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Dronedarone (DRN) is a clinically used drug to mitigate arrhythmias with multichannel block properties, including the sodium channel Na v 1.5. Extracellular acidification is known to change the pharmacological properties of several antiarrhythmic drugs. Here, we explore how modification in extracellular pH (pHe) shapes the pharmacological profile of DRN upon Na v 1.5 sodium current (I Na ) and in the ex vivo heart preparation. Embryonic human kidney cells (HEK293T/17) were used to transiently express the human isoform of Na v 1.5 α-subunit. Patch-Clamp technique was employed to study I Na . Neurotoxin-II (ATX-II) was used to induce the late sodium current (I NaLate ). Additionally, ex vivo Wistar male rat preparations in the Langendorff system were utilized to study electrocardiogram (ECG) waves. DRN preferentially binds to the closed state inactivation mode of Na v 1.5 at pHe 7.0. The recovery from I Na inactivation was delayed in the presence of DRN in both pHe 7.0 and 7.4, and the use-dependent properties were distinct at pHe 7.0 and 7.4. However, the potency of DRN upon the peak I Na , the voltage dependence for activation, and the steady-state inactivation curves were not altered in both pHe tested. Also, the pHe did not change the ability of DRN to block I NaLate . Lastly, DRN in a concentration and pH dependent manner modulated the QRS complex, QT and RR interval in clinically relevant concentration. Thus, the pharmacological properties of DRN upon Na v 1.5 and ex vivo heart preparation partially depend on the pHe. The pHe changed the biological effect of DRN in the heart electrical function in relevant clinical concentration., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests, conflict of interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The adsorption of surfactants on rock surfaces can modify their hydrophobicity, surface charge, and other important properties that govern advanced oil recovery processes, such as decreasing the interfacial tension between water and oil and increasing permeability. Generally, the need to control and/or reduce surfactant adsorption on reservoir rock surfaces has been a challenging task in enhanced oil recovery (EOR) methods, as it directly impacts the project's economics. This requires a comprehensive study and understanding of the adsorption mechanism on rocks. This work investigates the adsorption process of nonionic surfactants from the family of ethoxylated nonylphenols in alcoholic micellar solutions on sandstone rock surfaces. The systems used in the experiments consisted of NP 9.5EO, NP 11EO, and NP 15EO, butanol as an amphiphilic solvent, and a saline solution (2% KCl) as the aqueous phase. The experiments were conducted according to the Scheffé network and showed an adsorption efficiency of 66.89% for NP-15EO, 67.15% for NP-11EO, and 70.60% for NP-9.5EO, thus proving that the higher the degree of ethoxylation of nonylphenols, the lower the adsorption capacity. Point F was chosen as the optimum point since this point remained constant during the experiments, besides being a water-rich region with low butanol content. The sandstone exhibited oil-favorable wettability, which after treatment resulted in wettability inversion, with a decrease in the contact angle with water, a factor that can increase oil recovery. Adsorption isotherm modeling was also performed to investigate the adsorption mechanism. All adsorption tests followed and best fit the Redlich-Peterson isotherm, showing that the adsorption process occurs in monolayers and multilayers. The experimental methodology also involves analyses of mineralogy, morphology, thermal stability, and surface charge of the sandstone rock.

