scholarly journals Pump-Free Microfluidic Hemofiltration Device

Micromachines ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 992
Author(s):  
Takahiro Ito ◽  
Takashi Ota ◽  
Rei Kono ◽  
Yoshitaka Miyaoka ◽  
Hidetoshi Ishibashi ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Small Molecules ◽  
Ex Vivo ◽  
Small Region ◽  
Transmembrane Pressure ◽  
In Vitro Experiments ◽  
Oncotic Pressure ◽  
Beagle Dogs ◽  
Electrical Components

Hemofiltration removes water and small molecules from the blood via nanoporous filtering membranes. This paper discusses a pump-free hemofiltration device driven by the pressure difference between the artery and the vein. In the design of the filtering device, oncotic pressure needs to be taken into consideration. Transmembrane pressure (TMP) determines the amount and direction of hemofiltration, which is calculated by subtracting the oncotic pressure from the blood pressure. Blood pressure decreases as the channels progress from the inlet to the outlet, while oncotic pressure increases slightly since no protein is removed from the blood to the filtrate in hemofiltration. When TMP is negative, the filtrate returns to the blood, i.e., backfiltration takes place. A small region of the device with negative TMP would thus result in a small amount of or even zero filtrates. First, we investigated this phenomenon using in vitro experiments. We then designed a hemofiltration system taking backfiltration into consideration. We divided the device into two parts. In the first part, the device has channels for the blood and filtrate with a nanoporous membrane. In the second part, the device does not have channels for filtration. This design ensures TMP is always positive in the first part and prevents backfiltration. The concept was verified using in vitro experiments and ex vivo experiments in beagle dogs. Given the simplicity of the device without pumps or electrical components, the proposed pump-free hemofiltration device may prove useful for either implantable or wearable hemofiltration.

scholarly journals Development of a gel dedicated to gel immersion endoscopy

2021 ◽  
Vol 09 (06) ◽  
pp. E918-E924
Author(s):  
Tomonori Yano ◽  
Atsushi Ohata ◽  
Yuji Hiraki ◽  
Makoto Tanaka ◽  
Satoshi Shinozaki ◽  
...  
Keyword(s):  
Electrical Conductivity ◽  
Porcine Model ◽  
Ex Vivo ◽  
In Vitro Experiments ◽  
Efficacy And Safety ◽  
Coagulative Necrosis ◽  
Novel Technique ◽  
In Vivo Experiments

Abstract Backgrounds and study aims Gel immersion endoscopy is a novel technique to secure the visual field during endoscopy. The aim of this study was to develop a dedicated gel for this technique. Methods To identify appropriate viscoelasticity and electrical conductivity, various gels were examined. Based on these results, the dedicated gel “OPF-203” was developed. Efficacy and safety of OPF-203 were evaluated in a porcine model. Results  In vitro experiments showed that a viscosity of 230 to 1900 mPa·s, loss tangent (tanδ) ≤ 0.6, and hardness of 240 to 540 N/cm2 were suitable. Ex vivo experiments showed electrical conductivity ≤ 220 μS/cm is appropriate. In vivo experiments using gastrointestinal bleeding showed that OPF-203 provided clear visualization compared to water. After electrocoagulation of gastric mucosa in OPF-203, severe coagulative necrosis was not observed in the muscularis but limited to the mucosa. Conclusions OPF-203 is useful for gel immersion endoscopy.

Abstract 15751: A New Role of Sox6 in Renin Regulation

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Jose Gomez ◽  
Eric Sum ◽  
Anna Keyte ◽  
Conrad Hodgkinson ◽  
Mary Hutson ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cell Fate ◽  
Kidney Development ◽  
Ex Vivo ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Renin Angiotensin System ◽  
Adult Kidney ◽  
Fold Reduction

