scholarly journals Antibiotics Removal by Continuous Venovenous Hemofiltration with a Novel Asymmetric Triacetate Membrane Hemofilter: An in vitro Study

2021 ◽  
pp. 1-7
Author(s):  
Andreas Körtge ◽  
Jolanta Majcher-Peszynska ◽  
Benjamin Heskamp ◽  
Reinhold Wasserkort ◽  
Steffen Mitzner
Keyword(s):  
Plasma Concentrations ◽  
Kidney Injury ◽  
In Vitro Study ◽  
Order Kinetic ◽  
Continuous Venovenous Hemofiltration ◽  
Concentration Data ◽  
Continuous Renal Replacement Therapies ◽  
Sepsis Therapy ◽  
Order Kinetic Model

Introduction: Continuous renal replacement therapies (CRRTs) are essential in the treatment of critically ill patients with acute kidney injury and are also discussed as a supporting sepsis therapy. CRRT can affect antibiotics plasma concentrations. Objective: The effect of continuous venovenous hemofiltration (CVVH) with an asymmetric triacetate (ATA) membrane hemofilter on concentrations of antibiotics with low (meropenem), medium (vancomycin), and high (daptomycin) protein binding (PB) was investigated. Methods: 1 L human whole blood supplemented with antibiotics was recirculated and filtrated for 6 h in vitro. Clearances and sieving coefficients (SC) were determined from antibiotics concentrations measured at filter inlet, outlet, and filtrate side. Reservoir concentration data were fitted using a first-order kinetic model. Results: Meropenem and vancomycin concentrations decreased to 5–10% of the initial plasma level, while only 50% of daptomycin were removed. Clearances and SCs were (10.8 [10.8–17.4] mL/min, SC = 0.72 [0.72–1.16]) for meropenem, (13.4 [12.3–13.7] mL/min, 0.89 [0.82–0.92]) for vancomycin, and (2.1 [1.8–2.1] mL/min, 0.14 [0.12–0.14]) for daptomycin. Removal by adsorption was negligible. Conclusions: The clearances and SCs presented are comparable with findings of other authors. Meropenem and vancomycin, which exhibit low and medium PB, respectively, were strongly removed, while considerably less daptomycin was removed because of its high PB. Our results suggest that in clinical use of the tested antibiotics during CRRT with the ATA hemofilter, the same factors have to be considered for determining the dosing strategy as with filters with other commonly applied membrane materials.

scholarly journals Nephrotoxicity Of Polymyxin B: Experimental Study In Cells And Implications For Nursing Practice

2014 ◽  
Vol 48 (2) ◽  
pp. 272-277 ◽  
Author(s):  
Luciana Barros de Moura Neiva ◽  
Fernanda Teixeira Borges ◽  
Mirian Watanabe ◽  
Edson de Andrade Pessoa ◽  
Dulce Aparecida Barbosa ◽  
...  
Keyword(s):  
Fluorescent Dyes ◽  
Cell Damage ◽  
Kidney Injury ◽  
In Vitro Study ◽  
Polymyxin B ◽  
Concentration Cell ◽  
Tubular Cells ◽  
Risk Patients ◽  
Proximal Tubular

The aim of the study was to characterize the cell damage mechanisms involved in the pathophysiology of cytotoxicity of polymyxin B in proximal tubular cells (LLC - PK1) and discuss about the nurses interventions to identify at risk patients and consider prevention or treatment of nephrotoxicity acute kidney injury. This is a quantitative experimental in vitro study, in which the cells were exposed to 375μM polymyxin B sulfate concentration. Cell viability was determined by exclusion of fluorescent dyes and morphological method with visualization of apoptotic bodies for fluorescence microscopy. Cells exposed to polymyxin B showed reduced viability, increased number of apoptotic cells and a higher concentration of the enzyme lactate dehydrogenase. The administration of polymyxin B in vitro showed the need for actions to minimize adverse effects such as nephrotoxicity.