Purpose: To describe a novel bailout technique to approach below-the-ankle (BTA) chronic total occlusions or plantar-arch severe disease where the balloon/catheter is unable to follow the crossing guidewire and no other described recanalization approach is feasible., Technique: When facing a complex BTA revascularization, if the guidewire crosses but the balloon cannot progress due to a lack of pushability, an antegrade puncture of the infrapopliteal vessel where the tip of the guidewire lays is performed. The guidewire is then carefully navigated through this distal BTA vessel into the needle to achieve its rendezvous and externalization. A low-profile balloon is inserted through the femoral access and advanced till the non-crossable point of the BTA vessels. A torque device is then attached to the proximal hub of the balloon, and the through-and-through guidewire is subsequently pulled from the new distal access, allowing the balloon to be dragged across the lesion together with the wire., Conclusion: The below-the-ankle antegrade teleferic (BAT) technique may be considered for highly complex BTA revascularization procedures where the wire crosses the lesion, but no other device can be tracked over it., Clinical Impact: The clinical impact of this article lies in the description of a bailout technique for BTA revascularization where the guidewire crosses, but no device can be advanced. This technique can be helpful in scenarios where failure to achieve success could result in limb loss. The BAT technique provides a solution in extremely challenging cases, enhancing technical success, improving outcomes and potentially preserving the limbs of patients who would otherwise face amputation, if not revascularized.The video shows the BAT technique performed with a support catheter under fluoroscopy: antegrate puncture of the DP, advancement of the support catheter over the wire, rendezvous of the guidewire in the catheter and subsequent externalization of the wire., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: The purpose of the study is to describe a bailout technical strategy to prevent below-the-knee (BTK) distal embolization during procedures with increased inherent risk using universally-available "off-the-shelf" devices., Technique: A conventional retrograde access is obtained of the BTK target vessel where embolization protection is sought. Before starting any potential proximal maneuver with an associated significant risk of distal embolization (eg, atherectomy and mechanical thrombectomy), a low-profile balloon is inserted and inflated through the distal retrograde access, so that any debris resulting from the recanalization procedure is blocked by the stagnant column of blood generated by the inflated balloon. Once the revascularization procedure has been completed, a 4F curved catheter is antegradely advanced down to the distally-inflated balloon, and in case of distal embolization the debris is aspirated in a standard fashion way., Conclusion: A retrograde balloon-assisted "off-the-shelf" embolic protection approach may be considered for BTK revascularization procedures where there is an inherent increased risk of distal trash, especially in the presence of distal single-vessel runoff., Clinical Impact: Distal embolization following endovascular procedures can have devastating consequences and there is a general recommendation for selective use of EPDs in high-risk-scenarios. The increased cost and low availability of the current EPD devices for BTK/BTA arteries have prohibited their widespread use. The retrograde balloon-assisted "off-the-shelf" EPD prevents distal embolization during procedures with increased risk of distal trash using inexpensive, nonspecific equipment available in any basic endovascular suite., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The standard method used to quantify free acidity (FA) in vegetable oil is neutralization titration, which requires many toxic chemicals and depends on an analyst's experience in detecting endpoints. Here, a digital image colorimetry (DIC) method using a smartphone camera was developed to measure FA in vegetable oils. A cupric acetate solution was used to produce the colorimetric reaction. The coloured solutions were imaged, and R values (from the RGB colour system) were calibrated against the respective FAs in the standards. The FA values of the samples were determined by standard addition calibration. These results were compared to measurements of FA obtained by the standard titrimetric method. An excellent correlation was obtained, with an R 2 of 0.98 and a mean absolute error of 0.06%. The chemicals needed for analysis were reduced by approximately 90%. Thus, DIC is a less subjective and more economical method for determining FA in vegetable oils., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Amiodarone (AMIO) is an antiarrhythmic drug with the pKa in the physiological range. Here, we explored how mild extracellular pH (pHe) changes shape the interaction of AMIO with atrial tissue and impact its pharmacological properties in the classical model of sea anemone sodium channel neurotoxin type 2 (ATX) induced late sodium current (I Na-Late ) and arrhythmias., Method: Isolated atrial cardiomyocytes from male Wistar rats and human embryonic kidney cells expressing SCN5A Na + channels were used for patch-clamp experiments. Isolated right atria (RA) and left atria (LA) tissue were used for bath organ experiments., Results: A more acidophilic pHe caused negative inotropic effects on isolated RA and LA atrial tissue, without modification of the pharmacological properties of AMIO. A pHe of 7.0 changed the sodium current (I Na ) related components of the action potential (AP), which was enhanced in the presence of AMIO. ATXinduced arrhythmias in isolated RA and LA. Also, ATX prolonged the AP duration and enhanced repolarization dispersion in isolated cardiomyocytes in both pHe 7.4 and pHe 7.0. Pre-incubation of the isolated RA and LA and isolated atrial cardiomyocytes with AMIO prevented arrhythmias induced by ATX only at a pHe of 7.0. Moreover, AMIO was able to block I Na-Late induced by ATX only at a pHe of 7.0., Conclusion: The pharmacological properties of AMIO concerning healthy rat atrial tissue are not dependent on pHe. However, the prevention of arrhythmias induced by I Na-Late is pHe-dependent. The development of drugs analogous to AMIO with charge stabilization may help to create more effective drugs to treat arrhythmias related to the I Na-Late ., (© 2024. The Author(s) under exclusive licence to Maj Institute of Pharmacology Polish Academy of Sciences.)

Tebuconazole (TEB), a widely used pesticide in agriculture to combat fungal infections, is commonly detected in global food, potable water, groundwater, and human urine samples. Despite its known in vivo toxicity, its impact on heart function remains unclear. In a 28-day study on male Wistar rats (approximately 100 g), administering 10 mg/kg/day TEB or a vehicle (control) revealed no effect on body weight gain or heart weight, but an increase in the infarct area in TEB-treated animals. Notably, TEB induced time-dependent changes in in vivo electrocardiograms, particularly prolonging the QT interval after 28 days of administration. Isolated left ventricular cardiomyocytes exposed to TEB exhibited lengthened action potentials and reduced transient outward potassium current. TEB also increased reactive oxygen species (ROS) production in these cardiomyocytes, a phenomenon reversed by N-acetylcysteine (NAC). Furthermore, TEB-treated animals, when subjected to an in vivo dobutamine (Dob) and caffeine (Caf) challenge, displayed heightened susceptibility to severe arrhythmias, a phenotype prevented by NAC. In conclusion, TEB at the no observed adverse effect level (NOAEL) dose adversely affects heart electrical function, increases arrhythmic susceptibility, partially through ROS overproduction, and this phenotype is reversible by scavenging ROS with NAC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Clinical Impact: When the standard endovascular crossing maneuvers have failed during CLTI recanalization procedures and the distal below-the-knee or proximal below-the-ankle retrograde access is not possible due to chronic occlusion of the vessels, mastering the more distal and complex retrograde BTA punctures may be advantageous.There are scanty reports regarding the retrograde puncture of the mid and forefoot vessels. The aim of this article is to review different tips and tricks related to these techniques to help operators to apply them in specific scenarios to eventually improve procedural success rate., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Amiodarone (AMD) is a clinically used drug to treat arrhythmias with significant effect upon the cardiac sodium channel Na v 1.5. AMD has a pKa of 6.56, and changes in extracellular pH (pHe) may alter its pharmacological properties. Here we explored how changes in pHe impacts the pharmacological properties of AMD upon human-Na v 1.5-sodium-current (I Na ) and in ex vivo rat hearts., Methods: Embryonic-human-kidney-cells (HEK293) were used to transiently express the human alpha-subunit of Na V 1.5 channels and the isolated heart of Wistar rats were used. Patch-Clamp technique was deployed to study I Na and for electrocardiogram (ECG) evaluation the ex vivo heart preparation in the Langendorff system was applied., Results: The potency of AMD upon peak I Na was ∼25x higher in pHe 7.0 when compared to pHe 7.4. Voltage dependence for activation did not differ among all groups. AMD shifted the steady-state inactivation curve to more hyperpolarized potentials, with similar magnitudes for both pHes. The recovery from I Na inactivation was delayed in the presence of AMD with similar profile in both pHes. Interestingly, the use-dependent properties of AMD was distinct at pHe 7.0 and 7.4. Finally, AMD was able to change the ex vivo ECG profile, however at pHe 7.0+AMD a larger increase in the RR and QRS duration and in the QT interval when compared to pHe 7.4 was found., Conclusions: The pharmacological properties of AMD upon Na V 1.5 and isolated heart preparation depends on the pHe and its use in vivo during extracellular acidosis may cause a distinct biological response in the heart tissue., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests, conflict of interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The TASK-1 channel belongs to the two-pore domain potassium channel family. It is expressed in several cells of the heart, including the right atrial (RA) cardiomyocytes and the sinus node, and TASK-1 channel has been implicated in the pathogenesis of atrial arrhythmias (AA). Thus, using the rat model of monocrotaline-induced pulmonary hypertension (MCT-PH), we explored the involvement of TASK-1 in AA. Four-week-old male Wistar rats were injected with 50 mg/kg of MCT to induce MCT-PH and isolated RA function was studied 14 days later. Additionally, isolated RA from six-week-old male Wistar rats were used to explore the ability of ML365, a selective blocker of TASK-1, to modulate RA function. The hearts developed right atrial and ventricular hypertrophy, inflammatory infiltrate and the surface ECG demonstrated increased P wave duration and QT interval, which are markers of MCT-PH. The isolated RA from the MCT animals showed enhanced chronotropism, faster contraction and relaxation kinetics, and a higher sensibility to extracellular acidification. However, the addition of ML365 to extracellular media was not able to restore the phenotype. Using a burst pacing protocol, the RA from MCT animals were more susceptible to develop AA, and simultaneous administration of carbachol and ML365 enhanced AA, suggesting the involvement of TASK-1 in AA induced by MCT. TASK-1 does not play a key role in the chronotropism and inotropism of healthy and diseased RA; however, it may play a role in AA in the MCT-PH model., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Atrial arrhythmias (AA) are common in pulmonary hypertension (PH) and are closely associated with poor clinical outcomes. One of the most studied models to investigate PH is the rat model of monocrotaline (MCT) induced PH (MCT-PH). To date, little is known about right atrium (RA) function in the MCT-PH model and the propensity of RA to develop arrhythmias. Therefore, the aim of the study was to evaluate the function of the RA of control (CTRL) and MCT treated rats, and the ability of amiodarone, a classical antiarrhythmic, to prevent the occurrence of AA in the RA in MCT-PH rats. RA function was studied in MCT-PH rats 20 days after a single subcutaneous injection of MCT 50 mg/kg. The histological results indicated the presence of RA and right ventricular hypertrophy. Surface electrocardiogram demonstrated increased P wave duration, PR wave duration and QT interval in MCT rats. RA from MCT rats were more susceptible to develop ex vivo burst pacing arrhythmias when compared to CTRL. Intriguingly, amiodarone in clinical relevant concentration was not able to prevent the occurrence arrhythmias in RA from MCT-PH animals. Hence, we conclude that the rat model of MCT-PH impairs RA structure and function, and acute exposure of RA to amiodarone in clinical relevant concentration is not able to attenuate the onset of arrhythmias in the ex vivo RA preparation., (© 2023 John Wiley & Sons Australia, Ltd.)