Introduction: The renin-angiotensin system (RAS) is an important component of blood pressure regulation in mammals. Renin catalyzes the rate limiting step of RAS, is produced and stored by Juxtaglomerular (JG) cells in the kidney. However, the transcriptional mechanisms that govern the specification of renin expressing cells under normal or pathophysiological conditions remain poorly understood. During blood pressure changes the number of adult renal cells expressing renin increase through a process termed JG recruitment. We found that this process involves differentiation mesenchymal stromal-like cells (MSC) to renin expressing cells. Our aim in this study was to determine new regulators of renin cell fate during kidney development and JG recruitment. Methods: Gene expression profiles of MSC and JG cells were performed with Affymetrix Mouse 430 2.0 array. In vitro assays were performed in adult renal MSCs isolated from C57BL6 Ren1c YFP mice. Renin expression in vitro was induced by treatment with IBMX and Forskolin. MSC were transduced with lentivirus carrying vectors for Sox6, Sox6 shRNA or controls. Ex vivo analysis was performed in embryonic kidneys (14.5 dpc) isolated and transduced with Sox6 or scrambled shRNA, kidneys were then cultured for 4 days and the expression of Sox6 and Renin analyzed by IHC. Results: Data showed that the transcription factor Sox6 is expressed in renin producing cells in the developing kidney (n=4) and in the adult kidney after stimulation that promotes JG recruitment (n=3). Overexpression of Sox6 (n=3, P<0.05) enhanced differentiation of renal MSCs to renin producing cells in vitro , and Sox6 knockdown reduced differentiation of renal MSC to renin producing cells in vitro (6-fold, n=4, P<0.01). Furthermore, knockdown of Sox6 in an ex vivo model of kidney development resulted in a 5-fold reduction in renin expressing cells (n=4, P<0.05). Conclusion: These results support a novel role for Sox6 in the development of renin expressing cells. This may have implications for renal development and physiology, opening new possibilities of addressing questions regarding both developmental and physiological regulation of renin.

Hypotensive effects of the triterpene oleanolic acid for cardiovascular prevention

2020 ◽  
Vol 13 ◽  
Author(s):  
A. Sureda ◽  
M. Monserrat-Mesquida ◽  
S. Pinya ◽  
P. Ferriol ◽  
S. Tejada
Keyword(s):  
Blood Pressure ◽  
Oleanolic Acid ◽  
Ex Vivo ◽  
Biological Activities ◽  
Cardiovascular Prevention ◽  
In Vivo Studies ◽  
Antihypertensive Activity ◽  
In Vitro Tests

Background:: Hypertension is a high prevalent chronic disease worldwide and a major cardiovascular risk factor. Oleanolic acid (3β-hydroxy-olea-12-en-28-oic acid) is a wide distributed bioactive pentacyclic triterpenoid with diverse biological activities such as anti-inflammatory, hepaprotective anti-diabetic or anti-hypertensive. Objective:: The aim of this study was to review and highlight the available data about antihypertensive activity of oleanolic acid and the described mechanisms of action. Method:: Extensive searches were made in the available literature on oleanolic acid and the data investigating its antihypertensive effects were analysed. Results:: Most of research has been performed on animal models of hypertension, ex vivo studies with aortic ring and some in vitro tests with cell cultures, whereas clinical trials are still lacking. Treatment of hypertensive animals with oleanolic acid significantly ameliorated the rise in the systolic blood pressure. In addition, the hypotensive effects of oleanolic acid are also related to a potent diuretic-natriuretic activity and nephroprotection. In vitro studies have characterized the participation of various signalling pathways that modulate the release of vasodilation mediators. Conclusion:: In vitro and in vivo studies suggest that oleanolic acid effectively reduce blood pressure and could be an interesting co-adjuvant to conventional treatment of hypertension.

