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1.
Am J Physiol Gastrointest Liver Physiol ; 323(5): G410-G419, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36040119

RESUMO

Disproportionate activation of pattern recognition receptors plays a role in inflammatory bowel disease (IBD) pathophysiology. Diarrhea is a hallmark symptom of IBD, resulting at least in part from an electrolyte imbalance that may be caused by changes in potassium channel activity. We evaluated the impact of Toll-like receptors (TLRs) and nucleotide-binding oligomerization domain 2 (NOD2) stimulation on potassium conductance of the basolateral membrane in human intestinal epithelial cells (IECs) and the role of potassium channels through electrophysiological assays under short-circuit current in Ussing chambers. TLRs and NOD2 were stimulated using specific agonists, and potassium channels were selectively blocked using triarylmethane-34 (TRAM-34), adenylyl-imidodiphosphate (AMP-PNP), and BaCl2. Potassium conductance of the basolateral membrane decreased upon activation of TLR2, TLR4, and TLR7 in T84 cells (means ± SE, -11.2 ± 4.5, -40.4 ± 7.2, and -19.4 ± 5.9, respectively) and in Caco-2 cells (-13.1 ± 5.7, -55.7 ± 7.4, and -29.1 ± 7.2, respectively). In contrast, activation of TLR5 and NOD2 increased basolateral potassium conductance, both in T84 cells (18.0 ± 4.1 and 18.4 ± 2.8, respectively) and in Caco-2 cells (21.2 ± 8.4 and 16.0 ± 3.6, respectively). TRAM-34 and AMP-PNP induced a decrease in basolateral potassium conductance upon TLR4 stimulation in both cell lines. Both KCa3.1- and Kir6-channels appear to be important mediators of this effect in IECs and could be potential targets for therapeutic agent development.NEW & NOTEWORTHY This study highlights that PRRs stimulation directly influences K+-channel conductance in IECs. TLR-2, -4, -7 stimulation decreased K+ conductance, whereas TLR5 and NOD2 stimulation had the opposite effect, leading to an increase of it instead. This study reports for the first time that KCa3.1- and Kir6-channels play a role in K+ transport pathways triggered by TLR4 stimulation. These findings suggest that KCa3.1- and Kir6-channels modulation may be a potential target for new therapeutic agents in IBD.


Assuntos
Doenças Inflamatórias Intestinais , Receptor 2 Toll-Like , Humanos , Receptor 2 Toll-Like/metabolismo , Células CACO-2 , Receptor 4 Toll-Like/metabolismo , Receptor 5 Toll-Like/metabolismo , Adenilil Imidodifosfato/metabolismo , Adenilil Imidodifosfato/farmacologia , Receptor 7 Toll-Like/metabolismo , Células Epiteliais/metabolismo , Canais de Potássio/metabolismo , Receptores Toll-Like/metabolismo , Receptores de Reconhecimento de Padrão/metabolismo , Potássio/metabolismo , Doenças Inflamatórias Intestinais/metabolismo , Eletrólitos/metabolismo , Eletrólitos/farmacologia , Proteína Adaptadora de Sinalização NOD2/metabolismo
2.
Lett Appl Microbiol ; 74(6): 924-931, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35239229

RESUMO

We studied the disinfection efficacy of boron-doped electrodes on Escherichia coli-contaminated water-based solutions in three different electrolytes, physiological solution (NaCl), phosphate buffer (PB), and phosphate buffer saline (PBS). The effect of the electrochemical oxidation treatment on the bacteria viability was studied by drop and spread plate cultivation methods, and supported by optical density measurements. We have found that bacterial suspensions in NaCl and PBS underwent a total inactivation of all viable bacteria within 10 min of the electrochemical treatment. By contrast, experiments performed in the PB showed a relatively minor decrease of viability by two orders of magnitude after 2 h of the treatment, which is almost comparable with the untreated control. The enhanced bacterial inactivation was assigned to reactive chlorine species, capable of penetrating the bacterial cytoplasmic membrane and killing bacteria from within.


Assuntos
Boro , Escherichia coli K12 , Boro/química , Boro/farmacologia , Eletrodos , Eletrólitos/farmacologia , Escherichia coli , Oxirredução , Fosfatos/farmacologia , Cloreto de Sódio/farmacologia
3.
Heart Surg Forum ; 24(5): E842-E848, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34623254