Eugenol is an aromatic compound used in the manufacture of medicines, perfumes, cosmetics and as an anaesthetic due to the ability of the drug to block the neuronal isoform of voltage-gated Na + channels (Na V ). Some arrhythmias are associated with gain of function in the sodium current (I Na ) found in cardiomyocytes, and antiarrhythmic sodium channel blockers are commonly used in the clinical practice. This study sought to elucidate the potential mechanisms of eugenol's protection in the arrhythmic model of ouabain-induced arrhythmias in guinea pig heart. Ex vivo arrhythmias were induced using 50 μM of ouabain. The antiarrhythmic properties of eugenol were evaluated in the ex vivo heart preparation and isolated ventricular cardiomyocytes. The compound's effects on cardiac sodium current and action potential using the patch-clamp technique were evaluated. In all, eugenol decreased the ex vivo cardiac arrhythmias induced by ouabain. Furthermore, eugenol showed concentration dependent effect upon peak I Na , left-shifted the stationary inactivation curve and delayed the recovery from inactivation of the I Na . All these aspects are considered to be antiarrhythmic. Our findings demonstrate that eugenol has antiarrhythmic activity, which may be partially explained by the ability of eugenol to change de biophysical properties of I Na of cardiomyocytes., (© 2023 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society). Published by John Wiley & Sons Ltd.)

The fungicide Tebuconazole is a widely used pesticide in agriculture and may cause cardiotoxicity. In our present investigation the effect of Tebuconazole on the sodium current (I Na ) of human cardiac sodium channels (Na V 1.5) was studied using a heterologous expression system and whole-cell patch-clamp techniques. Tebuconazole reduced the amplitude of the peak I Na in a concentration- and voltage-dependent manner. At the holding potential of -120 mV the IC 50 was estimated at 204.1 ± 34.3 μM, while at -80 mV the IC 50 was 0.3 ± 0.1 μM. The effect of the fungicide is more pronounced at more depolarized potentials, indicating a state-dependent interaction. Tebuconazole caused a negative shift in the half-maximal inactivation voltage and delayed recovery from fast inactivation of I Na . Also, it enhanced closed-state inactivation, exhibited use-dependent block in a voltage-dependent manner. Furthermore, Tebuconazole reduced the increase in late sodium current induced by the pyrethroid insecticide β-Cyfluthrin. These results suggest that Tebuconazole can interact with Na V 1.5 channels and modulate I Na . The observed effects may lead to decreased cardiac excitability through reduced I Na availability, which could be a new mechanism of cardiotoxicity to be attributed to the fungicide., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Danilo Roman Campos, corresponding author, signing on the behalf of all authors., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: The high incidence of atrial arrhythmias in pulmonary hypertension (PH) might be associated with poor prognosis, and the left atrium (LA) may play a role in this. An important finding in PH studies is that LA remodeling is underestimated., Objective: This study investigated LA morphology and mechanical function, as well as the susceptibility to develop arrhythmias in a monocrotaline-induced PH (MCT-PH) model., Methods: Wistar rats aged 4 weeks received 50 mg/kg of MCT. Electrocardiography and histology analysis were performed to evaluate the establishment of the MCT-PH model. The tissue was mounted in an isolated organ bath to characterize the LA mechanical function., Results: Compared with the control group (CTRL), the MCT-PH model presented LA hypertrophy and changes in cardiac electrical activity, as evidenced by increased P wave duration, PR and QT interval in MCT-PH rats. In LA isolated from MCT-PH rats, no alteration in inotropism was observed; however, the time to peak contraction was delayed in the experimental MCT-PH group. Finally, there was no difference in arrhythmia susceptibility of LA from MCT-PH animals after the burst pacing protocol., Conclusion: The morphofunctional remodeling of the LA did not lead to increased susceptibility to ex vivo arrhythmia after application of the burst pacing protocol.

