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Essential oils (EOs) have antimicrobial properties, but their low solubility in water and strong flavor pose challenges for direct incorporation into food, as they can negatively impact organoleptic properties. To overcome these issues, strategies such as oil-in-water (O/W) nanoemulsions have been developed to improve EO dispersion and protection while enhancing antimicrobial efficacy. The objective of this study was to create sodium alginate-pink pepper essential oil (PPEO) nanoemulsions using microfluidization. Various formulations were assessed for physicochemical, physical, and antimicrobial properties to evaluate their potential in food applications. The microfluidized emulsions and nanoemulsions had droplet sizes ranging from 160 to 443 nm, polydispersity index (PdI) ranging from 0.273 to 0.638, and zeta potential (ζ) ranging from -45.2 to 66.3 mV. The nanoemulsions exhibited Newtonian behavior and remarkable stability after 20 days of storage. Antimicrobial testing revealed effectiveness against Staphylococcus aureus and Listeria monocytogenes, with minimum inhibitory concentrations (MIC) of 200 µg/mL for both microorganisms and minimum bactericidal concentrations (MBC) of 800 µg/mL and 400 µg/mL, respectively, proving that encapsulation of PPEO in nanoemulsions significantly increased its antibacterial activity. These results present the possibility of using PPEO nanoemulsions as a more effective natural alternative to synthetic preservatives in food systems.
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Valproic acid (VA) is a widely used drug for the treatment of diseases affecting the central nervous system. Due to its epigenetic modulatory potential, it has been studied for possible therapeutic application in anticancer therapies. However, the VA exhibits different side effects in its application. Thus, synthetic coordination complexes with valproate can generate promising candidates for new active drugs with reduced toxicity. In this sense, we investigated the genotoxic and mutagenic potential of the sodium valproate and of the mixed ternary mononuclear Mg complex based on VA with 1,10-phenanthroline (Phen) ligand - [Mg (Valp)2Phen], in Saccharomyces cerevisiae and V79 cells. The MTT and clonal survival assays in V79 cells indicated that the Mg complex has higher cytotoxicity than sodium valproate. A similar cytotoxicity profile is observed in yeast. This fact is possibly due to the intercalation capacity of [Mg(Valp)2Phen], inducing DNA strand breaks, as observed in the comet assay and micronucleus test. In this sense, members of the NER, HR, NHEJ and TLS repair pathways are required for the repair of DNA lesions induced by [Mg(Valp)2Phen]. Interestingly, BER proteins apparently increase the cytotoxic potential of the drug. Furthermore, the [Mg(Valp)2Phen] showed higher cytotoxicity in V79 cells and yeast when compared to sodium valproate indicating applicability as a cytotoxic agent.
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The whiteleg marine shrimp Penaeus vannamei, originally from the Eastern Pacific Ocean, now inhabits tropical waters across Asia and Central and Southern America. This benthic species exhibits rapid growth, wide salinity and temperature tolerance, and disease resistance. These physiological traits have led to extensive research on its osmoregulatory mechanisms, including next-generation sequencing, transcriptomic analyses, and lipidomic responses. In crustaceans, osmotic and ionic homeostasis is primarily maintained by the membrane-bound metalloenzyme (Na+, K+)-ATPase. However, little is known about how various ligands modulate this enzyme in P. vannamei. Here, we examined the kinetic characteristics of the gill (Na+, K+)-ATPase to get biochemical insights into its modulation. A prominent immunoreactive band of ~120 kDa, corresponding to the (Na+, K+)-ATPase alpha-subunit, was identified. The enzyme exhibited two ATP hydrolyzing sites with K0.5 = 0.0003 ± 0.00002 and 0.05 ± 0.003 mmol L-1 and was stimulated by low sodium ion concentrations. Potassium and ammonium ions also stimulated enzyme activity with similar K0.5 values of 0.08 ± 0.004 and 0.06 ± 0.003 mmol L-1, respectively. Ouabain inhibition profile suggested a single enzyme isoform with a KI value of 2.10 ± 0.16 mmol L-1. Our findings showed significant kinetic differences in the (Na+, K+)-ATPase in Penaeus vannamei compared to marine and freshwater crustaceans. We expect our results to enhance understanding of the modulation of gill (Na+, K+)-ATPase in Penaeus vannamei and to provide a valuable tool for studying the shrimp's biochemical acclimation to varying salinity conditions.