RESUMO

BACKGROUND: The aim of this study is to compare the efficacy of the microplegia solution and Del Nido cardioplegia solution in coronary artery bypass surgery with clinical, biochemical, and echocardiographic data. METHODS: Three hundred patients, who underwent coronary artery bypass surgery between January 2017 and January 2020, by the same surgical team were included in the study. Preoperative, operative and postoperative data (cardiac biomarker levels, cross-clamp and CPB times, echocardiographic measurements, etc.) of the patients were compared. RESULTS: In the study, cross-clamp time was significantly shorter in the DN cardioplegia group (55.60 ± 13.49 min/75.58 ± 12.43 min, P = 0.024). No significant difference was observed between the two groups in terms of intensive care stay, extubation time, hospital stay, and cardiopulmonary bypass time. In our study, it was shown that both the left and right ventricular ejection fraction was better protected in the Del Nido cardioplegia group (5.34±3.03 vs. 3.40±2.84, P = 0.017 and 3.82±1.19 vs. 2.28±1.87, P = 0.047, respectively), and the need for inotrope support was lower in this group (28% vs. 44%, P < 0.021). There was no significant difference between the groups, in terms of blood transfusion rates, IABP requirement. CONCLUSION: In light of short-term results, we can say that Del Nido cardioplegia provides better myocardial protection than microplegia. In addition, Del Nido cardioplegia can be given as a single dose for 90 minutes of cross-clamp time and therefore can be preferred to increase surgical comfort and reduce cross-clamp times.


Assuntos
Ponte de Artéria Coronária/métodos , Doença da Artéria Coronariana/cirurgia , Eletrólitos/farmacologia , Parada Cardíaca Induzida/métodos , Lidocaína/farmacologia , Sulfato de Magnésio/farmacologia , Manitol/farmacologia , Cloreto de Potássio/farmacologia , Bicarbonato de Sódio/farmacologia , Soluções/farmacologia , Volume Sistólico/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/fisiopatologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Retrospectivos , Resultado do Tratamento , Função Ventricular Direita/fisiologia , Adulto Jovem
4.
Heart Surg Forum ; 24(5): E808-E813, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34623240

RESUMO

OBJECTIVE: To investigate the effect of using del Nido cardioplegia+terminal hot-shot blood cardioplegia on myocardial protection and rhythm in isolated coronary bypass patients. MATERIAL AND METHODS: A total of 122 patients were given cold (+4-8C') del Nido cardioplegia antegrade and evaluated. Del Nido+terminal warm blood cardioplegia (TWBCP) was applied to 63 patients out of 122 patients, while del Nido cardioplegia alone was applied to the other 59 patients. The preoperative and postoperative data of the patients were recorded and compared. RESULTS: There was a significant statistical difference between the groups, in terms of volume with more cardioplegia in the del Nido+terminal warm blood cardioplegia group. Although there was no significant difference between cardiac arrest times in both groups, a statistically significant difference was found in the del Nido+terminal warm blood cardioplegia group in the starting to work time of the heart. No difference found between the groups regarding myocardial preservation. CONCLUSIONS: We can add a return to spontaneous sinus rhythm to the advantages of terminal warm blood cardioplegia and del Nido cardioplegia in literature. We think it would be a good strategy to extend the safe ischemic time limit of del Nido to 120 minutes with a terminal warm blood cardioplegia. It seems that cardioplegia techniques that will be developed by adding the successful and superior results of crystalloid cardioplegia applications, such as single dose del Nido in various open heart surgery operations and the superior myocardial return effects of terminal warm blood cardioplegia, will be used routinely in the future.


Assuntos
Ponte de Artéria Coronária/métodos , Doença da Artéria Coronariana/cirurgia , Eletrólitos/farmacologia , Parada Cardíaca Induzida/métodos , Frequência Cardíaca/efeitos dos fármacos , Lidocaína/farmacologia , Sulfato de Magnésio/farmacologia , Manitol/farmacologia , Complicações Pós-Operatórias/prevenção & controle , Cloreto de Potássio/farmacologia , Bicarbonato de Sódio/farmacologia , Soluções/farmacologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Soluções Cardioplégicas/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
5.
Transfusion ; 60(12): 2991-3000, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33032376

RESUMO

BACKGROUND: Literature is beginning to challenge the belief that it is unsafe to coinfuse red blood cells (RBCs) with solutions other than isotonic saline. We recently showed that additive-free RBCs tolerated coincubation with Plasma-Lyte or catecholamines dissolved in normal saline (NS), though 5% dextrose in water (D5W) promoted hemolysis. Herein, we evaluate the effect of coincubating crystalloids on additive-preserved RBC hemolysis, aggregation, and membrane deformability. STUDY DESIGN AND METHODS: RBCs were coincubated 5 minutes with plasma, NS, Plasma-Lyte, lactated Ringer's (LR) or D5W (1 mL PRBC +131.3 µL solution). Samples were then assessed for hemolysis (free hemoglobin), aggregation (critical shear stress [mPa]), and membrane deformability (elongation index [EI]). Significance (P ≤ .05) by t test or ANOVA with post-hoc Tukey-Kramer test. RESULTS: Additive-prepared RBCs coincubated with crystalloid instead of plasma demonstrated: (a) no increase in hemolysis as indicated by plasma free hemoglobin levels that is likely to be clinically relevant; (b) no increase, but in some cases a decrease, in aggregation as indicated by critical shear stress; and (c) in some combinations, a deterioration in deformability. When present, the deformability decrease was likely clinically insignificant in degree, and always returned to normal when the crystalloid was subsequently diluted out with plasma. CONCLUSION: Our data suggest that additive-prepared RBCs coincubated for 5 minutes with any of four common crystalloids demonstrate no clinically relevant increased lysis, increased aggregation, or decreased deformability.