A new decyl chain [-(CH 2 ) 9 CH 3 ] riboflavin conjugate has been synthesized and investigated. A nucleophilic substitution (S N 2) reaction was used for coupling the alkyl chain to riboflavin (Rf), a model natural photosensitizer. As expected, the alkylated compound (decyl-Rf) is significantly more lipophilic than its precursor and efficiently intercalates within phospholipid bilayers, increasing its fluorescence quantum yield. The oxidative damage to lipid membranes photoinduced by decyl-Rf was investigated in large and giant unilamellar vesicles (LUVs and GUVs, respectively) composed of different phospholipids. Using a fluorogenic probe, fast radical formation and singlet oxygen generation was demonstrated upon UVA irradiation in vesicles containing decyl-Rf. Photosensitized formation of conjugated dienes and hydroperoxides, and membrane leakage in LUVs rich in poly-unsaturated fatty acids were also investigated. The overall assessment of the results shows that decyl-Rf is a significantly more efficient photosensitizer of lipids than its unsubstituted precursor and that the association to lipid membranes is key to trigger phospholipid oxidation. Alkylation of hydrophilic photosensitizers as a simple and general synthetic tool to obtain efficient photosensitizers of biomembranes, with potential applications, is discussed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Atrial arrhythmias are a hallmark of heart diseases. The antiarrhythmic drug ranolazine with multichannel blocker properties is a promising agent to treat atrial arrhythmias. We therefore used the rat model of monocrotaline-induced pulmonary-hypertension to assess whether ranolazine can reduce the incidence of ex vivo atrial arrhythmias in isolated right atrium. Four-week-old Wistar rats were injected with 50 mg/kg of monocrotaline, and isolated right atrium function was studied 14 days later. The heart developed right atrium and right ventricular hypertrophy, and the ECG showed an increased P wave duration and QT interval, which are markers of the disease. Moreover, monocrotaline injection caused enhanced chronotropism and faster kinetics of contraction and relaxation in isolated right atrium. Additionally, in a concentration-dependent manner, ranolazine showed chronotropic and ionotropic effects upon isolated right atrium, with higher potency in the control when compared with experimental model. Using a burst pacing protocol, the isolated right atrium from the monocrotaline-treated animals was more susceptible to develop arrhythmias, and ranolazine was able to attenuate the phenotype. Thus, we concluded that the rat model of monocrotaline-induced pulmonary-hypertension develops right atrium remodelling, which increased the susceptibility to present ex vivo atrial arrhythmias, and the antiarrhythmic drug ranolazine ameliorated the phenotype., (© 2023 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society). Published by John Wiley & Sons Ltd.)

Here, we provide mechanistic insight to the photocleavage of a compound in the folate family, namely pteroic acid. A bis-decyl chain derivative of pteroic acid was synthesized, structurally characterized and photochemically investigated. We showed that, like folic acid, pteroic acid and the decylated derivative undergo a photocleavage reaction in the presence of H 2 O, while no reaction was observed in methanol solution. Furthermore, density functional theory calculations were carried out to predict relative stabilities of hypothetical mono-, bis- and tris-decylated pteroic acid derivatives to help rationalize the regioselectivity of the bis-decyl pteroic acid product. Additionally, the lipophilicity of the bis-decyl pteroic acid appears to confer a hydrophobic property enabling an interaction with biomembranes., (© 2022 American Society for Photobiology.)

Purpose: To describe a novel bailout technique to approach below-the-knee chronic total occlusions after a failed bidirectional recanalization attempt using the plantar loop maneuver in patients who are poor candidates for a retrograde puncture., Technique: After a failure of recanalization of the opposite tibial artery using the plantar loop maneuver, an assisted direct retrograde transpedal approach can be performed regardless of poor vessel caliber or even arterial occlusion. After crossing the plantar arch, a low profile angioplasty balloon is used as a landmark for the pedal puncture and to give guidance for the wire advancement from the new access., Conclusion: A balloon-assisted retrograde transpedal approach may be considered for below-the-knee recanalization after standard plantar loop technique failure in patients who are not candidates for conventional retrograde puncture.

The physical properties of lipid membranes depend on their lipid composition. Photosensitized singlet oxygen ( 1 O 2 ) provides a handle to spatiotemporally control the generation of lipid hydroperoxides via the ene reaction, enabling fundamental studies on membrane dynamics in response to chemical composition changes. Critical to relating the physical properties of the lipid membrane to hydroperoxide formation is the availability of a sensitive reporter to quantify the arrival of 1 O 2 . Here, we show that a fluorogenic α-tocopherol analogue, H 4 BPMHC, undergoes a >360-fold emission intensity enhancement in liposomes following a reaction with 1 O 2 . Rapid quenching of 1 O 2 by the probe ( k q = 4.9 × 10 8 M -1 s -1 ) ensures zero-order kinetics of probe consumption. The remarkable intensity enhancement of H 4 BPMHC upon 1 O 2 trapping, its linear temporal behavior, and its protective role in outcompeting membrane damage provide a sensitive and reliable method to quantify the 1 O 2 flux on lipid membranes. Armed with this probe, fluorescence microscopy studies were devised to enable (i) monitoring the flux of photosensitized 1 O 2 into giant unilamellar vesicles (GUVs), (ii) establishing the onset of the ene reaction with the double bonds of monounsaturated lipids, and (iii) visualizing the ensuing collective membrane expansion dynamics associated with molecular changes in the lipid structure upon hydroperoxide formation. A correlation was observed between the time for antioxidant H 4 BPMHC consumption by 1 O 2 and the onset of membrane fluctuations and surface expansion. Together, our imaging studies with H 4 BPMHC in GUVs provide a methodology to explore the intimate relationship between photosensitizer activity, chemical insult, membrane morphology, and its collective dynamics.