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Tropical fruit juices produced from native fruits have been widely marketed by small agribusinesses in the Brazilian semiarid region, necessitating a deeper understanding of the impact of preservation methods on quality parameters. This study aimed to prepare myrtle (Eugenia gracillima Kiaersk.) tropical juice and investigate the effects of physical preservation (90 °C for 60 s) and chemical preservation (potassium sorbate and sodium benzoate) methods. Tropical juice formulations were evaluated after preparation and every 15 days during 60 days of storage in high-density polyethylene bottles at room temperature (25 ± 2 °C). Microbiological parameters, optical microscopy, physicochemical and bioactive parameters, antioxidant capacity, and color parameters were determined. Heat-treated tropical juice showed low counts of all microbiological parameters, but optical microscopy revealed the presence of filamentous fungi after 60 days of storage. Combined use of potassium sorbate and sodium benzoate effectively prevented the development of total yeasts and molds up to 28 days of storage. Bioactive compounds in myrtle pulp contribute to storage stability, mainly total phenolics, estimated at 855.86 mg gallic acid equivalents 100 g-1. The results suggest that it is possible to harness the economic and agroindustrial potential of E. gracillima Kiaersk. fruits for the production of tropical juices, but it is recommended that other technologies be explored, such as aseptic processing or the combined use of physical and chemical methods.
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Rapid coagulation of reptile blood often hinders its use in studies in remote and difficult-to-access areas, necessitating chemical preservation. Therefore, understanding the potential effects of anticoagulants on the isotopic compositions of blood is essential to avoid issues in interpreting the results for ecological studies. In this study we aimed to verify whether the storage time of the blood tissue in anticoagulants can influence its isotopic compositions of the broad-snouted caiman (Caiman latirostris), an ectothermic top predator from eastern South America. Blood samples were obtained from ten adult females of C. latirostris from a commercial breeding facility in 2015. Samples were stored in vials containing ethylenediaminetetraacetic acid (EDTA) and sodium heparin (SH) and centrifuged after 2 and 8 h to separate red blood cells and plasma. No effect of time was found on the δ13C and δ15N of whole blood, plasma, and red blood cells in contact with the two types of anticoagulants, EDTA and SH. The findings have practical implications for researchers in this field, as they suggest that anticoagulants can be used effectively for at least eight hours under refrigeration.
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This study aimed to evaluate the impact of supplementing sodium bicarbonate or a commercial blend of buffering agents (BBA) comprising calcareous calcitic, magnesium oxide, calcareous algae, and sodium bicarbonate on the productive, behavioral and metabolic parameters of Holstein cows fed starchy diets. Over a 60-day trial period, thirty-six multiparous cows with an average milk yield of 38.84 ± 9.24 kg/day and 63.74 ± 18.63 days in milk (DIM), were randomly divided into two groups. The control group (n = 18) received a supplementation of 1.1% dry matter (DM) of sodium bicarbonate (Raudi®, Totalmix, Brazil), while the BBA group (n = 18) was administered with 0.5% DM of a blend of buffering agents (Equalizer®, Nutron/Cargill, Brazil). The mean values of ruminal pH (control 6.80 ± 0.06 and BBA 6.77 ± 0.06; P > 0.05) and volatile fatty acid (VFA) production (control: acetate 62.63 ± 1.29%, propionate 22.99 ± 1.07%, butyrate 14.30 ± 0.52%; BBA: acetate 63.07 ± 1.32%, propionate 23.47 ± 1.10%, butyrate 13.70 ± 0.57%), were similar (P > 0,05) between the two groups. The value of faecal pH was higher (P < 0.05) in the BBA group (6.25 ± 0.02) than the control group (6.12 ± 0.02). Animals treated with BBA exhibited lower (P < 0,05) dry matter intake (DMI) (24.75 ± 0.64 kg/day), higher feed efficiency (FE) (1.64 ± 0.03), and reduced feeding frequency (52.89 ± 3.73 n°/day) than the control group (DMI, 26.75 ± 0.62 kg/day; FE, 1.50 ± 0.03; feeding frequency, 66.07 ± 3.64 n°/day). Milk production remained similar across both groups (control, 39.11 ± 0.92 kg/day and BBA, 39.87 ± 0.92 kg/day; P > 0.05). Notably, the control group displayed a higher (P < 0,05) concentration of milk protein (1.21 ± 0.05 kg/day) than the BBA (1.18 ± 0.05 kg/day) group. The study concluded that both treatments effectively buffered the rumen and mitigated the risk of ruminal acidosis. Moreover, the higher faecal pH in the BBA-treated group suggests potential intestinal action attributable to the synergistic effects of diverse additives with buffering properties. Despite a reduced DMI, BBA-treated animals exhibited improved FE.