Assuntos
Soluções Cristaloides/farmacologia , Eletrólitos/farmacologia , Agregação Eritrocítica/efeitos dos fármacos , Deformação Eritrocítica/efeitos dos fármacos , Eritrócitos/metabolismo , Soluções Cristaloides/química , Hemólise , Humanos
6.
Neuropediatrics ; 51(6): 397-400, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32842160

RESUMO

PURPOSE: Ketogenic diets (KDs) are used to treat epilepsies resistant to pharmacotherapy or some inborn errors of metabolism. For prolonged anesthesia, use of balanced electrolyte solutions (BESs) supplemented with 0.5% glucose has been advocated to maintain ketosis while preventing hypoglycemia. Unfortunately, there is no BES containing 0.5% glucose available from pharmacies. In a laboratory study, we investigated the physical and chemical stability of different BES mixtures containing 0.5% glucose. METHODS: In total, six approaches were chosen to create a BES with 0.5% glucose: three different glucose-free BESs were supplemented with glucose. Additionally, commercially available BES containing 1% glucose was diluted with three different glucose-free BESs to obtain a solution containing 0.5% glucose. Turbidity, pH, electrical conductivity, and macroscopic appearance of these solutions were measured immediately, at 24 hours, and after 7 days, and were compared with the original BES. RESULTS: Turbidity, pH, and electrical conductivity, as well as macroscopic appearance did not exceed the changes of the controls. CONCLUSIONS: No signs of incompatibility reactions could be observed in a 1-week time period. Our study supports the stability of the examined BES containing 0.5% glucose for prolonged anesthesia in patients on KD. Clinical studies are needed to evaluate if BES containing 0.5% glucose is superior in patients on KDs.


Assuntos
Dieta Cetogênica , Eletrólitos/farmacologia , Glucose/farmacologia , Humanos , Soluções/farmacologia
7.
Phys Chem Chem Phys ; 22(12): 6749-6754, 2020 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-32167106

RESUMO

The enzymatic activity of alcohol dehydrogenase (ADH) in the presence of a range of electrolytes is investigated. In the presence of 150 and 200 mM cations a substantial increase in activity following the series GnCl < CsCl < KCl ∼ NaCl < LiCl was observed with a 69% increase in the presence of KCl 200 mM with respect to the salt-free solution. In the presence of 150 and 200 mM anions the increase in activity followed an ion specific trend NaF ∼ NaCl ∼ NaBr > no salt > NaClO4 > NaSCN with a peak in activity increase of 75% in the presence of NaBr. The values of the Michaelis-Menten constant (Km) did not show any significant ion specific effect, while the maximum rate (Vmax) of ethanol oxidation to acetaldehyde was strongly ion specific. The changes in specific activity and Vmax in the presence of anions likely arises from ion specific interactions with charged residues in the active site of ADH. The data indicate that the enzymatic activity of alcohol dehydrogenase can be modulated by the nature of electrolytes at physiological concentration.


Assuntos
Álcool Desidrogenase/metabolismo , Eletrólitos/química , Saccharomyces cerevisiae/enzimologia , Álcool Desidrogenase/química , Eletrólitos/farmacologia , Ativação Enzimática/efeitos dos fármacos , Etanol/metabolismo , Oxirredução
8.
Heart Surg Forum ; 23(5): E689-E695, 2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-32990578

RESUMO

BACKGROUND: St. Thomas (ST) and Del Nido (DN) cardioplegic solutions are widely used for myocardial protection during cardiac surgery. In 2016, our university hospital shifted from modified St. Thomas to Del Nido solution for both adult and pediatric cardiac surgery. This retrospective study was conducted to compare ST and DN solutions regarding surgical workflow and clinical outcome in pediatric and adult patients undergoing cardiac surgery. METHODS: We reviewed 220 patients who underwent cardiac surgery requiring cardioplegic arrest. Patients were categorized in 2 groups: ST (n = 110) and DN (n = 110). Each group included 60 pediatric and 50 adult patients. Demographic, intraoperative, and postoperative variables were collected. RESULTS: In pediatric patients, no significant difference was found between the 2 groups regarding clamping time, bypass time, need for defibrillation, inotropic score, postoperative ejection fraction (EF), period of mechanical ventilation, intensive care unit stay, or postoperative arrhythmias. One patient in the ST group required mechanical support by extracorporeal membrane oxygenation. We had 5 cases of pediatric mortality (3 in DN and 2 in ST, P = .64). In adult patients, significantly fewer patients in the DN group needed defibrillation than in the ST group. No significant difference was found regarding clamping time, inotropic score, or intraaortic balloon pump use. Mortality in adult patients was 6 cases (4 in ST group and 2 in DN group). CONCLUSION: DN cardioplegia solution is as safe as ST solution in pediatric and adult cardiac surgery. It has comparable results of myocardial protection and clinical outcome, with superiority regarding uninterrupted surgery and lower rate of defibrillation.


