations and decreased the brain p-hydroxylation metabolic ratio. With microdialysis conducted on days 1 and 7, CYP2D inhibitor pretreatment exacerbated stereotypy sensitization and enhanced dopamine and serotonin release in the dorsal striatum. Day 1 brain methamphetamine and amphetamine concentrations correlated with dopamine and serotonin release, which in turn correlated with the stereotypy response slope across sessions (i.e., day 1 through day 7), used as a measure of sensitization. Conclusions CYP2D-mediated methamphetamine metabolism in the brain is sufficient to alter behavioral sensitization, brain drug concentrations, and striatal dopamine and serotonin release. Moreover, day 1 methamphetamine-induced neurotransmitter release may be an important predictor of subsequent behavioral sensitization. This suggests the novel contribution of CYP2D in the brain to methamphetamine-induced behavioral sensitization and suggests that the wide variation in human brain CYP2D6 may contribute to differential methamphetamine responses and chronic effects.

Role of right heart receptors in the control of renin, vasopressin, and cortisol secretion in dogs

1992 ◽  
Vol 263 (5) ◽  
pp. R1071-R1077 ◽  
Author(s):  
D. H. Carr ◽  
D. B. Jennings ◽  
T. N. Thrasher ◽  
L. C. Keil ◽  
D. J. Ramsay
Keyword(s):  
Inferior Vena ◽  
Vena Cava ◽  
Plasma Renin ◽  
Atrial Pressure ◽  
Right Atrial ◽  
Right Heart ◽  
Hormonal Responses ◽  
The Right ◽  
Maximal Reduction

We have reported that increased left heart pressure inhibits increases in plasma renin activity (PRA), arginine vasopressin (AVP), and cortisol during arterial hypotension. The goal of this study was to determine whether increases in right heart pressure also inhibited hormonal responses to hypotension. Seven dogs were chronically instrumented with inflatable cuffs around the ascending aorta (AA), the pulmonary artery (PA), and the thoracic inferior vena cava (IVC), as well as with catheters in both atria, the abdominal aorta, and vena cava. The IVC, the PA, and the AA cuffs were inflated on different days to cause step reductions in mean arterial pressure (MAP) of 5, 10, 20, and 30% below control MAP. Graded constriction of the AA caused large increases in left atrial pressure and plasma atrial natriuretic peptide (ANP), but had no effect on plasma AVP or cortisol and caused only a small increase in PRA at the maximal reduction of MAP. Constriction of the IVC reduced both atrial pressures and plasma ANP, but stimulated increases in PRA, AVP, and cortisol. Constriction of the PA increased right atrial pressure and plasma ANP and caused increases in plasma AVP and cortisol that were similar to responses during IVC constriction, but the PRA response was only half (P < 0.05). These results indicate that increasing pressure on the right side of the heart can attenuate the PRA response to hypotension, and suggest that the inhibition is mediated by the rise in plasma ANP.

scholarly journals 5-HT causes splanchnic venodilation

2017 ◽  
Vol 313 (3) ◽  
pp. H676-H686 ◽  
Author(s):  
Bridget M. Seitz ◽  
Hakan S. Orer ◽  
Teresa Krieger-Burke ◽  
Emma S. Darios ◽  
Janice M. Thompson ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Inferior Vena Cava ◽  
Portal Vein ◽  
Superior Mesenteric Vein ◽  
Inferior Vena ◽  
Vena Cava ◽  
Receptor Protein ◽  
Mesenteric Vein