Aims: Eugenol is a natural compound found in the essential oils of many aromatic plants. The compound is used as a local anesthetic because of its inhibitory effect on the voltage-gated Na + channels (Na v ), which are expressed in the nociceptive neurons. Eugenol has shown wide range of activities in the cardiovascular system; most of these activities are attributed to the modulation of voltage-sensitive Ca 2+ channels. However, its action on Na v 1.5, the main subtype of Na v expressed in the mammalian myocardium, is unknown. The interaction of eugenol with Na v 1.5 could also contribute to its antiarrhythmic properties in vitro and ex vivo. We investigated the compound's effect on sodium current (I Na ) and its possible cardiac antiarrhythmic activity., Methods: The effect of eugenol on cardiac contractility was investigated using isolated atrium from guinea pig (for isometric force measurements). The compound's effect on I Na was evaluated using human embryonic cell transiently expressing human Nav1.5 and patch-clamp technique., Key Findings: Eugenol caused negative inotropic and chronotropic effects in the atria. In the ex vivo arrhythmia model, eugenol decreased atrial pacing disturbance induced by ouabain. Eugenol reduced the I Na in a concentration-dependent manner. Furthermore, the compound left-shifted the stationary inactivation curve, delayed recovery from inactivation of the I Na , and preferentially blocked the channel in the inactivated state. Importantly, eugenol was able to attenuate the late sodium current. All these aspects are considered to be antiarrhythmic., Significance: Overall, our findings demonstrate that eugenol has antiarrhythmic activity due, at least in part, to its interaction with Na v 1.5., (Copyright © 2021 Elsevier Inc. All rights reserved.)

An important group of antiemetic drugs used in the treatment of nausea and vomiting after chemotherapy containing an indole moiety in their structures, working as 5- hydroxytryptamine type 3 serotonin receptor antagonist (5-HT3). This study focuses on compounds bearing an indole core that present a 5-HT3 receptor antagonist activity, which have been successfully used as antiemetic drugs for reducing chemotherapy adverse secondary effects during cancer treatment. Their synthesis, biological activities, and some outstanding characteristics are discussed, providing a general outlook towards the development of more efficient antiemetic drugs., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Purpose: To present a simple method to avoid favored passage of a guidewire into the profunda femoris artery (PFA) after antegrade puncture of the common femoral artery. Technique: A 6-F conventional introducer sheath with a radiopaque distal marker is placed on the nurse's table with its side port orientated to the 12 o'clock position. A small (2-2.5 mm) oval fenestration is created on the superior aspect of the sheath about 3 cm from its tip with a size 11 surgical blade. The modified introducer is passed over the angled 0.035-inch guidewire into the PFA and gently retrieved until the tip marker is ~3 cm from the femoral bifurcation. The dilator is removed, and the guidewire is withdrawn to the level of the fenestration, manipulated through it, and advanced further into the superficial femoral artery under fluoroscopic guidance. Conclusion: When repeated passage of the guidewire down the PFA persists despite conventional manipulation of the wire or needle, an on-site modification of the sheath is an easy alternative approach for the catheterization of the superficial femoral artery.

A case of a femoropopliteal recanalization procedure using a new bailout technical maneuver to aid reentry into the true lumen is described. After a failed standard reentry attempt, at the level of the vessel reconstitution in the subintimal space, the guidewire was exchanged for a GooseNeck Snare Kit. A needle was inserted across the target artery, piercing both arterial walls and passing through the snare loop. Once the needle had exited the artery, a wire was inserted and the needle withdrawn. The snare was closed, withdrawn, and the wire externalized through the femoral access. Finally, a catheter was advanced from the antegrade sheath up to the arterial reconstitution. Selective injection at the site of reentry confirmed the intraluminal position, and the procedure was successfully completed from the antegrade sheath., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the efficacy of a new guidewire threading instrument (GTI) in reducing guidewire threading times compared with the traditional freehand method., Materials and Methods: This prospective, controlled, single-center study recruited 100 subjects (mean age 45.2±11.3 years; 43 men) and divided them into 2 groups depending on their professional background: 50 experienced medical personnel (performed or assisted in >50 catheter-based procedures) and 50 medical personnel with no experience in endovascular techniques (inexperienced group). The threading time of both groups was recorded using the conventional freehand method and with the GTI for both 0.035- and 0.014-inch platforms. Users of eyeglasses for presbyopia were tested with and without glasses. Median values are reported with the interquartile range (IQR; Q1, Q3) in parentheses., Results: The mean insertion times with both the 0.035-inch and 0.014-inch guidewires in the overall study group were significantly better with the use of the GTI compared with the traditional freehand method (p<0.001). Both the experienced and the inexperienced participants improved their insertion times using the GTI with both guidewire platforms (p<0.001). The threading time with the new device was also significantly reduced (p<0.001) for both participants with presbyopia and those without. When comparing the median absolute time improvement (difference between freehand/GTI insertion times) for the 0.014-inch platform, the inexperienced group showed a greater improvement in their performance [3.52 seconds (IQR 2.76, 5.12)] compared with the experienced group [1.87 seconds (IQR 1.37, 2.66), p<0.001]. The median "absolute time improvement" was also significantly greater for the presbyopic group [5.75 seconds (IQR 3.14, 8.20)] vs the group without age-related visual impairment [2.64 seconds (IQR 1.65, 3.36), p<0.001]., Conclusion: This simple and inexpensive homemade device facilitates wire threading of low-profile catheters and seems to be especially helpful for trainees with no experience and presbyopic operators.