Subject(s)
Animal Feed , Diet , Lactation , Rumen , Animals , Cattle/physiology , Female , Lactation/drug effects , Diet/veterinary , Rumen/metabolism , Rumen/drug effects , Animal Feed/analysis , Dietary Supplements/analysis , Milk/chemistry , Buffers , Sodium Bicarbonate/administration & dosage , Sodium Bicarbonate/pharmacology , Fatty Acids, Volatile/metabolism , Fatty Acids, Volatile/analysis , Random Allocation , Hydrogen-Ion Concentration , Behavior, Animal/drug effects , Animal Nutritional Physiological Phenomena/drug effects , BrazilABSTRACT
This study aimed to evaluate the effects of sodium hypochlorite (NaOCl), chlorhexidine (CHX), and the glycolic extract of propolis (GEP) as endodontic irrigants and of calcium hydroxide [Ca(OH)2], CHX, or Ca(OH)2 + CHX as intracanal medications on the capacity of the lipoteichoic acid (LTA) of Enterococcus faecalis in macrophages' proinflammatory cytokines production. Freshly extracted 108 human single-rooted teeth were used in this study. The LTA of E. faecalis was standardized in double-distilled pyrogen-free water (250 µg/mL) and inoculated into the specimens subdivided into nine subgroups (n = 12). Cultures of murine macrophages (RAW 264.7) were treated with 30 µL of each sample collected from root canals and incubated (37 °C, 5% CO2) for 24 h. Lastly, anti-TNF-α, anti-IL-6, anti-IP-10, anti-MIP-1α, anti-G-CSF, and anti-IL-1ß DuoSet kits were used to perform an ELISA assay. Data were analyzed using one-way ANOVA and Tukey test (p ≥ 0.05). It was found that 1% NaOCl was the most effective irrigant in reducing the capacity of LTA in cytokines production, followed by 12% GEP and 2% CHX, respectively. Ca(OH)2 + CHX presented the best results when associated with NaOCl or GEP. Thus, NaOCl or GEP associated with Ca(OH)2 + CHX were effective in reducing the capacity of LTA in different macrophages pro-inflammatory cytokines production.
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BACKGROUND: Various types of hydrogel compounds have recently been developed for controlling invasive and pest ants in a range of environmental settings including agricultural, urban and natural areas. The current study evaluated the potential of sodium polyacrylate (ACR) hydrogels to effectively deliver liquid baits to Argentine ants. RESULTS: Relative to standard polyacrylamide (PAM) hydrogels, individual ACR hydrogel particles were approximately five-fold heavier; this may affect how ants interact with the bait particles, and further influence bait uptake and efficacy. Additionally, ACR hydrogels had significantly higher water absorption capacity and significantly slower rate of water loss, especially during the first 2 h. The efficacy of ACR hydrogel bait containing 0.005% fipronil and various attractants was evaluated on laboratory colonies. Results demonstrated that ACR hydrogel acceptance is significantly increased by the addition of feeding attractants. In addition, a field trial was performed in a nature reserve invaded by Argentine ants to evaluate the efficacy of ACR hydrogel bait. The field trial demonstrated that ACR hydrogel bait containing 0.005% fipronil with various attractants is highly effective and that ant densities throughout the baited plots declined by >99% within 7 days. CONCLUSIONS: The results of this study demonstrate that: (i) fipronil is highly effective for Argentine ant control in natural areas when used in low concentrations (0.005%); (ii) ACR hydrogels are an effective tool for delivering liquid baits to Argentine ants; and (iii) hydrogel baits augmented with various attractants including salt, protein and pheromone are highly attractive to Argentine ants. © 2024 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
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Glomerular filtration rate (GFR) impairment is common both intraoperatively and in the early postoperative period of major surgeries, even elective ones. In some patients, such impairment is subtle and short-lasting, not even detected by increases in serum creatinine (sCr) and, consequently, not of sufficient magnitude to fulfill acute kidney injury (AKI) sCr-based criteria. In patients with a GFR decrease of greater magnitude, significant increases in sCr will occur but, unfortunately, usually at a late time in its progression. Both urinary and serum biomarkers have been proposed to be capable of anticipating AKI development but they are not widely available nor cost-effective in most centers. In this context, a urine biochemical approach using urinary sodium concentration (NaU) and the fractional excretion of potassium (FeK) has been proposed, anticipating the level of renal microcirculatory stress and decreases in GFR. An educational postoperative case example is presented highlighting the relevance that this approach can have in the correct interpretation of sCr values, bringing more dynamism to renal function monitoring. How to cite this article: Maciel AT. Optimizing Postoperative Acute Kidney Injury Monitoring Using a Urine Biochemical Approach-Time to Bring More Dynamism to Serum Creatinine Evaluation! Indian J Crit Care Med 2024;28(8):729-733.