Assuntos
Procedimentos Cirúrgicos Cardíacos/métodos , Eletrólitos/farmacologia , Parada Cardíaca Induzida/métodos , Lidocaína/farmacologia , Sulfato de Magnésio/farmacologia , Manitol/farmacologia , Cloreto de Potássio/farmacologia , Bicarbonato de Sódio/farmacologia , Soluções/farmacologia , Adolescente , Adulto , Bicarbonatos/farmacologia , Cloreto de Cálcio/farmacologia , Soluções Cardioplégicas/farmacologia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Magnésio/farmacologia , Masculino , Período Pós-Operatório , Estudos Retrospectivos , Cloreto de Sódio/farmacologia , Adulto Jovem
9.
Int J Mol Sci ; 21(19)2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33023274

RESUMO

Zinc-air batteries (ZABs) offer high specific energy and low-cost production. However, rechargeable ZABs suffer from a limited cycle life. This paper reports that potassium persulfate (KPS) additive in an alkaline electrolyte can effectively enhance the performance and electrochemical characteristics of rechargeable zinc-air flow batteries (ZAFBs). Introducing redox additives into electrolytes is an effective approach to promote battery performance. With the addition of 450 ppm KPS, remarkable improvement in anodic currents corresponding to zinc (Zn) dissolution and limited passivation of the Zn surface is observed, thus indicating its strong effect on the redox reaction of Zn. Besides, the addition of 450 ppm KPS reduces the corrosion rate of Zn, enhances surface reactions and decreases the solution resistance. However, excess KPS (900 and 1350 ppm) has a negative effect on rechargeable ZAFBs, which leads to a shorter cycle life and poor cyclability. The rechargeable ZAFB, using 450 ppm KPS, exhibits a highly stable charge/discharge voltage for 800 cycles. Overall, KPS demonstrates great promise for the enhancement of the charge/discharge performance of rechargeable ZABs.


Assuntos
Fontes de Energia Elétrica , Eletrólitos/química , Compostos de Potássio/química , Sulfatos/química , Zinco/química , Ar , Eletrólitos/farmacologia , Compostos de Potássio/farmacologia , Sulfatos/farmacologia
10.
Biochemistry ; 58(6): 590-607, 2019 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-30489059

RESUMO

Intraneuronal aggregation of TDP-43 is seen in 97% of all amyotrophic lateral sclerosis cases and occurs by a poorly understood mechanism. We developed a simple in vitro model system for the study of full-length TDP-43 aggregation in solution and in protein droplets. We found that soluble, YFP-tagged full-length TDP-43 (yTDP-43) dimers can be produced by refolding in low-salt HEPES buffer; these solutions are stable for several weeks. We found that physiological electrolytes induced reversible aggregation of yTDP-43 into 10-50 nm tufted particles, without amyloid characteristics. The order of aggregation induction potency was K+ < Na+ < Mg2+ < Ca2+, which is the reverse of the Hofmeister series. The kinetics of aggregation were fit to a single-step model, and the apparent rate of aggregation was affected by yTDP-43 and NaCl concentrations. While yTDP-43 alone did not form stable liquid droplets, it partitioned into preformed Ddx4N1 droplets, showing dynamic diffusion behavior consistent with liquid-liquid phase transition, but then aggregated over time. Aggregation of yTDP-43 in droplets also occurred rapidly in response to changes in electrolyte concentrations, mirroring solution behavior. This was accompanied by changes to droplet localization and solvent exchange. Exposure to extracellular-like electrolyte conditions caused rapid aggregation at the droplet periphery. The aggregation behavior of yTDP-43 is controlled by ion-specific effects that occur at physiological concentrations, suggesting a mechanistic role for local electrolyte concentrations in TDP-43 proteinopathies.