Purpose: To describe a maneuver to facilitate percutaneous arteriovenous fistula creation during venous arterialization procedures in patients with no-option critical limb ischemia., Technique: Following a failed arterial recanalization attempt, a balloon catheter is passed up to the tip of the guidewire. Venous access is gained distally, a 4-F sheath is antegradely passed, and a 4-mm GooseNeck snare is advanced through it. A fluoroscopic view that overlaps the snare and the inflated balloon is obtained. If the vein remains anterior with respect to the artery, a needle is inserted across the vein, passing through the snare loop and puncturing the intra-arterial balloon. A wire is inserted and placed inside the punctured balloon. The balloon is retrieved and the wire externalized through the femoral access. A catheter is advanced antegradely over this wire from the artery into the vein. If the vein remains posterior to the artery, a needle is inserted, puncturing the balloon and thereafter the vein (crossing through the snare). A wire is inserted, captured by the snare, and externalized through the vein sheath. A catheter is finally advanced over this wire from the vein into the artery., Conclusion: This maneuver is a simple alternative to create an arteriovenous fistula during venous arterialization procedures in patients with no-option critical limb ischemia.

Objetive: Coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB) improved symptoms and increased survival and quality of life in patients with coronary artery disease. However, it should be the main cause of a complex organic systemic inflammatory response that greatly contributes to several postoperative adverse effects., Methods: We aimed to evaluate heat-shock protein 70 (HSP 70) expression as a morbimortality predictor in patients with preserved ventricular function undergoing coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB) and to determine their association with the lactate as a marker of tissue hypoperfusion and the EuroSCORE risk score. This is a prospective, observational study including 46 patients and occurring between May and July 2016. Patients without ventricular dysfunction undergoing myocardial revascularization with extracorporeal circulation were included. They were divided into (1) complicated and (2) uncomplicated postoperative evolution groups. EuroSCORE, lactate levels, and HSP 70 expression and their correlations were determined., Results: Statistical analysis showed that the group with complicated evolution had higher EuroSCORE values than the other group. HSP 70 protein levels were significantly increased in the group with uncomplicated evolution and showed similar results. According to our results, HSP family proteins may be independent predictors of uncomplicated evolution in patients without ventricular dysfunction undergoing CABG with CPB., Conclusion: HSP 70 should be a good discriminator and protection marker for complications in cardiac surgery.

Purpose: To describe a simple maneuver to facilitate the retrograde puncture of challenging tibial vessels in the lower leg., Technique: Because of the depth of the tibial vessels at the mid to upper calf, especially in obese or muscular patients, a 7- or 9-cm, 21-G micropuncture needle is often needed to reach the artery. However, the low profile of the needle contributes to its flexibility and therefore the tendency to bend as it progresses through the deep tissues, hindering access to the target vessel. To overcome this obstacle, a 4- to 5-cm, 18-G needle is initially placed pointing to the artery. The 21-G needle is advanced through it to the target site. This simple maneuver increases the support to the 21-G needle, preventing its bending and facilitating arterial puncture in the presence of calcified vessels., Conclusion: The telescoping needle technique may be considered as a bailout procedure in the retrograde tibial approach after failed attempts secondary to needle bending or calcified vessels.

Purpose: To describe a technical trick to overcome a prior failed retrograde puncture of the tibial vessels secondary to arterial calcification., Technique: Following a prior failed retrograde puncture attempt, the needle is left in place next to the artery. The tip of the needle is then moved toward the artery as a lever so that the artery is fixed between the needle, the skin, and the surrounding tissues. With the artery fixed, a standard puncture procedure is performed. Alternatively, if additional support is needed, 2 micropuncture needles are inserted one on either side of the artery, crossing under the target vessel and hence trapping it between them, providing additional support and therefore enhancing the chance of successful arterial access., Conclusion: The buddy needle technique may be considered as an alternative procedure in a retrograde pedal/tibial approach after prior failed standard attempts in patients with heavily calcified vessels.

Pathology related to the rotator cuff remains among the most prevalent musculoskeletal diseases. There is an increasing need for imaging studies (MRI, US, arthroscopy) to test the diagnostic performance of the medical history and physical examination., Objective: To prove the diagnostic value of a clinical-radiographic predictive model to find complete ruptures of the rotator cuff., Material and Methods: Descriptive, observational, prospective, transversal and analytical study. Fifty-five patients with preoperative shoulder pain were evaluated with 13 predictive variables: age > 50 years, nocturnal pain, muscle weakness, clinical signs of Neer, Hawkins, Jobe, external rotation lag (ERLS), belly-press, bear hug, and lift-off, radiographic measurement of subacromial space, acromial index and critical shoulder angle. Sensitivity, specificity, and positive and negative predictive values were measured in each variable, comparing the results of each one against the postoperative findings., Results: Of the 55 patients evaluated, 42 had a complete rupture of the rotator cuff in the postoperative period. The eight variables with a higher diagnostic value were selected and a ROC curve was performed, providing an area under the curve of 0.88., Conclusions: This predictive model uses eight variables (age > 50 years, nocturnal pain, muscle weakness, Jobe, Hawkins, ERLS, subacromial space ≤ 6 mm, and critical shoulder angle > 35°), which together add the predictive value of 0.88 (AUC) to diagnose complete ruptures of the supraspinatus tendon.

