Renal effects induced by prolonged mPGES1 inhibition

2014 ◽  
Vol 306 (1) ◽  
pp. F68-F74 ◽  
Author(s):  
Francisco Salazar ◽  
Michael L. Vazquez ◽  
Jaime L. Masferrer ◽  
Gabriel Mbalaviele ◽  
Maria T. Llinas ◽  
...  
Keyword(s):  
Renal Function ◽  
Plasma Renin ◽  
In Vivo Studies ◽  
Renal Effects ◽  
Excretory Function ◽  
Membrane Bound ◽  
Inflammatory Drugs ◽  
Chronically Instrumented Dogs

The importance of membrane-bound PGE synthase 1 (mPGES1) in the regulation of renal function has been examined in mPGES1-deficient mice or by evaluating changes in its expression. However, it is unknown whether prolonged mPGES1 inhibition induces significant changes of renal function when Na+ intake is normal or low. This study examined the renal effects elicited by a selective mPGES1 inhibitor (PF-458) during 7 days in conscious chronically instrumented dogs with normal Na+ intake (NSI) or low Na+ intake (LSI). Results obtained in both in vitro and in vivo studies have strongly suggested that PF-458 is a selective mPGES1 inhibitor. The administration of 2.4 mg·kg−1·day−1 PF-458 to dogs with LSI did not induce significant changes in renal blood flow (RBF) and glomerular filtration rate (GFR). A larger dose of PF-458 (9.6 mg·kg−1·day−1) reduced RBF ( P < 0.05) but not GFR in dogs with LSI and did not induce changes of renal hemodynamic in dogs with NSI. Both doses of PF-458 elicited a decrease ( P < 0.05) in PGE2 and an increase ( P < 0.05) in 6-keto-PGF1α. The administration of PF-458 did not induce significant changes in renal excretory function, plasma renin activity, and plasma aldosterone and thromboxane B2 concentrations in dogs with LSI or NSI. The results obtained suggest that mPGES1 is involved in the regulation of RBF when Na+ intake is low and that the renal effects elicited by mPGES1 inhibition are modulated by a compensatory increment in PGI2. These results may have some therapeutical implications since it has been shown that prolonged mPGES1 inhibition has lower renal effects than those elicited by nonsteroidal anti-inflammatory drugs or selective cyclooxygenase-2 inhibitors.

Abstract 3751: Selective Improvement of Renal Function in Renovascular Disease by Intra-Renal Infusion of Endothelial Progenitor Cells Restores Myocardial Microvascular Integrity

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Xiangyang Zhu ◽  
Jing Lin ◽  
Kyle Textor ◽  
Alejandro R Chade ◽  
James D Krier ◽  
...  
Keyword(s):  
Renal Function ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Volume Fraction ◽  
Plasma Renin ◽  
In Vivo Studies ◽  
Systemic Hypertension ◽  
Renovascular Disease ◽  
Endothelial Progenitor

Background : Renovascular disease (RVD) and impaired renal function are important risk factors for cardiac disease, but it remained unclear whether selective recovery of renal function can reverse cardiac dysfunction. Aims: This study tested the hypothesis that improvement in renal function using selective intra-renal administration of endothelial progenitor cells (EPC) in swine renovascular hypertension would improve myocardial microvascular (MV) integrity. Methods: The functions of the myocardial MV (response to IV adenosine) and the stenotic kidney of 7 pigs were assessed in-vivo using multi-detector CT after 6 weeks of RVD and hypertension. Autologous EPC expanded in culture were then infused (10x10 6 cells) intra-renally, and in vivo studies repeated 4 wks later. Six normal pigs served as controls. Results : Glomerular filtration rate was lower in RVD compared to normal (47.9±10.1 vs. 70.8±4.3 mL/min, p<0.05) and improved after EPC (to 62.7±1.5 mL/min, p=NS vs. normal), as did renal blood flow. Mean arterial pressure remained elevated after EPC (120.7±11 and 129.4±6 vs. 99.9±4.7 mmHg in normal, p<0.05), and plasma renin activity was unchanged. Myocardial MV permeability-surface area increased in RVD in response to adenosine (0.009±0.001 to 0.011±0.002 AU, p=0.01), while MV volume fraction decreased (4.3±0.8 to 2.7±0.6%, p=0.01), indicating impaired MV barrier function and integrity. Contrarily, both remained unchanged in response to adenosine 4 wks after EPC (0.01±0.002 to 0.01±0.002 AU, p=0.24, and 3.5±0.8 to 3.4±0.5%, p=0.46, respectively), as did normal MV. Conclusion : A single intra-renal infusion of EPC that improved renal function in experimental RVD also preserved remote myocardial MV function, despite sustained systemic hypertension. These findings underscore the cross talk between renal and cardiac function, and the potential of selective renal EPC intervention to preserve both the kidney and heart in RVD. Renal and myocardial microvascular function change in normal and RVD before and after EPC treatment

scholarly journals Chitosan/Pluronic F127 Thermosensitive Hydrogel as an Injectable Dexamethasone Delivery Carrier