Assuntos
Amiloide/química , Proteínas de Ligação a DNA/química , Eletrólitos/farmacologia , Gotículas Lipídicas/efeitos dos fármacos , Agregados Proteicos/efeitos dos fármacos , Amiloide/efeitos dos fármacos , Proteínas de Bactérias/metabolismo , Proteínas de Ligação a DNA/efeitos dos fármacos , Proteínas de Ligação a DNA/metabolismo , Humanos , Proteínas Luminescentes/metabolismo
11.
Anal Chem ; 90(12): 7422-7427, 2018 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-29786428

RESUMO

Layer-by-layer dissolution and permeable pore formation are two typical membrane damage pathways, which induce membrane function disorder and result in serious disease, such as Alzheimer's disease, Keshan disease, Sickle-cell disease, and so on. To effectively distinguish and sensitively monitor these two typical membrane damage pathways, a facile electrochemical impedance strategy was developed on a porous self-assembly monolayer (pSAM) supported bilayer lipid membrane (BLM). The pSAM was prepared by selectively electrochemical reductive desorption of the mercaptopropionic acid in a mixed mercaptopropionic acid/11-mercaptoundecanoic acid self-assembled monolayer, which created plenty of nanopores with tens of nanometers in diameter and several nanometers in height (defined as inner-pores). The ultralow aspect ratio of the inner-pores was advantageous to the mass transfer of electrochemical probe [Fe(CN)6]3-/4-, simplifying the equivalent electric circuit for electrochemical impedance spectroscopy analysis at the electrode/membrane interface. [Fe(CN)6]3-/4- transferring from the bulk solution into the inner-pore induce significant changes of the interfacial impedance properties, improving the detection sensitivity. Based on these, the different membrane damage pathways were effectively distinguished and sensitively monitored with the normalized resistance-capacitance changes of inner-pore-related parameters including the electrolyte resistance within the pore length ( Rpore) and the metal/inner-pore interfacial capacitance ( Cpore) and the charge-transfer resistance ( Rct-in) at the metal/inner-pore interface.


Assuntos
Espectroscopia Dielétrica/métodos , Membranas/patologia , Capacitância Elétrica , Eletrólitos/farmacologia , Ácidos Graxos , Bicamadas Lipídicas , Lipídeos de Membrana , Nanoporos , Compostos de Sulfidrila
12.
Artif Organs ; 41(11): E240-E250, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28800676

RESUMO

Static cold storage is accompanied with a partial safe ischemic interval for donor hearts. In this current study, a machine perfusion system was built to provide a better preservation for the donor heart and assessment for myocardial function. Chinese mini-swine (weight 30-35 kg, n = 16) were randomly divided into HTK, Celsior, and Heartbeat groups. All donor hearts were respectively preserved for 8 hours under static cold storage or machine perfusion. The perfusion solution is aimed to maintain its homeostasis based on monitoring the Heartbeat group. The ultrastructure of myocardium suggests better myocardial protection in the Heartbeat group compared with HTK or Celsior-preserved hearts. The myocardial and coronary artery structural and functional integrity was evaluated by immunofluorescence and Western blots in the Heartbeat. In the Heartbeat group, donor hearts maintained a high adenosine triphosphate level. Bcl-2 and Beclin-1 protein demonstrates high expression in the Celsior group. The Heartbeat system can be used to preserve donor hearts, and it could guarantee the myocardial and endothelial function of hearts during machine perfusion. Translating Heartbeat into clinical practice, it is such as to impact on donor heart preservation for cardiac transplantation.


Assuntos
Oxigenação por Membrana Extracorpórea/instrumentação , Coração , Hemofiltração/instrumentação , Preservação de Órgãos/instrumentação , Perfusão/instrumentação , Animais , Isquemia Fria , Temperatura Baixa , Vasos Coronários/efeitos dos fármacos , Vasos Coronários/ultraestrutura , Citoproteção , Dissacarídeos/farmacologia , Eletrólitos/farmacologia , Metabolismo Energético , Desenho de Equipamento , Oxigenação por Membrana Extracorpórea/efeitos adversos , Oxigenação por Membrana Extracorpórea/métodos , Glucose/farmacologia , Glutamatos/farmacologia , Glutationa/farmacologia , Coração/efeitos dos fármacos , Coração/fisiopatologia , Hemofiltração/efeitos adversos , Hemofiltração/métodos , Histidina/farmacologia , Manitol/farmacologia , Modelos Animais , Contração Miocárdica , Miocárdio/metabolismo , Miocárdio/ultraestrutura , Preservação de Órgãos/efeitos adversos , Preservação de Órgãos/métodos , Soluções para Preservação de Órgãos/farmacologia , Perfusão/efeitos adversos , Perfusão/métodos , Cloreto de Potássio/farmacologia , Procaína/farmacologia , Suínos , Porco Miniatura , Fatores de Tempo
13.
Bull Exp Biol Med ; 163(1): 42-45, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28580525

RESUMO

Relationship between changes in the erythrocyte sedimentation rate in rats and concentration and charge of polyelectrolyte microcapsules was studied by the Panchenkov method. Positively charged microcapsules reduced erythrocyte sedimentation rate in a concentrationdependent manner. This effect was related to a decrease in the content of high-molecularweight proteins in the plasma due to their adsorption in positively charged microcapsules with polyacrylamide surface layer.