Chronic cold stress produces adrenergic overload that can affect fetal development. The placental norepinephrine transporter (NET) clears norepinephrine (NE) from both maternal circulation and the fetus during gestation. If this system fails, NE clearance can be reduced, leading to high fetal exposure to NE. The main aim of this study was to determine the changes in NET expression during gestation and their relationship with the functional capacity of NET to transport NE under stressful conditions. Additionally, this study correlated these findings with the reproductive capacity of 2nd-generation progeny. Pregnant rats were subjected to chronic cold stress at 4°C for 3 h each day throughout their pregnancies. We found that exposure of pregnant rats to sympathetic stress caused the following effects: increased NE and corticosterone levels throughout pregnancy, decreased capacity of the placenta to clear NE from the fetus to the mother's circulation, altered NET protein levels depending on the sex of the fetus and increased placental and body weights of pups. For the first time, we also described the disrupted fertility of progeny as adults. Increased NE plasma levels during pregnancy under sympathetic stress conditions correlated with decreased NET functionality that provoked changes in the development of progeny and their fertility in adulthood., (© 2017 Society for Reproduction and Fertility.)

The authors present a surgical approach to type III and IV Crawford aneurysms that does not need total aortic clamping, which allows the more objective prevention of direct ischemic damage, as well as its exclusion by the endoprosthesis implantation, shunting the flow to the synthetic graft.

Antegrade puncture is a routinely used technique of obtaining access to the common femoral artery to perform infrainguinal interventions. However, antegrade arterial access can be challenging in the presence of hostile, scarred groins, obesity, or a high common femoral artery bifurcation. A simple method of converting a retrograde femoral access to an antegrade catheterization using an inexpensive and universally available monofilament suture is presented., (Copyright © 2014 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

In this work we used rheometry and DLS to probe relaxation phenomena in solutions of chitosan and octa-ethyleneglycol-monododecylether. The dispersions had a marked pseudoplastic behavior, which became less evident, as surfactant concentration was increased. Arrhenius plots showed that systems with surfactant presented a characteristic temperature at which apparent enthalpy of activation (varying from 3 to 40 kJ mol(-1)) changed: this change was correlated to a possible transition of colloidal aggregates to a wormlike configuration. DLS intensity correlation functions were described by KWW equation: pure chitosan solutions had relaxation rate distributions centered at a characteristic relaxation rate around 4.6×10(-6) μS(-1); as surfactant was added, a new component, with a faster characteristic relaxation rate with a magnitude order of 10(-3) μs(-1), appeared. It was shown that the dependence between these relaxation rates and surfactant concentration could be used to describe DLS-related relaxation phenomena as an Arrhenius-activated process, agreeing with results obtained using rheometry., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Chitosan has more and more been suggested as a material for use as adsorbent in the treatment of effluents as well as in the synthesis of drug-loaded nanoparticles for controlled release. In both cases, a good understanding of the process of adsorption, both kinetically and in terms of equilibrium, has an importance of its own. In this manuscript we study the interaction between sodium cromoglycate, a drug used in asthma treatment, and chitosan. Equilibrium experiments showed that Sips (or Freundlich-Langmuir) isotherm described well the resultant data and adsorption possibly occurred as in multilayers. A model based on ordinary reaction-rate theory, compounded of two processes, each one with a correlated velocity constant, described the kinetics of sorption. Kinetic and equilibrium data suggested the possibility of surface rearrangement, favored by the increase of temperature., (Copyright © 2013 Elsevier B.V. All rights reserved.)

In the era of greatly improved pharmacological treatment of HIV infection through highly active antiretroviral therapy (HAART), HIV patients experience reduced viral loads, reduced opportunistic infections, increased CD4+ T cell count, and greater life expectancy. Although life expectancy is increased, patients often develop neurological disturbances that may persist for long periods, seriously jeopardizing quality of life and adherence to the medication protocols of HAART. For these reasons, HIV-associated neurological disorders have gained importance in both clinical and basic investigations of HIV infection. Depression is the most prevalent neuropsychiatric disorder among people living with HIV. In this review, we discuss how HIV can predispose infected individuals to depression by several interrelated mechanisms. These include inducing chronic elevation of cytokines through activation of microglia and astrocytes; decreasing monoaminergic function; inducing neurotoxicity, especially in dopaminergic neurons; and reducing brain-derived neurotrophic factor. These viral pathways interact with psychosocial factors to create the depressive state. HIV depression has a great impact on quality of life and implementation of antiretroviral therapy, and thus, recognition of these modes of action is significant for understanding HIV neuropathology and for selecting modalities for pharmacologic treatment.