A Possible Mechanism of Action of 17α-Hydroxyprogesterone Caproate: Enhanced IL-10 Production

2021 ◽  
Author(s):  
Christina J. Megli ◽  
Alisse Hauspurg ◽  
Raman Venkataramanan ◽  
Steve N. Caritis
Keyword(s):  
Mechanism Of Action ◽  
Cytokine Production ◽  
Plasma Concentrations ◽  
In Vitro Study ◽  
Vitro Study ◽  
Clinical Samples ◽  
Omega 3 ◽  
Tnf Α ◽  
Hydroxyprogesterone Caproate

Objective The rate of recurrent spontaneous preterm birth (PTB) was reduced by 33% in the Maternal-Fetal Medicine Unit (MFMU) Network trial of 17α-hydroxyprogesterone caproate (17-OHPC), but the mechanism of action, 17 years later, remains elusive. The robustness of the interleukin-10 (IL-10) response to lipopolysaccharide (LPS) stimulation of leukocytes in pregnant women with a prior PTB correlates with gestational age at delivery. This study sought to determine if there is a relationship between the concentration of 17-OHPC and response to LPS stimulation. Study Design We performed a secondary analysis of data from the Omega-3 MFMU trial which evaluated the effectiveness of omega-3 fatty acid supplementation in reducing recurrent PTB. We utilized previously characterized data from a subanalyses of the Omega-3 trial of IL-10 and tumor necrosis factor alpha (TNF-α) levels from peripheral blood mononuclear cells stimulated with LPS. Blood was obtained from enrolled women at 16 to 22 weeks' gestation (baseline) and 25 to 28 weeks' gestation (posttreatment). All women received 17-OHPC and plasma 17-OHPC concentrations were measured at 25 to 28 weeks' gestation. We analyzed these data to determine if there was a relationship between 17-OHPC concentration and cytokine production. We then performed an in vitro study to determine if 17-OHPC could directly alter cytokine production by THP-1-derived macrophages. Results In the clinical samples, we found that 17-OHPC plasma concentrations were correlated with the quantity of the LPS-stimulated production of IL-10. TNF-α production after LPS stimulation was unrelated to 17-OHPC concentration. In the in vitro study, we demonstrate a 17-OHPC concentration dependent increase in IL-10 production. Conclusion In women receiving 17-OHPC for PTB prevention, we demonstrate a relationship between plasma 17-OHPC and LPS-stimulated IL-10 production by circulating leukocytes. We also demonstrate that, in vitro, 17-OHPC treatment affects IL-10 production by LPS-stimulated macrophages. Collectively, these findings support an immunomodulatory mechanism of action of 17-OHPC in the prevention of recurrent PTB. Key Points

scholarly journals Controlled Release of 5-FU from Chi–DHA Nanoparticles Synthetized with Ionic Gelation Technique: Evaluation of Release Profile Kinetics and Cytotoxicity Effect

2020 ◽  
Vol 11 (3) ◽  
pp. 48
Author(s):  
Mariarosa Ruffo ◽  
Ortensia Ilaria Parisi ◽  
Francesco Patitucci ◽  
Marco Dattilo ◽  
Rocco Malivindi ◽  
...  
Keyword(s):  
Docosahexaenoic Acid ◽  
High Efficiency ◽  
Drug Loading ◽  
In Vitro Release ◽  
Release Profile ◽  
Order Kinetic ◽  
Ionic Gelation ◽  
Cytotoxicity Studies ◽  
Order Kinetic Model

