Vancomycin Adsorption During in vitro Model of Hemoperfusion with HA380 Cartridge

Nephron ◽  
2021 ◽  
pp. 1-7
Author(s):  
Ilaria Godi ◽  
Anna Lorenzin ◽  
Silvia De Rosa ◽  
Gianlorenzo Golino ◽  
Maira Knust ◽  
...  

<b><i>Introduction:</i></b> A critical point for using blood purification during sepsis may be the potential interaction with antimicrobial therapy, the mainstay of sepsis treatment. The aim of our study was to investigate the vancomycin removal during hemoperfusion (HP) using HA380 cartridge. <b><i>Methods:</i></b> This is an experimental study, in which 500 mL of solution was circulated in a closed-circuit (blood flow of 250 mL/min) simulating HP ran using HA380. Vancomycin was added to reach a through concentration or a very high concentration to evaluate the removal ratio (RR) during 120 min of HP. Comparison between blood-crystalloid solution and balanced solution was performed by using Kruskal-Wallis test. The kinetics of vancomycin removal and the adsorption isotherm were evaluated. <b><i>Results:</i></b> We found a complete removal of vancomycin at baseline through concentration of 23.0 ± 7.4 mg/L. Using extremely high concentration (baseline 777.0 ± 62.2 mg/L), RR was 90.1 ± 0.6% at 5 min and 99.2 ± 0.6% at 120 min. No difference in terms of RR was found between blood-crystalloid mixture and balanced solution. The kinetics of the vancomycin reduction followed an exponential decay. Repeated boluses (total amount of 2,000 mg) resulted in cumulative adsorption of 1,919.4 mg with RR of 96.6 ± 1.4%, regardless of the amount injected (100 vs. 500 mg). Vancomycin adsorption onto HA380 followed the Langmuir isotherm model. <b><i>Conclusions:</i></b> A considerable amount of vancomycin was rapidly removed during in vitro HP with HA380. Clinical studies are needed to determine whether this may lead to underdosing. Drug therapeutic monitoring is highly recommended when using HA380 for blood purification in patients receiving vancomycin.

2018 ◽  
Vol 4 (11) ◽  
pp. eaau8621 ◽  
Author(s):  
Elinor Lazarov ◽  
Melanie Dannemeyer ◽  
Barbara Feulner ◽  
Jörg Enderlein ◽  
Michael J. Gutnick ◽  
...  

Central neurons initiate action potentials (APs) in the axon initial segment (AIS), a compartment characterized by a high concentration of voltage-dependent ion channels and specialized cytoskeletal anchoring proteins arranged in a regular nanoscale pattern. Although the AIS was a key evolutionary innovation in neurons, the functional benefits it confers are not clear. Using a mutation of the AIS cytoskeletal protein βIV-spectrin, we here establish an in vitro model of neurons with a perturbed AIS architecture that retains nanoscale order but loses the ability to maintain a high NaV density. Combining experiments and simulations, we show that a high NaV density in the AIS is not required for axonal AP initiation; it is, however, crucial for a high bandwidth of information encoding and AP timing precision. Our results provide the first experimental demonstration of axonal AP initiation without high axonal channel density and suggest that increasing the bandwidth of the neuronal code and, hence, the computational efficiency of network function, was a major benefit of the evolution of the AIS.


2020 ◽  
Vol 60 (5) ◽  
pp. 659 ◽  
Author(s):  
Gamonmas Dagaew ◽  
Anusorn Cherdthong ◽  
Metha Wanapat ◽  
Pin Chanjula

Context Feeding ruminants with fresh cassava roots (FCR) is limited because they have a high concentration of hydrocyanic acid (HCN). Thus, it was hypothesised that receiving a feed block containing high sulfur (FBS) would reduce hydrocyanic acid (HCN) in FCR and improve rumen fermentation and nutrient digestibility in animals. Aims The goal of the present work was to study the influence of the ratio of FCR to rice straw (RS) together with FBS on kinetics of gas production, HCN concentration, fermentation characteristics and nutrient digestibility, using in vitro technique. Methods The experimental design was a 4 × 2 factorial arrangement in a completely randomised design, with three replications per treatment. Factor A was the FCR to RS ratio, which was 100:0, 60:40, 40:60 or 0:100. Factor B was sulfur, which was provided as two concentrations in FBS (2% and 4% DM). Gas production was recorded after incubation, at 0, 0.5, 1, 2, 4, 6, 8, 12, 18, 24, 48, 72 and 96 h. Fermentation liquor was collected and determined for kinetics of gas production, HCN concentration, fermentation characteristics and nutrient digestibility. Key results Cassava root to RS ratio influenced the cumulative gas production after 96 h. Inclusion of sulfur in the FBS at 4% increased the cumulative gas production, when compared with inclusion at 2%. The gas production from degradable fraction (b) and the rate of gas production (c) were significantly different among the treatments with different FCR:RS ratios, whereas there was no difference between using 2% and 4% sulfur in the FBS. The HCN concentration in fermentation liquor increased with an increasing proportion of FCR. Furthermore, inclusion of sulfur in the feed block at 4% reduced HCN concentration by 42.8%, when compared with inclusion at 2% (P &lt; 0.05). Ammonia-nitrogen concentration was significantly different among the FCR:RS-ratio treatments and was reduced when the proportion of FCR was decreased (P &lt; 0.05). In vitro digestibility was significantly increased with an increasing proportion of FCR. Increasing the proportion of FCR with 4% of sulfur in the FBS significantly increased in vitro DM digestibility, compared with 2% sulfur. Increasing the FCR:RS ratio with 4% of sulfur in the FBS increased the proportion of propionic acid (P &lt; 0.05). Conclusions Using a high FCR:RS ratio (100:0 or 60:40) with 4% sulfur in the FBS enhanced kinetics of gas production, propionic molar proportion, nutrient digestibility, and HCN detoxification by rumen microbes in an in vitro trial. Implications An in vivo study should be encouraged to verify the results and obtain more data.