Several species of scorpions are known to cause accidents which can lead to death, most of them belonging to the genus Tityus. Tityus serrulatus is considered the most dangerous scorpion in South America. In Brazil, T. serrulatus is responsible for serious accidents, including deaths, which occur mainly with children and elderly people. Anti-scorpion sera are routinely produced by various institutions, and suitable technologies have been investigated for encapsulation and release recombinant or native proteins capable of inducing antibody production. In this context, biocompatible and biodegradable polymers, such as chitosan, have been employed for this purpose. This study aimed to obtain a protein release system for the peptides or proteins from T. serrulatus, based on cross-linked chitosan nanoparticles (CN) in order to generate a new model of immunization in animals, and consequently a potentially novel polyclonal serum, namely an anti-T. serrulatus venom. CN were successfully obtained by ionic gelation using the polyanion tripolyphosphate (TPP), which demonstrated a suitable particle size of about 200 nm, with maximum encapsulation efficiency (100%) and enhanced antigen-specific antibody titers of 72%. The serum production data revealed that CN were equipotent to aluminum hydroxide, the traditional adjuvant for immunization. This study demonstrates that chitosan nanoparticles are a promising and safe system for peptide/protein delivery for T. serrulatus scorpion., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Adsorption phenomena occurring at the solid/liquid interface of chitosan particles are of extreme importance in the kinetics of drug release/upload as well as in effluent treatment by adsorption. In this work, equilibrium and kinetic aspects of protonated tetracycline adsorption on chitosan are explored using classic solution depletion method and zeta potential measurements. Equilibrium experiments showed that for solutions with tetracycline initial concentration of ca. 1.2 g L(-1), corresponding to a pH around 3, chitosan structure disrupted, as indicated by an increase in magnitude of tetracycline sorption. Adsorption and zeta potential isotherms before disruption suggested that the process of adsorption had a Langmuir character up to a point at which subsurface was exposed to adsorption; at this point, a second mode of sorption began: zeta potential tended to an equilibrium value, following Sips isotherm and tetracycline sorption had a linear dependence on its continuous phase concentration. The kinetics of tetracycline sorption suggested that sorption of tetracycline was divided between the sorption of protonated and non-protonated tetracycline; tetracycline in its non-protonated form seemed to rule the sorption of tetracycline., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Chitosan nanoparticles have been used in several systems destined to controlled release of active agents. In this manuscript the process of formation of chitosan nanoparticles, obtained employing the coacervation method with sodium sulfate is analyzed using zeta potential and small angle X-ray scattering (SAXS) measurements. Dispersions were obtained at pH=1 and pH=3 and presented a behavior, in terms of surface charging, that was independent of pH. However, SAXS results indicated a dependence of size-related behavior on pH. The difference in terms of behavior was explained through the influence of enthalpic and entropically driven components., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Solutions of chitin in Li(+)/N,N-dimethylacetamide systems were studied via viscometry, using LiCl concentrations of 3% and 5% (m/v) and chitin concentrations ranging from 0.075 to 0.375 gL(-1). The reduced viscosity number versus concentration plot showed a minimum that was related to the formation of Li(+)-OC complex moieties along chitin macromolecular chains. Viscosity behavior was affected by temperature according to the Eyring model: concentration dependence of flow enthalpy of activation was correlated to polymer-polymer interactions and flow entropy of activation to the stiffness of the complexed chitosan macromolecular chain., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: We describe a simple method to avoid favored passage of the wire into the profunda femoral artery (PFA) after antegrade puncture of the common femoral artery., Methods: The method consists of placing a 3F Fogarty catheter into the origin of the PFA, which addresses the guidewire toward the superficial femoral artery., Conclusion: When a repeated passage of the guidewire down the PFA is experienced despite conventional manipulation of the wire or needle, the barrier technique is an easy alternative approach for the catheterization of the superficial femoral artery., (Copyright 2010 Annals of Vascular Surgery Inc. Published by Elsevier Inc. All rights reserved.)

Persistent sciatic artery (PSA) is a very uncommon congenital malformation. Its incidence is estimated to be 0.025-0.04%. If it is accompanied by hypoplasia of the femoral artery system, its presence is essential for perfusion of the limbs. The usual form of presentation is as an aneurysm (25-58%) and/or its complications (thrombosis, distal remobilization, local compression). A 66-year-old woman presented with a painful mass of several months' progression. After performing angio-computed tomography, a fusiform aneurysmal dilation was observed in the left gluteal mass dependent on the left obturator artery, which was identified as the left lower gluteal artery. For this reason, we decided to perform therapeutic embolization. During the angiogram, a left aneurysmal PSA with distal thrombosis was observed. In view of these findings, a bypass from the superficial femoral artery to the tibioperoneal trunk was performed, with a contralateral inverted saphenous vein. The PSA was subsequently embolized with an occluder (AGA Medical IZASA, Plymouth, MN). The patient was discharged after checking complete exclusion of the aneurysm by ultrasound, with distal pulses during follow-up. Combined treatment using embolization, before surgical revascularization of the limb, markedly decreases the morbidity and mortality by avoiding the pelvic approach by the posterior route., (Copyright (c) 2010 Annals of Vascular Surgery Inc. Published by Elsevier Inc. All rights reserved.)

Experiments to monitor and characterize the kinetics of adsorption of tetracycline on chitosan particles are reported in this work. The same pseudo-order kinetics that has been widely used for describing the adsorption in systems related to wastewater purification and drug loading was used to treat the present data. As some unexpected results came out from the experiments, it was necessary a detailed deduction for this sort of kinetics to be carried out, so that approximations related to short and long times were obtained. Firstly it was shown that an apparently linear t/q(t) versus t relationship did not imply a pseudo-second-order sorption kinetics, differently of what has been repeatedly reported in the literature. It was found that this misinterpretation could be avoided by using non-linear regression. Finally, the adsorption of tetracycline on chitosan particles was analyzed, using the insights obtained from theoretical analysis, and the parameters generated were used to analyze to adsorption kinetics and to propose an adsorption mechanism.

Chitosan is a polysaccharide used in a broad range of applications. Many of its unique properties come from the presence of amino groups in its structure. A proper quantification of these amino groups is very important, in order to specify if a given chitosan sample can be used in a particular application. In this work, a comparison between the determination of chitosan degree of deacetylation by conductometry and CHN elemental analysis was carried out, using a rigorous error analysis. Accurate expressions relating CHN composition, conductometric titration, and degree of deacetylation, in conjunction with their associated errors, were developed and reported in this note. Error analysis showed conductometric analysis as an inexpensive and secure method for the determination of the degree of deacetylation of chitosan.

In this work chitosan membranes modified by contact with poly(acrylic acid) (PAA) aqueous solution at two different temperatures (25 degrees C and 60 degrees C) were obtained. The pure chitosan (CS) membranes, as well as those treated with PAA (CSPAA&#95;25 and CSPAA&#95;60) were characterized by FTIR-ATR, water sorption capacity, thermal analysis (TG/DTG), and scanning electron microscopy (SEM). In addition, in vitro permeation experiments were carried out using metronidazol and sodium sulfamerazine aqueous solutions at 0.1% and 0.2% as model drugs. FTIR-ATR results showed the presence of absorption bands of NH3+ and COO(-) indicating the formation of a polyelectrolyte complex between chitosan and poly(acrylic acid). The results also indicated that PAA penetrates deeper into the membrane at higher temperature (60 degrees C), forming a thicker complex layer. Polyelectrolyte complex formation as well as the influence of treatment temperature was confirmed by lower hydrophilicity, higher thermal stability, and lower permeability of the treated membranes. The results show that the methodology used is a simple and very efficient way to drastically change some membrane properties, especially their permeability.