The ionic gelation technique allows us to obtain nanoparticles able to function as carriers for hydrophobic anticancer drugs, such as 5-fluoruracil (5-FU). In this study, reticulated chitosan– docosahexaenoic acid (Chi–DHAr) nanoparticles were synthesized by using a chemical reaction between amine groups of chitosan (Chi) and carboxylic acids of docosahexaenoic acid (DHA) and the presence of a link between Chi and DHA was confirmed by FT-IR, while the size and morphology of the obtained Chi-DHAr nanoparticles was evaluated with dynamic light scattering (DLS) and scanning electron microscopy (SEM), respectively. Drug-loading content (DLC) and drug-loading efficiency (DLE) of 5-FU in Chi-DHAr nanoparticles were 33.74 ± 0.19% and 7.9 ± 0.26%, respectively, while in the non-functionalized nanoparticles (Chir + 5FU), DLC, and DLE were in the ranges of 23.73 ± 0.14%, 5.62%, and 0.23%, respectively. The in vitro release profile, performed in phosphate buffer saline (PBS, pH 7.4) at 37 °C, indicated that the synthetized Chi–DHAr nanoparticles provided a sustained release of 5-FU. Based on the obtained regression coefficient value (R2), the first order kinetic model provided the best fit for both Chir and Chi-DHAr nanoparticles. Finally, cytotoxicity studies of chitosan, 5-FU, Chir, Chir + 5-FU, Chi-DHAr, and Chi-DHAr + 5-FU nanoparticles were conducted. Overall, Chi-DHAr nanoparticles proved to be much more biocompatible than Chir nanoparticles while retaining the ability to release the drug with high efficiency, especially towards specific types of cancerous cells.

scholarly journals Opposite Effects of Single-Dose and Multidose Administration of the Ethanol Extract of Danshen on CYP3A in Healthy Volunteers

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Furong Qiu ◽  
Jian Jiang ◽  
Yueming Ma ◽  
Guangji Wang ◽  
Chenglu Gao ◽  
...  
Keyword(s):  
Single Dose ◽  
Healthy Volunteers ◽  
Plasma Concentrations ◽  
In Vitro Study ◽  
Ethanol Extract ◽  
Tanshinone Iia ◽  
Open Label ◽  
The Mean

The aim of this study was to investigate the effect of single- and multidose administration of the ethanol extract of danshen on in vivo CYP3A activity in healthy volunteers. A sequential, open-label, and three-period pharmacokinetic interaction study design was used based on 12 healthy male individuals. The plasma concentrations of midazolam and its metabolite 1-hydroxymidazolam were measured. Treatment with single dose of the extract caused the meanCmaxof midazolam to increase by 87% compared with control. After 10 days of the danshen extract intake, the mean AUC0–12,Cmax, andt1/2of midazolam were decreased by 79.9%, 66.6%, and 43.8%, respectively. The mean clearance of midazolam was increased by 501.6% compared with control. The in vitro study showed that dihydrotanshinone I in the extract could inhibit CYP3A, while tanshinone IIA and cryptotanshinone could induce CYP3A. In conclusion, a single-dose administration of the danshen extract can inhibit intestinal CYP3A, but multidose administration can induce intestinal and hepatic CYP3A.

scholarly journals Epicatechin limits renal injury by mitochondrial protection in cisplatin nephropathy

2012 ◽  
Vol 303 (9) ◽  
pp. F1264-F1274 ◽  
Author(s):  
Katsuyuki Tanabe ◽  
Yoshifuru Tamura ◽  
Miguel A. Lanaspa ◽  
Makoto Miyazaki ◽  
Norihiko Suzuki ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Kidney Injury ◽  
In Vitro Study ◽  
Protective Effects ◽  
Mitochondrial Fragmentation ◽  
Cytochrome C Release ◽  
Mitochondrial Injury ◽  
Proximal Tubular ◽  
Erk Activity