Gels ◽  
2022 ◽  
Vol 8 (1) ◽  
pp. 44
Author(s):  
Jomarien García-Couce ◽  
Miriela Tomás ◽  
Gastón Fuentes ◽  
Ivo Que ◽  
Amisel Almirall ◽  
...  
Keyword(s):  
Crosslinking Agent ◽  
Pluronic F127 ◽  
In Vivo Studies ◽  
Thermosensitive Hydrogel ◽  
Fluorescent Compound ◽  
Thermosensitive Hydrogels ◽  
Delivery Platform ◽  
Inflammatory Drugs

Intra-articular administration of anti-inflammatory drugs is a strategy that allows localized action on damaged articular cartilage and reduces the side effects associated with systemic drug administration. The objective of this work is to prepare injectable thermosensitive hydrogels for the long-term application of dexamethasone. The hydrogels were prepared by mixing chitosan (CS) and Pluronic-F127 (PF) physically. In addition, tripolyphosphate (TPP) was used as a crosslinking agent. Chitosan added to the mix increased the gel time compared to the pluronic gel alone. The incorporation of TPP into the material modified the morphology of the hydrogels formed. Subsequently, MTS and Live/Dead® experiments were performed to investigate the toxicity of hydrogels against human chondrocytes. The in vitro releases of dexamethasone (DMT) from CS-PF and CS-PF-TPP gels had an initial burst and took more time than that from the PF hydrogel. In vivo studies showed that hydrogels retained the fluorescent compound longer in the joint than when administered in PBS alone. These results suggest that the CS-PF and CS-PF-TPP hydrogels loaded with DMT could be a promising drug delivery platform for the treatment of osteoarthritis.

scholarly journals Impact of anesthesia and analgesia techniques on glioblastoma progression. A narrative review

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Ann Privorotskiy ◽  
Shreyas P Bhavsar ◽  
Frederick F Lang ◽  
Jian Hu ◽  
Juan P Cata
Keyword(s):  
Patient Outcomes ◽  
Clinical Studies ◽  
Narrative Review ◽  
In Vivo Studies ◽  
General Anesthetics ◽  
Anesthetic Care ◽  
Inflammatory Drugs ◽  
Cox 2 Inhibitors

Abstract Glioblastoma (GBM) is an aggressive malignant CNS tumor with a median survival of 15 months after diagnosis. Standard therapy for GBM includes surgical resection, radiation, and temozolomide. Recently, anesthetics and analgesics have received attention for their potential involvement in mediating tumor growth. This narrative review investigated whether various members of the 2 aforementioned classes of drugs have a definitive impact on GBM progression by summarizing pertinent in vitro, in vivo, and clinical studies. Recent publications regarding general anesthetics have been inconsistent, showing that they can be pro-tumoral or antitumoral depending on the experimental context. The local anesthetic lidocaine has shown consistent antitumoral effects in vitro. Clinical studies looking at anesthetics have not concluded that their use improves patient outcomes. In vitro and in vivo studies looking at opioid involvement in GBM have demonstrated inconsistent findings regarding whether these drugs are pro-tumoral or antitumoral. Nonsteroidal anti-inflammatory drugs, and specifically COX-2 inhibitors, have shown inconsistent findings across multiple studies looking at whether they are beneficial in halting GBM progression. Until multiple repeatable studies show that anesthetics and analgesics can suppress GBM growth, there is no strong evidence to recommend changes in the anesthetic care of these patients.