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BACKGROUND: Acute myeloid leukemia (AML) is a hematological neoplasm of rapid and progressive onset, and is the most common form of leukemia in adults. Chemoresistance to conventional treatments such as cytarabine (Ara-C) and daunorubicin is a main cause of relapse, recurrence, metastasis, and high mortality in AML patients. It is known that sodium caseinate (SC), a salt derived from casein, a milk protein, inhibits growth and induces apoptosis in acute myeloid leukemia cells but not in normal hematopoietic cells. However, it is unknown whether SC retains its antileukemic effect in cytarabine-resistant AML cell lines. OBJECTIVE: To evaluate the antineoplastic effect of SC in cytarabine-resistant leukemia models. METHODS: The SC inhibits the growth and induces apoptosis in parental WEHI-3 AML cells. Here, we generated two cytarabine-resistant sublines, WEHI-CR25 and WEHI-CR50, which exhibit 6- and 16-fold increased resistance to cytarabine, respectively, compared to the parental WEHI-3 cells. Thus, these sublines mimic a chemoresistant model. RESULTS: We demonstrate that WEHI-CR25 and WEHI-CR50 cells retain sensitivity to SC, similar to parental WEHI-3 cells. This sensitivity results in inhibited cell proliferation, induced apoptosis, and increased expression of ENT1 and dCK, molecules involved in the entry and metabolism of Ara-C, while decreasing MDR1 expression. Additionally, we observed that SC prolonged the survival of WEHI-CR50 tumor-bearing mice, despite their resistance to Ara-C. CONCLUSION: This is the first evidence that SC, a milk protein, may inhibit proliferation and induce apoptosis in cytarabine-resistant cells.
Subject(s)
Apoptosis , Caseins , Cytarabine , Drug Resistance, Neoplasm , Leukemia, Myeloid, Acute , Cytarabine/pharmacology , Animals , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/pathology , Drug Resistance, Neoplasm/drug effects , Mice , Cell Line, Tumor , Caseins/pharmacology , Apoptosis/drug effects , Cell Proliferation/drug effects , Antineoplastic Agents/pharmacologyABSTRACT
This systematic review aims to evaluate whether the application of antioxidant solutions can enhance the bond strength of resin-based materials to sodium hypochlorite (NaOCl)-treated dentin. This study follows the PICOT strategy: population (sodium hypochlorite-treated dentin), intervention (application of antioxidants), control (distilled water), outcome (bond strength), and type of studies (in vitro studies). The systematic review and meta-analysis were conducted following PRISMA guidelines. Electronic databases were searched for in vitro studies evaluating the effects of antioxidants on bond strength to sodium hypochlorite-treated dentin. Two independent reviewers screened articles, extracted data, and assessed risk of bias. Meta-analyses were performed using a random-effects model to compare standardized mean differences in bond strength between antioxidant pretreatment and control groups. Inclusion criteria consisted of in vitro studies that examined the bond strength of resin-based materials to NaOCl-treated dentin with antioxidant application, while exclusion criteria included studies with incomplete data, those not using a control group, or those that did not directly measure bond strength. From 3041 initial records, 29 studies were included in the qualitative analysis and 25 in the meta-analysis. Ascorbic acid, sodium ascorbate, grape seed extract, green tea, and rosmarinic acid significantly improved bond strength to sodium hypochlorite-treated dentin (p < 0.05). The effectiveness of grape seed extract varied with adhesive system type. Hesperidin, p-toluene sulfonic acid, and sodium thiosulfate did not significantly improve bond strength. Most studies had a high risk of bias. This suggests that the conclusions drawn from these studies should be interpreted with caution, and further research with more robust methodologies may be needed to confirm the findings. In conclusion, this systematic review implies that certain antioxidants can improve bond strength to sodium hypochlorite-treated dentin, with efficacy depending on the specific agent and adhesive system used. Further standardized studies are needed to optimize protocols and confirm these findings.