Cisplatin nephropathy can be regarded as a mitochondrial disease. Intervention to halt such deleterious injury is under investigation. Recently, the flavanol (–)-epicatechin emerges as a novel compound to protect the cardiovascular system, owing in part to mitochondrial protection. Here, we have hypothesized that epicatechin prevents the progression of cisplatin-induced kidney injury by protecting mitochondria. Epicatechin was administered 8 h after cisplatin injury was induced in the mouse kidney. Cisplatin significantly induced renal dysfunction and tubular injury along with an increase in oxidative stress. Mitochondrial damages were also evident as a decrease in loss of mitochondrial mass with a reduction in the oxidative phosphorylation complexes and low levels of MnSOD. The renal damages and mitochondrial injuries were significantly prevented by epicatechin treatment. Consistent with these observations, an in vitro study using cultured mouse proximal tubular cells demonstrated that cisplatin-induced mitochondrial injury, as revealed by a decrease in mitochondrial succinate dehydrogenase activity, an induction of cytochrome c release, mitochondrial fragmentation, and a reduction in complex IV protein, was prevented by epicatechin. Such a protective effect of epicatechin might be attributed to decreased oxidative stress and reduced ERK activity. Finally, we confirmed that epicatechin did not perturb the anticancer effect of cisplatin in HeLa cells. In conclusion, epicatechin exhibits protective effects due in part to its ability to prevent the progression of mitochondrial injury in mouse cisplatin nephropathy. Epicatechin may be a novel option to treat renal disorders associated with mitochondrial dysfunction.

scholarly journals P0540EFFECT OF MEMBRANE MATERIALS ON VANCOMYCIN, TEICOPLANIN AND LINEZOLID REMOVAL DURING CONTINUOUS RENAL REPLACEMENT THERAPIES: AN IN VITRO STUDY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Llaria Godi ◽  
Anna Lorenzin ◽  
Massimo De Cal ◽  
Claudio Ronco
Keyword(s):  
Antimicrobial Agents ◽  
In Vitro Study ◽  
Vitro Study ◽  
Adsorptive Capacity ◽  
Membrane Materials ◽  
Renal Replacement Therapies ◽  
Continuous Renal Replacement Therapies ◽  
Balance Analysis ◽  
Adsorptive Properties

Abstract Background and Aims In a continuous renal replacement therapy (CRRT) scenario, removal of anti-methicillin resistant Staphylococcus Aureus agents can be quantitatively important, thereby contributing to clinically relevant decreases in their plasma concentration during treatment. Extracorporeal elimination of antimicrobial agents is influenced by the dose and modality prescribed, as well as the sieving coefficient (SC) and adsorptive properties of the membrane used.The aim of this study was to document the specific SC and adsorptive capacity of three different membrane materials related to vancomycin, teicoplanin and linezolid. Method This in vitro study used a model of continuous veno-venous hemofiltration. 500 ml of whole blood from healthy donor spiked with one antibiotic under investigation was pumped (blood flow of 50 ml/min and ultrafiltrate flow of 10 ml/min) in a closed-circuit using polysulfone (PS), polymethylmethacrylate (PMMA) and polyacrylonitrile (PAN) membranes. Samples were collected from in-flow, out-flow and ultrafiltrate lines in a 360 min period. Antibiotic concentrations were measured to calculate SCs. Mass balance analysis was assessed to evaluate the adsorptive capacity of PS, PMMA and PAN membrane related to each antibiotic. Results The SCs were substantially affected by the hemodialyzers material in the case of Vancomycin, where PMMA membrane had higher SC (SC=0.89±0.01) compared to PAN (SC=0.79±0.02) and PS (SC=0.62±0.03) membranes. The effect of material was minor for Teicoplanin (Sc=0.12±0.05 for PS, Sc=0.17±0.05 for PMMA, Sc=0.19±0.00 for PAN) and no noticeable difference within hemodialyzers was found for Linezolid (Sc=0.92±0.03 for PS, Sc=0.95±0.01 for PMMA, Sc=0.95±0.00 for PAN). In terms of adsorptive capacity, PS and PMMA membranes showed higher interaction with Vancomycin and Teicoplanin compared with PAN membrane, while a small amount of Linezolid was adsorbed by all the three filters. The cumulative adsorbed amount of PS and PMMA of Teicoplanin were also clinically relevant (99.15 mg/m2 and 51.33 mg/m2 respectively) compared to PAN membrane (9.14 mg/m2). Conclusion PS, PMMA and PAN membranes behave differently in terms of sieving and adsorptive properties related to vancomycin, teicoplanin and linezolid. These differences may have a clinical influence on vancomycin and teicoplanin removal during CRRT, while linezolid variability during CRRT hasn’t to be ascribed for membrane material.