In vitro and in vivo studies of new cationic Zn(II)‐benzonaphthoporphyrazines as photosensitizers for PDT

2001 ◽  
Vol 5 (8) ◽  
pp. 645-651
Author(s):  
M. Peeva ◽  
M. Shopova ◽  
U. Michelsen ◽  
D. Wöhrle ◽  
G. Petrov ◽  
...  
Keyword(s):  
In Vivo Studies

Effect of caffeine on theophyliine on cerebral blood flow response to brain activation: In vitro and in vivo studies

2005 ◽  
Vol 25 (1_suppl) ◽  
pp. S198-S198
Author(s):  
Joseph R Meno ◽  
Thien-son K Nguyen ◽  
Elise M Jensen ◽  
G Alexander West ◽  
Leonid Groysman ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Brain Activation ◽  
In Vivo Studies ◽  
Blood Flow Response ◽  
Flow Response

Effects of Unfractionated and Low Molecular Weight Heparins on Platelet Thromboxane Biosynthesis “In Vivo”

1994 ◽  
Vol 72 (06) ◽  
pp. 942-946 ◽  
Author(s):  
Raffaele Landolfi ◽  
Erica De Candia ◽  
Bianca Rocca ◽  
Giovanni Ciabattoni ◽  
Armando Antinori ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Unfractionated Heparin ◽  
Low Molecular Weight Heparin ◽  
Primary Source ◽  
In Vivo Studies ◽  
Low Molecular Weight ◽  
Heparin Administration ◽  
To Receive

SummarySeveral “in vitro” and “in vivo” studies indicate that heparin administration may affect platelet function. In this study we investigated the effects of prophylactic heparin on thromboxane (Tx)A2 biosynthesis “in vivo”, as assessed by the urinary excretion of major enzymatic metabolites 11-dehydro-TxB2 and 2,3-dinor-TxB2. Twenty-four patients who were candidates for cholecystectomy because of uncomplicated lithiasis were randomly assigned to receive placebo, unfractionated heparin, low molecular weight heparin or unfractionaed heparin plus 100 mg aspirin. Measurements of daily excretion of Tx metabolites were performed before and during the treatment. In the groups assigned to placebo and to low molecular weight heparin there was no statistically significant modification of Tx metabolite excretion while patients receiving unfractionated heparin had a significant increase of both metabolites (11-dehydro-TxB2: 3844 ± 1388 vs 2092 ±777, p <0.05; 2,3-dinor-TxB2: 2737 ± 808 vs 1535 ± 771 pg/mg creatinine, p <0.05). In patients randomized to receive low-dose aspirin plus unfractionated heparin the excretion of the two metabolites was largely suppressed thus suggesting that platelets are the primary source of enhanced thromboxane biosynthesis associated with heparin administration. These data indicate that unfractionated heparin causes platelet activation “in vivo” and suggest that the use of low molecular weight heparin may avoid this complication.

Half-Life of Platelet Factor 4 (PF-4) in Plasma and Platelets from Macaca Mulatta

1977 ◽  
Vol 37 (01) ◽  
pp. 073-080 ◽  
Author(s):  
Knut Gjesdal ◽  
Duncan S. Pepper
Keyword(s):  
Macaca Mulatta ◽  
Half Life ◽  
Human Platelet ◽  
Gel Filtration ◽  
Platelet Factor 4 ◽  
Active Protein ◽  
Platelet Factor ◽  
Membrane Bound

SummaryHuman platelet factor 4 (PF-4) showed a reaction of complete identity with PF-4 from Macaca mulatta when tested against rabbit anti-human-PF-4. Such immunoglobulin was used for quantitative precipitation of in vivo labelled PF-4 in monkey serum. The results suggest that the active protein had an intra-platelet half-life of about 21 hours. In vitro 125I-labelled human PF-4 was injected intravenously into two monkeys and isolated by immuno-precipita-tion from platelet-poor plasma and from platelets disrupted after gel-filtration. Plasma PF-4 was found to have a half-life of 7 to 11 hours. Some of the labelled PF-4 was associated with platelets and this fraction had a rapid initial disappearance rate and a subsequent half-life close to that of plasma PF-4. The results are compatible with the hypothesis that granular PF-4 belongs to a separate compartment, whereas membrane-bound PF-4 and plasma PF-4 may interchange.

Effectiveness of the integration of quercetin, turmeric, and N-acetylcysteine in reducing inflammation and pain associated with endometriosis. In-vitro and in-vivo studies

2020 ◽  
Vol 72 (5) ◽  
Author(s):  
Mario Fadin ◽  
Maria C. Nicoletti ◽  
Marzia Pellizzato ◽  
Manuela Accardi ◽  
Maria G. Baietti ◽  
...  
Keyword(s):  
In Vivo Studies
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