Assuntos
Sedimentação Sanguínea/efeitos dos fármacos , Cápsulas/química , Polieletrólitos/química , Polieletrólitos/farmacologia , Animais , Eletrólitos/química , Eletrólitos/farmacologia , Ratos , Ratos Wistar
14.
Angew Chem Int Ed Engl ; 56(18): 5031-5034, 2017 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-28370842

RESUMO

A membrane-intercalating conjugated oligoelectrolyte (COE), PTTP, was designed and synthesized with the goal of providing red-shifted absorption spectra relative to previously synthesized COE analogs. Specifically, electron-rich and electron-poor subunits were introduced in the conjugated backbone to modulate the band gap. PTTP exhibits maxima of absorption at 507 nm and of emission at 725 nm. PTTP can also efficiently function to generate singlet oxygen in situ (ΦΔ ≈20 %) and has appropriate topology and dimensions to interact with lipid membranes. The resulting rapid membrane insertion and sensitizing ability provide PTTP with a highly efficient antibacterial capability under a low light dose (0.6 J cm-2 ) toward Gram-negative bacteria E. coli, making it a remarkably efficient optically mediated antimicrobial agent.


Assuntos
Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Escherichia coli/efeitos dos fármacos , Bicamadas Lipídicas/metabolismo , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Eletrólitos/química , Eletrólitos/farmacologia , Infecções por Escherichia coli/tratamento farmacológico , Humanos , Fotoquimioterapia , Oxigênio Singlete/metabolismo
15.
J Transl Med ; 14: 40, 2016 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-26847569

RESUMO

BACKGROUND: In kidney transplantation, the conditions of organ preservation following removal influence function recovery. Current static preservation procedures are generally based on immersion in a cold-storage solution used under atmospheric air (approximately 78 kPa N2, 21 kPa O2, 1 kPa Ar). Research on static cold-preservation solutions has stalled, and modifying the gas composition of the storage medium for improving preservation was considered. Organoprotective strategies successfully used noble gases and we addressed here the effects of argon and xenon on graft preservation in an established preclinical pig model of autotransplantation. METHODS: The preservation solution Celsior saturated with pure argon (Argon-Celsior) or xenon (Xenon-Celsior) at atmospheric pressure was tested versus Celsior saturated with atmospheric air (Air-Celsior). The left kidney was removed, and Air-Celsior (n = 8 pigs), Argon-Celsior (n = 8) or Xenon-Celsior (n = 6) was used at 4 °C to flush and store the transplant for 30 h, a duration that induced ischemic injury in our model when Air-Celsior was used. Heterotopic autotransplantation and contralateral nephrectomy were performed. Animals were followed for 21 days. RESULTS: The use of Argon-Celsior vs. Air-Celsior: (1) improved function recovery as monitored via creatinine clearance, the fraction of excreted sodium and tubulopathy duration; (2) enabled diuresis recovery 2-3 days earlier; (3) improved survival (7/8 vs. 3/8 pigs survived at postoperative day-21); (4) decreased tubular necrosis, interstitial fibrosis, apoptosis and inflammation, and preserved tissue structures as observed after the natural death/euthanasia; (5) stimulated plasma antioxidant defences during the days following transplantation as shown by monitoring the "reduced ascorbic acid/thiobarbituric acid reactive substances" ratio and Hsp27 expression; (6) limited the inflammatory response as shown by expression of TNF-alpha, IL1-beta and IL6 as observed after the natural death/euthanasia. Conversely, Xenon-Celsior was detrimental, no animal surviving by day-8 in a context where functional recovery, renal tissue properties and the antioxidant and inflammation responses were significantly altered. Thus, the positive effects of argon were not attributable to the noble gases as a group. CONCLUSIONS: The saturation of Celsior with argon improved early functional recovery, graft quality and survival. Manipulating the gas composition of a preservation medium constitutes therefore a promising approach to improve preservation.


Assuntos
Argônio/farmacologia , Transplante de Rim , Preservação de Órgãos , Ar , Animais , Antioxidantes/farmacologia , Dissacarídeos/farmacologia , Eletrólitos/farmacologia , Células Epiteliais/efeitos dos fármacos , Feminino , Glutamatos/farmacologia , Glutationa/farmacologia , Sobrevivência de Enxerto/efeitos dos fármacos , Histidina/farmacologia , Inflamação/patologia , Manitol/farmacologia , Modelos Animais , Reperfusão , Sus scrofa , Transplante Heterotópico , Xenônio
16.
Transfusion ; 56(7): 1786-91, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27145397