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Clinical and preclinical studies have elucidated the favorable effects of Inhibitors of Sodium-Glucose Cotransporter-2 (iSGLT2) in patients and animal models with type 2 diabetes. Notably, these inhibitors have shown significant benefits in reducing hospitalizations and mortality among patients with heart failure. However, despite their incorporation into clinical practice for indications beyond diabetes, the decision-making process regarding their use often lacks a systematic approach. The selection of iSGLT2 remains arbitrary, with only a limited number of studies simultaneously exploring the different classes of them. Currently, no unique guideline establishes their application in both clinical and basic research. This review delves into the prevalent use of iSGLT2 in animal models previously subjected to induced cardiac stress. We have compiled key findings related to cardioprotection across various animal models, encompassing diverse dosages and routes of administration. Beyond their established role in diabetes management, iSGLT2 has demonstrated utility as agents for safeguarding heart health and cardioprotection can be class-dependent among the iSGLT2. These findings may serve as valuable references for other researchers. Preclinical studies play a pivotal role in ensuring the safety of novel compounds or treatments for potential human use. By assessing side effects, toxicity, and optimal dosages, these studies offer a robust foundation for informed decisions, identifying interventions with the highest likelihood of success and minimal risk to patients. The insights gleaned from preclinical studies, which play a crucial role in highlighting areas of knowledge deficiency, can guide the exploration of novel mechanisms and strategies involving iSGLT2.
Subject(s)
Benzhydryl Compounds , Canagliflozin , Cardiotonic Agents , Glucosides , Sodium-Glucose Transporter 2 Inhibitors , Glucosides/therapeutic use , Glucosides/pharmacology , Animals , Benzhydryl Compounds/therapeutic use , Benzhydryl Compounds/pharmacology , Humans , Cardiotonic Agents/therapeutic use , Cardiotonic Agents/pharmacology , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Sodium-Glucose Transporter 2 Inhibitors/pharmacology , Canagliflozin/therapeutic use , Canagliflozin/pharmacology , Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/therapeutic use , Hypoglycemic Agents/pharmacology , Drug Evaluation, PreclinicalABSTRACT
Dietary sodium restriction increases plasma triglycerides (TG) and total cholesterol (TC) concentrations as well as causing insulin resistance and stimulation of the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system. Stimulation of the angiotensin II type-1 receptor (AT1) is associated with insulin resistance, inflammation, and the inhibition of adipogenesis. The current study investigated whether aerobic exercise training (AET) mitigates or inhibits the adverse effects of dietary sodium restriction on adiposity, inflammation, and insulin sensitivity in periepididymal adipose tissue. LDL receptor knockout mice were fed either a normal-sodium (NS; 1.27% NaCl) or a low-sodium (LS; 0.15% NaCl) diet and were either subjected to AET for 90 days or kept sedentary. Body mass, blood pressure (BP), hematocrit, plasma TC, TG, glucose and 24-hour urinary sodium (UNa) concentrations, insulin sensitivity, lipoprotein profile, histopathological analyses, and gene and protein expression were determined. The results were evaluated using two-way ANOVA. Differences were not observed in BP, hematocrit, diet consumption, and TC. The LS diet was found to enhance body mass, insulin resistance, plasma glucose, TG, LDL-C, and VLDL-TG and reduce UNa, HDL-C, and HDL-TG, showing a pro-atherogenic lipid profile. In periepididymal adipose tissue, the LS diet increased tissue mass, TG, TC, AT1 receptor, pro-inflammatory macro-phages contents, and the area of adipocytes; contrarily, the LS diet decreased anti-inflammatory macrophages, protein contents and the transcription of genes related to insulin sensitivity. The AET prevented insulin resistance, but did not protect against dyslipidemia, adipose tissue pro-inflammatory profile, increased tissue mass, AT1 receptor expression, TG, and TC induced by the LS diet.