Serotonin [5-hydroxytryptamine (5-HT)] causes relaxation of the isolated superior mesenteric vein, a splanchnic blood vessel, through activation of the 5-HT7 receptor. As part of studies designed to identify the mechanism(s) through which chronic (≥24 h) infusion of 5-HT lowers blood pressure, we tested the hypothesis that 5-HT causes in vitro and in vivo splanchnic venodilation that is 5-HT7 receptor dependent. In tissue baths for measurement of isometric contraction, the portal vein and abdominal inferior vena cava relaxed to 5-HT and the 5-HT1/7 receptor agonist 5-carboxamidotryptamine; relaxation was abolished by the 5-HT7 receptor antagonist SB-269970. Western blot analyses showed that the abdominal inferior vena cava and portal vein express 5-HT7 receptor protein. In contrast, the thoracic vena cava, outside the splanchnic circulation, did not relax to serotonergic agonists and exhibited minimal expression of the 5-HT7 receptor. Male Sprague-Dawley rats with chronically implanted radiotelemetry transmitters underwent repeated ultrasound imaging of abdominal vessels. After baseline imaging, minipumps containing vehicle (saline) or 5-HT (25 μg·kg−1·min−1) were implanted. Twenty-four hours later, venous diameters were increased in rats with 5-HT-infusion (percent increase from baseline: superior mesenteric vein, 17.5 ± 1.9; portal vein, 17.7 ± 1.8; and abdominal inferior vena cava, 46.9 ± 8.0) while arterial pressure was decreased (~13 mmHg). Measures returned to baseline after infusion termination. In a separate group of animals, treatment with SB-269970 (3 mg/kg iv) prevented the splanchnic venodilation and fall in blood pressure during 24 h of 5-HT infusion. Thus, 5-HT causes 5-HT7 receptor-dependent splanchnic venous dilation associated with a fall in blood pressure. NEW & NOTEWORTHY This research is noteworthy because it combines and links, through the 5-HT7 receptor, an in vitro observation (venorelaxation) with in vivo events (venodilation and fall in blood pressure). This supports the idea that splanchnic venodilation plays a role in blood pressure regulation.

scholarly journals In vivo magnetic particle imaging: angiography of inferior vena cava and aorta in rats using newly developed multicore particles

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Azadeh Mohtashamdolatshahi ◽  
Harald Kratz ◽  
Olaf Kosch ◽  
Ralf Hauptmann ◽  
Nicola Stolzenburg ◽  
...  
Keyword(s):  
Image Quality ◽  
Inferior Vena Cava ◽  
Temporal Resolution ◽  
Magnetic Particle ◽  
Inferior Vena ◽  
Vena Cava ◽  
High Temporal Resolution ◽  
Magnetic Particle Imaging ◽  
Particle Imaging

Abstract Magnetic Particle Imaging (MPI) is a new imaging modality, which maps the distribution of magnetic nanoparticles (MNP) in 3D with high temporal resolution. It thus may be suited for cardiovascular imaging. Its sensitivity and spatial resolution critically depend on the magnetic properties of MNP. Therefore, we used novel multicore nanoparticles (MCP 3) for in-vivo MPI in rats and analyzed dose requirements, sensitivity and detail resolution. 8 rats were examined using a preclinical MPI scanner (Bruker Biospin GmbH, Germany) equipped with a separate receive coil. MCP 3 and Resovist were administered intravenously (i.v.) into the rats’ tail veins at doses of 0.1, 0.05 and 0.025 mmol Fe/kg followed by serial MPI acquisition with a temporal resolution of 46 volumes per second. Based on a qualitative visual scoring system MCP 3–MPI images showed a significantly (P ≤ 0.05) higher image quality than Resovist-MPI images. Morphological features such as vessel lumen diameters (DL) of the inferior vena cava (IVC) and abdominal aorta (AA) could be assessed along a 2-cm segment in mesenteric area only after administration of MCP 3 at dosages of 0.1, 0.05 mmol Fe/kg. The mean DL ± SD estimated was 2.7 ± 0.6 mm for IVC and 2.4 ± 0.7 mm for AA. Evaluation of DL of the IVC and AA was not possible in Resovist-MPI images. Our results show, that MCP 3 provide better image quality at a lower dosage than Resovist. MCP 3-MPI with a clinically acceptable dose of 0.05 mmol Fe/kg increased the visibility of vessel lumens compared to Resovist-based MPI towards possible detection of vascular abnormalities such as stenosis or aneurysms, in vivo.

scholarly journals Role of Lung Ultrasound and Inferior Vena Cava Diameter in Assessment of Patients with Heart Failure

2021 ◽  
Vol 85 (2) ◽  
pp. 4102-4107
Author(s):  
Hussein Abd El-Fattah Mohammed ◽  
Mohamed Salah El-Feshawy ◽  
Fareed Shawky Basiony ◽  
Mustafa Abu shady
Keyword(s):  
Heart Failure ◽  
Inferior Vena Cava ◽  
Inferior Vena ◽  
Lung Ultrasound ◽  
Vena Cava ◽  
Patients With Heart Failure ◽  
Inferior Vena Cava Diameter
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