RESUMO

BACKGROUND: Preparation of umbilical cord blood units (CBUs) for infusion requires a step of dilution or washing to reduce the toxicity of the dimethyl sulfoxide present in the freezing solution. However, the worldwide shortage of clinical-grade dextran 40, the most widely used cord blood dilution or washing solution, prompted us to search for an alternative solution. We elected to evaluate the performance of alternative solutions that could be used as potential replacements for the dextran 40-based solution. STUDY DESIGN AND METHODS: Frozen CBUs were rapidly thawed and immediately diluted 1:4 in each of 10 dilution solution variants of dextran 40, Plasma-lyte, or Hespan. We compared these alternatives by assessing viability, CD34, CD45, and colony-forming units recovery postthaw. RESULTS: A significantly lower CD34 and CD45 recovery was observed in all solutions without human serum albumin (HSA). All solutions with 5% HSA gave recovery, viability, and potency figures similar to the dextran 40/HSA solution. CONCLUSION: Based on our results and considering that Plasma-lyte A (PA)/HSA is already used for the thawing of CD34 from mobilized blood, we conclude that PA/HSA could be a safe and efficient solution for the replacement of dextran 40-based dilution solutions.


Assuntos
Criopreservação , Dextranos/farmacologia , Sangue Fetal/efeitos dos fármacos , Substitutos do Plasma/farmacologia , Antígenos CD34/análise , Sobrevivência Celular , Dimetil Sulfóxido/isolamento & purificação , Eletrólitos/farmacologia , Humanos , Derivados de Hidroxietil Amido/farmacologia , Antígenos Comuns de Leucócito/análise , Células-Tronco
17.
Vasc Med ; 21(5): 413-421, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27216870

RESUMO

Traditional methods of intraoperative human saphenous vein preparation for use as bypass grafts can be deleterious to the conduit. The purpose of this study was to characterize acute graft preparation injury, and to mitigate this harm via an improved preparation technique. Porcine saphenous veins were surgically harvested (unprepared controls, UnP) and prepared using traditional (TraP) and improved preparations (ImP). The TraP used unregulated radial distension, marking with a surgical skin marker and preservation in heparinized normal saline. ImP used pressure-regulated distension, brilliant blue FCF-based pen marking and preservation in heparinized Plasma-Lyte A. Rings from each preparation were suspended in a muscle bath for characterization of physiologic responses to vasoactive agents and viscoelasticity. Cellular viability was assessed using the methyl thiazolyl tetrazolium (MTT) assay and the terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay for apoptosis. Contractile responses to potassium chloride (110 mM) and phenylephrine (10 µM), and endothelial-dependent and independent vasodilatory responses to carbachol (0.5 µM) and sodium nitroprusside (1 µM), respectively, were decreased in TraP tissues compared to both UnP and ImP tissues (p ⩽ 0.05). TraP tissues demonstrated diminished viscoelasticity relative to UnP and ImP tissues (p ⩽ 0.05), and reduced cellular viability relative to UnP control (p ⩽ 0.01) by the MTT assay. On the TUNEL assay, TraP tissues demonstrated a greater degree of apoptosis relative to UnP and ImP tissues (p ⩽ 0.01). In conclusion, an improved preparation technique prevents vascular graft smooth muscle and endothelial injury observed in tissues prepared using a traditional approach.


Assuntos
Preservação de Órgãos/métodos , Veia Safena/transplante , Coleta de Tecidos e Órgãos/métodos , Vasoconstrição , Vasodilatação , Animais , Anticoagulantes/farmacologia , Apoptose , Sobrevivência Celular , Elasticidade , Eletrólitos/farmacologia , Heparina/farmacologia , Modelos Animais , Preservação de Órgãos/efeitos adversos , Soluções para Preservação de Órgãos/farmacologia , Veia Safena/efeitos dos fármacos , Veia Safena/patologia , Veia Safena/fisiopatologia , Cloreto de Sódio/farmacologia , Sus scrofa , Fatores de Tempo , Coleta de Tecidos e Órgãos/efeitos adversos , Rigidez Vascular , Vasoconstrição/efeitos dos fármacos , Vasoconstritores/farmacologia , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologia , Viscosidade
18.
Artif Organs ; 40(5): 489-96, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26526678

RESUMO

Organ preservation solution has been designed to attenuate the detrimental effects during the ischemic period. The aim of this study was to systematically evaluate the evidence comparing preservation solutions for heart preservation. Studies were searched in PubMed, Embase, the Cochrane Library, the Transplant Library, and the International Clinical Trials Registry Platform. The primary outcomes were patient survival and donor heart dysfunction. The secondary outcomes were in-hospital mortality and enzyme gene expression. The University of Wisconsin solution (UW) was associated with a significantly improved survival at 30 days and 90 days (hazard ratio = 1.16, 95% confidence interval [CI] = 1.11-1.22, P < 0.00001; risk difference [RD] = 0.03, 95% CI = 0.01-0.05, P = 0.002), compared with Celsior. Hearts preserved with UW exhibited less ischemic necrosis than those preserved with Celsior (RD = -0.07, 95% CI = -0.08 to 0.05, P < 0.00001). UW was associated with better survival compared with histidine-tryptophan-ketoglutarate solution (HTK). There was no statistical difference in donor heart dysfunction and in-hospital mortality outcomes when comparing HTK with Celsior solution. During static cold storage preservation, this study suggests that UW solution has better clinical outcomes for heart transplantation compared with the other two organ preservation solutions. Besides, the protective effect of Celsior solution is similar to HTK solution in donor heart preservation.