Subject(s)
Adiposity , Diet, Sodium-Restricted , Inflammation , Insulin Resistance , Physical Conditioning, Animal , Animals , Mice , Inflammation/metabolism , Inflammation/prevention & control , Male , Mice, Knockout , Intra-Abdominal Fat/metabolism , Receptors, LDL/genetics , Receptors, LDL/metabolismABSTRACT
BACKGROUND: Sodium disturbances are observed in one-third of patients with COVID-19 and result from multifaceted mechanisms. Notably, hyponatremia is associated with disease progression and mortality. AIM: We aimed to analyze the impact of hyponatremia on COVID-19 outcomes and its correlation with clinical and laboratory parameters during the first wave. METHODS: We evaluated the sodium levels of 558 patients with COVID-19 between 21 March 2020, and 31 July 2020, at a single center. We performed linear regression analyses to explore the correlation of sodium levels with COVID-19-related outcomes, demographic data, signs and symptoms, and laboratory parameters. Next, we conducted Pearson correlation analyses. A p-value < 0.05 was considered significant. RESULTS: Hyponatremia was found in 35.3% of hospitalized patients with COVID-19. This was associated with the need for intensive care transfer (B = -1.210, p = 0.009) and invasive mechanical ventilation (B = -1.063, p = 0.032). Hyponatremia was frequently found in oncologic patients (p = 0.002) and solid organ transplant recipients (p < 0.001). Sodium was positively associated with diastolic blood pressure (p = 0.041) and productive cough (p = 0.022) and negatively associated with dry cough (p = 0.032), anorexia (p = 0.004), and nausea/vomiting (p = 0.007). Regarding the correlation of sodium levels with other laboratory parameters, we observed a positive correlation with hematocrit (p = 0.011), lymphocytes (p = 0.010), pCO2 (p < 0.0001), bicarbonate (p = 0.0001), and base excess (p = 0.008) and a negative correlation with the neutrophil-to-lymphocyte ratio (p = 0.009), the platelet-to-lymphocyte ratio (p = 0.033), and arterial blood glucose (p = 0.016). CONCLUSIONS: Hyponatremia is a risk factor for adverse outcomes in COVID-19 patients. It is associated with demographic data and clinical and laboratory parameters. Therefore, hyponatremia is an important tool for risk stratification in COVID-19 patients.
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Machine learning is playing a crucial role in optimizing material synthesis, particularly in scenarios where several parameters related to growth exhibit different and significant outcomes. An example of such complexity is the growth of atomically thin semiconductors through chemical vapor deposition (CVD), where multiple parameters can influence the thermodynamics and reaction kinetics involved in the synthesis. Herein, we performed a set of orthogonal experiments, varying the key parameters such as temperature, carries gas flux and precursor position to identify the optimal conditions for maximizing covered area and the size of rhenium disulfide (ReS2) crystals. The experimental results were used to establish correlations among the three thermodynamic variables through an artificial neural network. Contour plots were then generated to visualize the impact on the coverage and flake size of the crystals. This study demonstrates the capability of machine learning to enhance the potential of CVD-growth for the integration of 2D semiconductors like ReS2at larger scales.
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Dronedarone (DRN) is a clinically used drug to mitigate arrhythmias with multichannel block properties, including the sodium channel Nav1.5. 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 Nav1.5 sodium current (INa) and in the ex vivo heart preparation. Embryonic human kidney cells (HEK293T/17) were used to transiently express the human isoform of Nav1.5 α-subunit. Patch-Clamp technique was employed to study INa. Neurotoxin-II (ATX-II) was used to induce the late sodium current (INaLate). 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 Nav1.5 at pHe 7.0. The recovery from INa 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 INa, 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 INaLate. 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 Nav1.5 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.
Subject(s)
Anti-Arrhythmia Agents , Dronedarone , NAV1.5 Voltage-Gated Sodium Channel , Rats, Wistar , Humans , Hydrogen-Ion Concentration , Dronedarone/pharmacology , Animals , Male , HEK293 Cells , NAV1.5 Voltage-Gated Sodium Channel/metabolism , Rats , Anti-Arrhythmia Agents/pharmacology , Heart/drug effects , Heart/physiology , Electrocardiography/drug effects , Action Potentials/drug effects , Extracellular Space/metabolism , Extracellular Space/drug effectsABSTRACT
ABSTRACT The prevalence of nephrolithiasis is increasing worldwide. Despite advances in understanding the pathogenesis of lithiasis, few studies have demonstrated that specific clinical interventions reduce the recurrence of nephrolithiasis. The aim of this review is to analyze the current data and potential effects of iSGLT2 in lithogenesis and try to answer the question: Should we also "gliflozin" our patients with kidney stone disease?
RESUMO A prevalência da nefrolitíase está aumentando em todo o mundo. Apesar dos avanços na compreensão da patogênese da doença litiásica, poucos estudos demonstraram que intervenções clínicas específicas diminuem a recorrência da nefrolitíase. O objetivo desta revisão é analisar os dados atuais e efeitos potenciais dos iSGLT2 na doença litiásica e tentar responder à pergunta: devemos também "gliflozinar" os litiásicos?