IN VIVO SELECTIVITY BETWEEN HYPOTENSIVE AND PLATELET ANTIAGGREGATING ACTIONS OF ILOPROST AND PGI2 IN BEAGLE DOGS

1987 ◽  
Author(s):  
F Hermán ◽  
P Hadházy ◽  
K Magyar
Keyword(s):  
Blood Pressure ◽  
Platelet Aggregation ◽  
Arterial Blood Pressure ◽  
Bolus Administration ◽  
Beagle Dogs ◽  
Duration Of Action ◽  
Arterial Blood ◽  
Level Of Significance

Iloprost (Schering A.G.) is a chemically stable derivative of prostacyclin. We compared the hypotensive and antiaggregatory effects of PGI2 and Iloprost. The concentration producing 50% inhibition (IC50) of ADP-induced platelet aggregation in vitro was 0.35±0.15 nmol/1 for PGI2 and 0.56±0.2 nmol/1 for Iloprost (n=5). The in vivo antiaggregatory activity was measured with a modified filtration pressure technique (F.Hermán et al.Thromb. Res.44 /1986/, 575) in anaesthetized beagle dogs; the change in arterial blood pressure was recorded simultaneously. Using this technique, the dose-response relationship and the duration of action of prostacyclin and Iloprost following bolus administration have been determined. PGI2 was equipotent with Iloprost in inhibiting platelet aggregation in vivo (ED25: 0.25±0.04 nmol/kg; 0.28±0.05 respectively). At the same time PGI2 was two times as potent as Iloprost in decreasing the mean arterial blood pressure (ED25: 0.41±0.12 nmol/kg; 0.87±0.14 nmol/kg respectively). The antiaggregatory and hypotensive effects of Iloprost last longer in each experiment than that of PGI2, but did not reach the level of significance probably due to the considerable interindividual differences. The in vivo selectivity ratios (hypotensive potency/antiaggregatory potency) of Iloprost and PGI2 were 0.32 and 0.6 respectively. These results show that in anesthetized beagles Iloprost is somewhat more selective than PGI2 in inhibiting platelet aggregation.

scholarly journals Harnessing the Intrinsic Photochemistry of Isoxazoles for the Development of Chemoproteomic Crosslinking Methods

2021 ◽  
Author(s):  
Marshall G. Lougee ◽  
Vinayak Vishnu Pagar ◽  
Hee Jong Kim ◽  
Samantha X. Pancoe ◽  
Robert H. Mach ◽  
...  
Keyword(s):  
Protein Binding ◽  
Small Molecules ◽  
Functional Groups ◽  
Ex Vivo ◽  
Initial Report ◽  
Biologically Relevant ◽  
Fine Grained ◽  
Wide Range ◽  
Unique Method

Photo-crosslinking is a powerful technique for identifying both coarse- and fine-grained information on protein binding by small molecules. However, the scope of useful functional groups remains limited, with most studies focusing on diazirine, aryl azide, or benzophenone-containing molecules. Here, we report a unique method for photo-crosslinking, employing the intrinsic photochemistry of the isoxazole, a common heterocycle in medicinal chemistry, to offer an alternative to existing strategies using more perturbing, extrinsic crosslinkers. In this initial report, this technique is applied both in vitro and ex vivo, used in a variety of common chemoproteomic workflows, and validated across multiple proteins, demonstrating the utility of isoxazole photo-crosslinking in a wide range of biologically relevant experiments.

scholarly journals Role of ClC-K and barttin in low potassium-induced sodium chloride cotransporter activation and hypertension in mouse kidney

2018 ◽  
Vol 38 (1) ◽  
Author(s):  
Naohiro Nomura ◽  
Wakana Shoda ◽  
Yuanlong Wang ◽  
Shintaro Mandai ◽  
Taisuke Furusho ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Sodium Chloride ◽  
Ex Vivo ◽  
Extracellular Potassium ◽  
Sodium Chloride Cotransporter ◽  
Low Potassium ◽  
Wnk Kinases