Assuntos
Coração/efeitos dos fármacos , Soluções para Preservação de Órgãos/farmacologia , Preservação de Órgãos/métodos , Adenosina/farmacologia , Aloenxertos , Alopurinol/farmacologia , Dissacarídeos/farmacologia , Eletrólitos/farmacologia , Glucose/farmacologia , Glutamatos/farmacologia , Glutationa/farmacologia , Coração/fisiologia , Coração/fisiopatologia , Transplante de Coração/métodos , Histidina/farmacologia , Humanos , Insulina/farmacologia , Manitol/farmacologia , Cloreto de Potássio/farmacologia , Procaína/farmacologia , Rafinose/farmacologia
19.
Blood Purif ; 42(1): 18-26, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26949936

RESUMO

AIMS: To evaluate the capability of an electrolytes-enriched solution to prevent metabolic disorders during continuous veno-venous hemodiafiltration (CVVHDF). METHODS: Serum biochemistry and clinical tolerance were compared during CVVHDF treatments with an electrolyte-enriched (Phoxilium) or standard solutions in 10 acute renal failure patients. RESULTS: As compared to standard fluids, serum potassium and phosphate levels were maintained in the normal range with Phoxilium without any supplementation but total serum calcium levels were significantly lower. Bicarbonatemia was slightly higher (24-26 vs. 21.5-24.5 mmol/l, p < 0.05) with conventional solutions and was associated with a significant increased level of pH (>7.44). Despite the absence of glucose in the Phoxilium solution, blood glucose levels and glucose supplementation were similar between treatments. Clinical tolerance and efficiency of CVVHDF sessions were comparable. CONCLUSION: Phoxilium effectively prevented hypophosphatemia and hypokalemia during CVVHDF. It was, however, associated with a slight metabolic acidosis and hypocalcemia compared with conventional solutions.


Assuntos
Injúria Renal Aguda/terapia , Hemodiafiltração/métodos , Soluções para Hemodiálise/uso terapêutico , Doenças Metabólicas/prevenção & controle , Terapia de Substituição Renal/métodos , Injúria Renal Aguda/complicações , Idoso , Estudos Cross-Over , Eletrólitos/farmacologia , Eletrólitos/uso terapêutico , Hemodiafiltração/efeitos adversos , Soluções para Hemodiálise/química , Soluções para Hemodiálise/farmacologia , Humanos , Hipopotassemia/prevenção & controle , Hipofosfatemia/prevenção & controle , Doenças Metabólicas/etiologia , Pessoa de Meia-Idade , Terapia de Substituição Renal/efeitos adversos
20.
Paediatr Anaesth ; 26(6): 590-8, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27012479

RESUMO

BACKGROUND: Acetate-containing balanced electrolyte solutions are frequently used for fluid therapy in pediatric anesthesia, but no studies investigating the compatibility with common anesthetic drugs are available. AIM: To reveal possible incompatibilities between common anesthetic drugs and the acetate-containing balanced electrolyte solutions BS (Sterofundin ISO; B.Braun Melsungen AG, Melsungen, Germany) and BS-G1 (E148G1 Päd; Serumwerk Bernburg AG, Bernburg, Germany), with normal saline (NS) as control. METHODS: All tested infusion solutions were mixed 1 : 1 with 28 common anesthetic drugs in concentrations used in daily clinical practice. Electrical conductivity, pH, and turbidimetric light diffusion at 405 nm were measured. Macroscopic changes such as gross precipitation, change in color, or bubble formation were also assessed. All measurements were performed immediately after mixing as well as 30 and 60 min after. RESULTS: The vast majority of drugs showed no significant change in pH, electric conductivity, turbidimetric detectable light diffusion, or macroscopic appearance after mixing with BS, BS-G1, and NS. Phenytoin immediately precipitated in response to all tested solutions as did diazepam. Thiopental precipitated after mixing with BS only. CONCLUSIONS: Most of the tested drugs did not show any signs or evidence of incompatibility reactions. However, phenytoin and diazepam should not be in contact with the three tested solutions, including NS. Thiopental should be used with caution because it can precipitate in solutions with a low pH (e.g., BS).


Assuntos
Acetatos/farmacologia , Anestésicos/farmacologia , Incompatibilidade de Medicamentos , Eletrólitos/farmacologia , Anestesia , Criança , Interações Medicamentosas , Hidratação/métodos , Humanos , Equilíbrio Hidroeletrolítico
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