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Abstract This study aimed to investigate the impact of the combination of Benzalkonium chloride (BAC) and sodium hypochloride (NaOCl) and its application after ethylenediaminetetraacetic acid (EDTA) in root canal irrigation procedures on the microhardness and mineral content of dentin. Distal roots of mandibular third molars were embedded in auto-polymerizing acrylic resin, sectioned coronally to apically resulting in fifty-four root sections. Thirty sections underwent microhardness evaluation, and twenty-four sections were randomly chosen for mineral analysis. The microhardness assessment comprised three groups: Group 1 (2.5% NaOCl), Group 2 (2.5% NaOCl with 0.084% BAC), and Group 3 (2.5% NaOCl with 0.084 BAC post-17% EDTA). Initial and post-irrigation microhardness values were measured for each group. For mineral analysis, samples were categorized into four groups: distilled water, 2.5% NaOCl, 2.5% NaOCl with 0.084% BAC, and 17% EDTA+2.5% NaOCl with 0.084% BAC. X-ray photoelectron spectroscopy immediately measured magnesium, phosphorus, and calcium mineral contents on dentin surfaces post-irrigation. Results indicated a significant reduction in root dentin microhardness for all solutions (p<0.05). However, no statistically significant difference in the percentage of reduction was observed among the groups (p>0.05). XPS analysis revealed no significant disparity in dentin surface mineral content among the groups (p>0.05). In conclusion, the addition of Benzalkonium chloride to sodium hypochloride, either alone or after EDTA, did not induce a significant alteration in dentin microhardness or mineral content. These findings contribute to a nuanced understanding of dental irrigation protocols and their effects on dentin properties during endodontic procedures.
Resumen Este estudio tuvo como objetivo investigar el impacto de la combinación de cloruro de benzalconio (BAC) e hipocloruro de sodio (NaOCl) y su aplicación después del ácido etilendiaminotetraacético (EDTA) en procedimientos de irrigación del conducto radicular sobre la microdureza y el contenido mineral de la dentina. Las raíces distales de los terceros molares mandibulares se incluyeron en resina acrílica autopolimerizable y se seccionaron de coronal a apical, lo que dió como resultado cincuenta y cuatro secciones de raíz. Treinta secciones se sometieron a una evaluación de microdureza y veinticuatro secciones fueron elegidas al azar para el análisis mineral. La evaluación de la microdureza comprendió tres grupos: Grupo 1 (2,5% NaOCl), Grupo 2 (2,5% NaOCl con 0,084% BAC) y Grupo 3 (2,5% NaOCl con 0,084 BAC post-17% EDTA). Para cada grupo se midieron los valores de microdureza inicial y post- irrigación. Para el análisis mineral, las muestras se clasificaron en cuatro grupos: agua destilada, 2,5% NaOCl, 2,5% NaOCl con 0,084% BAC y 17% EDTA+2,5% NaOCl con 0,084% BAC. La espectroscopía fotoelectrónica de rayos X midió inmediatamente el contenido de minerales de magnesio, fósforo y calcio en las superficies de la dentina después de la irrigación. Los resultados indicaron una reducción significativa en la microdureza de la dentina radicular para todas las soluciones (p<0,05). Sin embargo, no se observó diferencia estadísticamente significativa en el porcentaje de reducción entre los grupos (p>0,05). El análisis XPS no reveló ninguna disparidad significativa en el contenido mineral de la superficie de la dentina entre los grupos (p>0,05). En conclusión, la adición de cloruro de benzalconio al hipocloruro de sodio, solo o después de EDTA, no indujo una alteración significativa en la microdureza o el contenido mineral de la dentina. Estos hallazgos contribuyen a una comprensión matizada de los protocolos de irrigación dental y sus efectos sobre las propiedades de la dentina durante los procedimientos de endodoncia.