scholarly journals In vitro study on effect of bardoxolone methyl on cisplatin-induced cellular senescence in human proximal tubular cells

2022 ◽  
Author(s):  
Yoshifumi Kurosaki ◽  
Akemi Imoto ◽  
Fumitaka Kawakami ◽  
Motoshi Ouchi ◽  
Asuka Morita ◽  
...  
Keyword(s):  
Cellular Senescence ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
In Vitro Study ◽  
Tunel Staining ◽  
Epithelial Cell Line ◽  
Dependent Manner ◽  
Proximal Tubular ◽  
Induced Apoptosis

AbstractBardoxolone methyl [methyl-2-cyano-3, 12-dioxooleana-1, 9(11)dien-28-oate (CDDO-Me)], an activator of the nuclear factor erythroid-derived 2-related factor2 pathway, is a potential therapeutic candidate for the treatment of kidney diseases. However, its effect against cellular senescence remains unclear. This study aimed to investigate whether CDDO-Me protects cells against cisplatin-induced cellular senescence using an in vitro model. The human renal proximal tubular epithelial cell line HK-2 was treated with cisplatin for 6 h, followed by treatment with or without CDDO-Me (0.1 or 0.2 μmol/L). Senescence markers were analyzed using western blotting and real-time PCR. Apoptosis was evaluated through TUNEL staining. Cisplatin induced changes in the levels of markers specific for proliferation, cell cycle, and senescence in a time- and dose-dependent manner. Furthermore, IL-6 and IL-8 levels in the culture medium increased markedly. These data suggested that cellular senescence-like alterations occurred in HK-2 cells exposed to cisplatin. CDDO-Me treatment reversed the cisplatin-mediated alterations in the levels of cellular senescence markers. The antioxidant enzymes, HO1, NQO1, GPX1, and CAT were upregulated by CDDO-Me treatment. Furthermore, CDDO-Me treatment induced apoptosis in cisplatin-exposed HK-2 cells. Pretreatment with Ac-DEVD-CHO, the caspase inhibitor, suppressed the reversal effect of CDDO-Me against cisplatin-induced cellular senescence-like alterations. This study showed that CDDO-Me attenuated cisplatin-induced premature senescence of HK-2 cells. This beneficial effect may be related to Nrf2 activation. Our findings also showed that CDDO-Me induced apoptosis in cisplatin-treated HK-2 cells, potentially protecting the kidneys from cellular senescence. CDDO-Me appears to be a candidate treatment for acute kidney injury.

Establishment of a first-order kinetic model of light chain-associated amyloid fibril extension in vitro

2002 ◽  
Vol 1601 (1) ◽  
pp. 110-120 ◽  
Author(s):  
Naoki Takahashi ◽  
Kazuhiro Hasegawa ◽  
Itaru Yamaguchi ◽  
Hiromi Okada ◽  
Takanori Ueda ◽  
...  
Keyword(s):  
Kinetic Model ◽  
Light Chain ◽  
Amyloid Fibril ◽  
Order Kinetic ◽  
First Order ◽  
Order Kinetic Model

An alternative solution for α-linolenic acid supplements: in vitro digestive properties of silkworm pupae oil in a pH-stat system

2021 ◽  
Author(s):  
Cheng-Hai Yan ◽  
Xiao-Meng Xun ◽  
Jiao Wang ◽  
Jin-Zheng Wang ◽  
Shuai You ◽  
...  
Keyword(s):  
Kinetic Model ◽  
Pancreatic Lipase ◽  
Order Kinetic ◽  
Lipid Digestion ◽  
First Order ◽  
System P ◽  
Silkworm Pupae ◽  
Order Kinetic Model ◽  
Ph Stat

A brief description of the digestion system in vitro for silkworm pupae oil. Triacylglycerols are hydrolyzed by pancreatic lipase. Meanwhile, the release level and a first-order kinetic model were used to investigate lipid digestion properties.

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