The sodium chloride cotransporter (NCC) has been identified as a key molecule regulating potassium balance. The mechanisms of NCC regulation during low extracellular potassium concentrations have been studied in vitro. These studies have shown that hyperpolarization increased chloride efflux, leading to the activation of chloride-sensitive with-no-lysine kinase (WNK) kinases and their downstream molecules, including STE20/SPS1-related proline/alanine-rich kinase (SPAK) and NCC. However, this mechanism was not studied in vivo. Previously, we developed the barttin hypomorphic mouse (Bsndneo/neo mice), expressing very low levels of barttin and ClC-K channels, because barttin is an essential β-subunit of ClC-K. In contrast with Bsnd−/− mice, Bsndneo/neo mice survived to adulthood. In Bsndneo/neo mice, SPAK and NCC activation after consuming a low-potassium diet was clearly impaired compared with that in wild-type (WT) mice. In ex vivo kidney slice experiment, the increase in pNCC and SPAK in low-potassium medium was also impaired in Bsndneo/neo mice. Furthermore, increased blood pressure was observed in WT mice fed a high-salt and low-potassium diet, which was not evident in Bsndneo/neo mice. Thus, our study provides in vivo evidence that, in response to a low-potassium diet, ClC-K and barttin play important roles in the activation of the WNK4-SPAK-NCC cascade and blood pressure regulation.

Abstract MP17: Neuropilin-1 Is A Novel Regulator Of Vascular Tone And Blood Pressure

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Dakshnapriya Balasubbramanian ◽  
George Lambrinos ◽  
Vivian Cristofaro ◽  
Alexander Bigger-Allen ◽  
Beibei Wang ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Cardiac Dysfunction ◽  
Vascular Tone ◽  
Vascular Reactivity ◽  
Ex Vivo ◽  
Neuropilin 1 ◽  
Significant Difference

Introduction: Neuropilin-1 (NRP1) is a transmembrane receptor present in vascular smooth muscle cells (VSMC) that mediates the inhibition of Rho signaling by binding the Class 3 Semaphorin (SEMA) ligand SEMA3A. Hypothesis: We hypothesize that loss of NRP1 in VSMC mitigates SEMA3A-induced Rho inhibition, thereby increasing vascular tone and blood pressure in vivo . Methods: Male and female adult mice (8-12 weeks) with inducible, smooth muscle cell-specific deletion of NRP1 (SM22a-Cre ERT2 X Nrp1 flox/flox ) were examined. Following recombination using 4-hydroxy tamoxifen (SM- NRP1 KO), systolic blood pressure (SBP) was measured using a tail cuff and compared to age- and sex-matched mice that did not receive tamoxifen (control). Aortic vascular reactivity and expression of key proteins in the Rho signaling cascade were measured using ex vivo tension myography and western blotting, respectively. Results: SBP was significantly increased in SM- NRP1 KO mice following recombination compared to control mice (SBP: 136.5 ± 10.9 vs 112.9 ± 5.6 mmHg; p=0.0006). Contractile responses in aortas of SM- NRP1 KO mice to phenylephrine (p=0.025), KCl (p=0.012), and the thromboxane agonist U44619 (p=0.019) were significantly enhanced compared to controls. Expression of total myosin light chain and LIMK-2 proteins were increased in SM- NRP1 KO compared to control aortas. In vitro , treatment of murine primary VSMC expressing NRP1 with SEMA3A decreased angiotensin II-induced Rho-GTP activation. Additionally, control and SM- NRP1 KO mice (starting at 2 weeks post-recombination) were administered angiotensin II (490 ng/kg/day) for 4 weeks. While there was no significant difference in SBP at weeks 1 and 2, SM- NRP1 KO mice had significantly lower SBP at weeks 3 and 4 following angiotensin II infusion compared to controls (Week 4 SBP: 150 ± 1.4 vs 130.5 ± 2.5 mmHg; p=0.02), suggesting a low ejection fraction and cardiac dysfunction in these mice. In support of this observation, mRNA expression of atrial natriuretic peptide was increased in hearts of angiotensin II-infused SM- NRP1 KO mice. Conclusion: Our data suggest that VSMC NRP1 regulates basal tone and blood pressure, and that loss of NRP1 causes hypertension and exacerbates cardiac dysfunction.