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RESUMEN Introducción . El consumo excesivo de sal (cloruro de sodio, NaCl) en la dieta conduce al desarrollo de hipertensión arterial (HTA) y daño de órgano blanco. Se sabe que los canales ClC-K1 y ClC-5 son reguladores esenciales del anión cloruro (Cl-), pero la contribución de este anión a los efectos deletéreos de la sal es aún desconocida. Objetivo . El objetivo de este trabajo fue evaluar la participación del Cl- en la respuesta inflamatoria y oxidativa renal y en el desarrollo de HTA. Material y métodos . Ratas Wistar macho se dividieron en cuatro grupos (n=8/grupo) y se alimentaron con diferentes dietas durante 3 semanas. control (grupo C); NaCl 8 % (grupo NaCl); dieta alta en Na+. citrato de sodio (Na3C6H5O7) 11,8 % (grupo Na); dieta alta en Cl-. cloruro de calcio (CaCl2) 3,80 %, cloruro de potasio (KCl) 3,06 % y cloruro de magnesio (MgCl2) 1,30 % (grupo Cl). Se determinó la presión arterial sistólica (PAS), función renal, marcadores de estrés oxidativo y de inflamación en corteza renal, y la expresion renal de los canales de cloruro ClC-K1 y ClC-5. Resultados . Se observó un aumento de la PAS, actividad de glutatión peroxidasa (GPx) y expresión renal de factor nuclear kappa B (NFkB) y receptor de angiotensina II tipo 1 (AT1R) en los grupos NaCl y Cl- (p<0,05). La producción de sustancias reactivas del ácido tiobarbitúrico (TBARS) aumentó en los grupos experimentales con respecto a C. La expresión de la proteína de Parkinson 7 (PARK7) disminuyó en el grupo Cl en comparación con C (p< 0,05). Los grupos NaCl y Cl- mostraron una mayor expresión de ClC-K1, mientras que ClC-5 se redujo en el grupo NaCl en comparación con C (p<0,05). Conclusión . El Cl- sería corresponsable, junto con el Na+, de desencadenar daño oxidativo e inflamatorio renal y aumentar la presión arterial; por ello se deduce la importancia de reducir la ingesta de ambos iones como medida preventiva no farmacológica para la prevención y control de la HTA. El rol de los canales ClC-K1 y ClC-5 como mediadores de este proceso queda aún por confirmarse.
ABSTRACT Background . Excessive consumption of salt (sodium chloride, NaCl) in the diet leads to the development of hypertension (HTN) and target organ damage. It is known that the ClC-K1 and ClC-5 channels are essential regulators of the chloride (Cl-) anion, but the contribution of this anion to salt-harmful effects remains unknown. Objective . The aim of this study was to evaluate the participation of Cl- in the renal inflammatory and oxidative response and in the development of HTN. Methods . Male Wistar rats were divided into four groups (n=8/group) and fed with different diets for 3 weeks. control (C group); NaCl 8% (NaCl group); high Na+ diet. sodium citrate (Na3C6H5O7) 11.8% (Na group); high Cl- diet. calcium chloride (CaCl2) 3.80%, potassium chloride (KCl) 3.06% and magnesium chloride (MgCl2) 1.30% (Cl group). Systolic blood pressure (SBP), renal function, oxidative stress and inflammation markers in the renal cortex, and renal expression of the chloride ClC-K1 and ClC-5 channels were assessed. Results . An increase in SBP, glutathione peroxidase (GPx) activity, and renal expression of nuclear factor kappa B (NFkB) and angiotensin II type 1 receptor (AT1R) were observed in the NaCl and Cl groups (p<0.05). The production of thiobarbituric acid reactive substances (TBARS) increased in the experimental groups compared with C. The expression of Parkinson disease protein 7 (PARK7) decreased in the Cl group compared with C (p< 0.05). The NaCl and Cl groups showed increased expression of ClC-K1, while ClC-5 was reduced in the NaCl group compared with C (p<0.05) Conclusion . Cl- would be co-responsible together with Na+ in triggering oxidative and inflammatory kidney damage and increasing blood pressure. This indicates the importance of reducing the intake of both ions as a non-pharmacological preventive measure for the prevention and control of HTN. The role of ClC-K1 and ClC-5 channels as mediators of this process remains to be confirmed.
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This study evaluated the effect of solutions containing aminomethacrylate copolymer (AA) and sodium fluoride (F; 225 ppm F-) or fluoride plus stannous chloride (FSn; 225 ppm F-, 800 ppm Sn2+) against enamel and dentin erosion/abrasion. Solutions F, FSn, AA, F+AA, FSn+AA, and deionized water as negative control were tested. Bovine enamel and dentin specimens (n = 13/solution/substrate) underwent a set of erosion-abrasion cycles (0.3% citric acid [5 min, 4×/day], human saliva [1 h, 4×/day], brushing [15 s, 2×/day], and treatments [2 min, 2×/day]) for each of five days. Initial enamel erosion was evaluated using Knoop microhardness after the first and second acid challenge on day 1, and surface loss with profilometry after day 5. KOH-soluble fluoride was assessed. Data were analyzed with ANOVA/Tukey tests. The combination of fluoride and AA resulted in higher protection against enamel erosion, whereas this was not the case for the combination of AA and FSn. All treatments protected against enamel and dentin loss. The lowest surface loss values were observed with F+AA and FSn+AA. The polymer did not significantly influence the KOH-soluble fluoride formation on enamel/dentin specimens. The aminomethacrylate copolymer effectively enhanced the efficacy of sodium fluoride against initial erosion and improved the control of enamel and dentin wear of F and FSn solutions.