Dysphagia ◽  
2019 ◽  
Vol 35 (4) ◽  
pp. 685-695 ◽  
Author(s):  
Simmi Patel ◽  
William J. McAuley ◽  
Michael T. Cook ◽  
Yi Sun ◽  
Shaheen Hamdy ◽  
...  

Abstract Drinks and foods may be thickened to improve swallowing safety for dysphagia patients, but the resultant consistencies are not always palatable. Characterising alternative appetising foods is an important task. The study aims to characterise the in vitro swallowing behaviour of specifically formulated thickened dysphagia fluids containing xanthan gum and/or starch with standard jellies and yoghurt using a validated mechanical model, the “Cambridge Throat”. Observing from the side, the model throat can follow an experimental oral transit time (in vitro-OTT) and a bolus length (BL) at the juncture of the pharynx and larynx, to assess the velocity and cohesion of bolus flow. Our results showed that higher thickener concentration produced longer in vitro-OTT and shorter BL. At high concentration (spoon-thick), fluids thickened with starch-based thickener showed significantly longer in vitro-OTT than when xanthan gum-based thickener was used (84.5 s ± 34.5 s and 5.5 s ± 1.6 s, respectively, p < 0.05). In contrast, at low concentration (nectar-like), fluids containing xanthan gum-based thickener demonstrated shorter BL than those of starch-based thickener (6.4 mm ± 0.5 mm and 8.2 mm ± 0.8 mm, respectively, p < 0.05). The jellies and yoghurt had comparable in vitro-OTT and BL to thickeners at high concentrations (honey-like and spoon-thick), indicating similar swallowing characteristics. The in vitro results showed correlation with published in vivo data though the limitations of applying the in vitro swallowing test for dysphagia studies were noted. These findings contribute useful information for designing new thickening agents and selecting alternative and palatable safe-to-swallow foods.


2015 ◽  
Vol 112 (5) ◽  
pp. 1422-1427 ◽  
Author(s):  
E Du ◽  
Monica Diez-Silva ◽  
Gregory J. Kato ◽  
Ming Dao ◽  
Subra Suresh

We developed a microfluidics-based model to quantify cell-level processes modulating the pathophysiology of sickle cell disease (SCD). This in vitro model enabled quantitative investigations of the kinetics of cell sickling, unsickling, and cell rheology. We created short-term and long-term hypoxic conditions to simulate normal and retarded transit scenarios in microvasculature. Using blood samples from 25 SCD patients with sickle hemoglobin (HbS) levels varying from 64 to 90.1%, we investigated how cell biophysical alterations during blood flow correlated with hematological parameters, HbS level, and hydroxyurea (HU) therapy. From these measurements, we identified two severe cases of SCD that were also independently validated as severe from a genotype-based disease severity classification. These results point to the potential of this method as a diagnostic indicator of disease severity. In addition, we investigated the role of cell density in the kinetics of cell sickling. We observed an effect of HU therapy mainly in relatively dense cell populations, and that the sickled fraction increased with cell density. These results lend support to the possibility that the microfluidic platform developed here offers a unique and quantitative approach to assess the kinetic, rheological, and hematological factors involved in vasoocclusive events associated with SCD and to develop alternative diagnostic tools for disease severity to supplement other methods. Such insights may also lead to a better understanding of the pathogenic basis and mechanism of drug response in SCD.