Pressor effect of subcutaneous renin in dogs, and effect of reserpine, l-hydrazinophthalazine and hexamethonium on renin hypertension

1959 ◽  
Vol 196 (3) ◽  
pp. 502-506 ◽  
Author(s):  
Florence W. Haynes ◽  
Lewis Dexter
Keyword(s):  
Blood Pressure ◽  
Oral Administration ◽  
Diastolic Blood Pressure ◽  
Pressor Response ◽  
Plasma Renin ◽  
Pressor Effect ◽  
In Vitro Experiments ◽  
Subcutaneous Injections ◽  
Short Series

The pressor effect of series of subcutaneous injections of hog renin was studied in the dog, as well as the modification of the pressor effects of renin by reserpine, hydralazine ( l-hydrazinophthalazine) and hexamethonium. In 22 of 27 experiments, short series of subcutaneous renin injections (1–37 days) in doses of 550–1800 cat units/day were repeatedly followed by moderate elevations of systolic and diastolic blood pressure, whereas control injections of saline, ACTH or extracts of liver were without effect on the blood pressure. In a number of instances, but not in all, a definite increase in plasma renin could be demonstrated during the pressor effect of renin. The pressor effect of subcutaneous renin was still observed during oral administration of reserpine (0.25 mg/day) and hexamethonium (250–500 mg/day) but was often absent during the administration of hydralazine (25 mg/day). The pressor response to intravenous renin was increased in animals receiving reserpine and hexamethonium and decreased after hydralazine. In vitro experiments with these three drugs failed to indicate any significant effect on the formation or destruction of hypertensin.

scholarly journals Partial Agonist Activity of Neonicotinoids on Rat Nicotinic Receptors: Consequences over Epinephrine Secretion and In Vivo Blood Pressure

2021 ◽  
Vol 22 (10) ◽  
pp. 5106
Author(s):  
Joohee Park ◽  
Antoine Taly ◽  
Jennifer Bourreau ◽  
Frédéric De Nardi ◽  
Claire Legendre ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Nervous System ◽  
Nicotinic Acetylcholine Receptors ◽  
Ex Vivo ◽  
Partial Agonist ◽  
Simultaneous Exposure ◽  
Vegetative Nervous System ◽  
Arterial Blood

Neonicotinoid insecticides are nicotine-derived molecules which exert acute neurotoxic effects over the insect central nervous system by activating nicotinic acetylcholine receptors (nAChRs). However, these receptors are also present in the mammalian central and peripheral nervous system, where the effects of neonicotinoids are faintly known. In mammals, cholinergic synapses are crucial for the control of vascular tone, blood pressure and skeletal muscle contraction. We therefore hypothesized that neonicotinoids could affect cholinergic networks in mammals and sought to highlight functional consequences of acute intoxication in rats with sub-lethal concentrations of the highly used acetamiprid (ACE) and clothianidin (CLO). In this view, we characterized their electrophysiological effects on rat α3β4 nAChRs, knowing that it is predominantly expressed in ganglia of the vegetative nervous system and the adrenal medulla, which initiates catecholamine secretion. Both molecules exhibited a weak agonist effect on α3β4 receptors. Accordingly, their influence on epinephrine secretion from rat adrenal glands was also weak at 100 M, but it was stronger at 500 M. Challenging ACE or CLO together with nicotine (NIC) ended up with paradoxical effects on secretion. In addition, we measured the rat arterial blood pressure (ABP) in vivo by arterial catheterization. As expected, NIC induced a significant increase in ABP. ACE and CLO did not affect the ABP in the same conditions. However, simultaneous exposure of rats to both NIC and ACE/CLO promoted an increase of ABP and induced a biphasic response. Modeling the interaction of ACE or CLO on α3β4 nAChR is consistent with a binding site located in the agonist pocket of the receptor. We present a transversal experimental approach of mammal intoxication with neonicotinoids at different scales, including in vitro, ex vivo, in vivo and in silico. It paves the way of the acute and chronic toxicity for this class of insecticides on mammalian organisms

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