1991 ◽  
Vol 261 (1) ◽  
pp. E31-E40 ◽  
Author(s):  
J. J. Holst ◽  
M. Ehrhart-Bornstein ◽  
T. Messell ◽  
S. S. Poulsen ◽  
H. Harling

We found a high concentration of galanin in extracts of porcine adrenal glands (114 pmol/g). By immunohistochemistry, galanin was localized to groups of medullary cells previously shown to produce norepinephrine. To study mechanisms for the release of galanin, we developed the following in vitro model: isolated perfused porcine adrenals with intact splanchnic nerve supply. When the nerves were electrically stimulated, epinephrine and norepinephrine secretion increased 276- and 291-fold, respectively, and galanin release increased up to 1,300-fold. Acetylcholine at 10(-6) M stimulated galanin release, and hexamethonium almost abolished the response to nerve stimulation. Galanin infusions had no effect on epinephrine and norepinephrine secretion in concentrations of 10(-8) and 10(-7) M, but increased both cortisol and aldosterone secretion (P less than 0.05). Splanchnic nerve stimulation in anesthetized pigs increased the concentration of galanin in the caval vein but not in arterial plasma. It is concluded that galanin, coreleased with catecholamines from the adrenal glands, may have endocrine functions but that galanin may also have local regulatory functions in the adrenals.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Anna Lorenzin ◽  
Llaria Godi ◽  
Massimo De Cal ◽  
Claudio Ronco

Abstract Background and Aims The rationale for blood purification as adjunctive therapy during sepsis involved the capacity in removing endogenous and exogenous toxins, but currently no recommendations exists [1]. A critical point may be the potential interaction with antimicrobial therapy, which remains the mainstay of sepsis treatment. HA330 cartridge (Jafron, Zhuhai City, China), widely used in China and actually available in Europe, is used in hemoperfusion for blood purification in septic patients.The aim of this in vitro study was to investigate the adsorptive capacity of HA330 related to vancomycin (VAN). Reference: 1. Rhodes A et al. Crit Care Med 45:486-552. 2017 Method This is an experimental study, simulating an hemoperfusion treatment with HA330. We circulated (250 ml/min) in a closed loop 500 ml of normal saline solution enriched with VAN, stirred and maintained at 37°C. We spiked 100 mg of VAN every 15 minutes to increase the antibiotic load until reaching 1500 mg, the last injection was 500 mg to get a total amount of 2 g. Samples were collected from the inlet line at each VAN adjunct, after system stabilization. Measured VAN concentrations were used to get the adsorption isotherm: for each VAN load, the adsorbed amount of VAN was obtained by multiplying VAN reduction ratio and the quantity of VAN injected. Results Figure 1 shows VAN adsorption isotherm obtained with HA330 cartridge. We observed that, at each injection, after 15 minutes VAN was almost entirely adsorbed by the cartridge, with an average reduction ratio of 0.96. Interestingly, this was confirmed even adding 500 mg at once. Even increasing the VAN load to 500 mg at once, the reduction ratio was maintained. Conclusion In our study, simulating hemoperfusion using HA330, a rapid and clinically relevant removal of VAN has been shown. A significant amount of VAN (2g) was adsorbed without reaching membrane saturation nor reducing its adsorptive capacity. In a clinical setting, we recommend a therapeutic drug monitoring to optimize VAN levels during blood purification with HA330 and a VAN loading dose may be considered. Further in vivo studies are warranted to confirm these findings.


Molecules ◽  
2011 ◽  
Vol 16 (3) ◽  
pp. 2658-2671 ◽  
Author(s):  
Bojan D. Markovic ◽  
Vladimir D. Dobricic ◽  
Sote M. Vladimirov ◽  
Olivera A. Cudina ◽  
Vladimir M. Savic ◽  
...  

2019 ◽  
Vol 7 (13) ◽  
pp. 2079-2083
Author(s):  
Liudmila Ivanovna Babaskina ◽  
Tatiana Mikhailovna Litvinova ◽  
Dmitrii Vladimirovich Babaskin ◽  
Olga Valerevna Krylova

BACKGROUND: The scientific substantiation for the selection of therapeutically significant dosage of phytocomplex in the dosage form for phonophoresis, control over the delivery of active substances into the body, and what affects this process require the study of the kinetics of phytocomplex flavonoids delivery during phonophoresis. AIM: The aim was to study the possibilities of controlling the process of transdermal delivery of phytocomplex active substances (flavonoids) during phonophoresis in vitro model experiments. METHODS: Working compositions with different concentrations of phytocomplex for phonophoresis were used. The content of flavonoids in the compositions was determined using the spectrophotometric method and was calculated equivalent to quercetin, the flavonoid prevailing in the phytocomplex. The study of the kinetics of flavonoids delivery from working compositions was carried out using Franz diffusion cells and Carbosyl-P membranes. The authors determined the main parameters of the process and established the dependence of the delivery rate of flavonoids on their initial concentration in the working composition. The authors studied the effect of dimethyl sulfoxide and the base-forming substances of the working composition on the kinetics of phytocomplex flavonoid delivery during phonophoresis. RESULTS: The authors recorded an increase in the rate of delivery of the active substances from working compositions containing dimethyl sulfoxide into the model medium by almost 1.5-2 times during the first ten minutes of the experiment (approximate duration of the phonophoresis procedure). The authors proposed technological techniques for improvement of the phonophoresis method for the phytocomplex. The possibilities of control over the process of transdermal delivery of the phytocomplex active ingredients during phonophoresis in vitro model experiments were shown. CONCLUSION: The obtained results provide information for further pharmacological studies of the nature and mechanism of the effect of phytocomplex flavonoids during phonophoresis in the rehabilitation of patients with osteoarthrosis.


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