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Mikrochimica Acta Jan 2024The combination of multi-walled carbon nanotubes (MWCNT) and carbon black (CB) is presented to produce a high-performance electrically conductive recycled additive...
Multi-walled carbon nanotubes/carbon black/rPLA for high-performance conductive additive manufacturing filament and the simultaneous detection of acetaminophen and phenylephrine.
The combination of multi-walled carbon nanotubes (MWCNT) and carbon black (CB) is presented to produce a high-performance electrically conductive recycled additive manufacturing filament. The filament and subsequent additively manufactured electrodes were characterised by TGA, XPS, Raman, and SEM and showed excellent low-temperature flexibility. The MWCNT/CB filament exhibited an improved electrochemical performance compared to an identical in-house produced bespoke filament using only CB. A heterogeneous electrochemical rate constant, [Formula: see text] of 1.71 (± 0.19) × 10 cm s was obtained, showing an almost six times improvement over the commonly used commercial conductive CB/PLA. The filament was successfully tested for the simultaneous determination of acetaminophen and phenylephrine, producing linear ranges of 5-60 and 5-200 μM, sensitivities of 0.05 μA μM and 0.14 μA μM, and limits of detection of 0.04 μM and 0.38 μM, respectively. A print-at-home device is presented where a removable lid comprised of rPLA can be placed onto a drinking vessel and the working, counter, and reference components made from our bespoke MWCNT/CB filament. The print-at-home device was successfully used to determine both compounds within real pharmaceutical products, with recoveries between 87 and 120% over a range of three real samples. This work paves the way for fabricating new highly conductive filaments using a combination of carbon materials with different morphologies and physicochemical properties and their application to produce additively manufactured electrodes with greatly improved electrochemical performance.
Topics: Acetaminophen; Nanotubes, Carbon; Soot; Phenylephrine; Electrochemical Techniques
PubMed: 38225436
DOI: 10.1007/s00604-023-06175-2 -
International Journal of Biological... Apr 2024Pathological cardiac hypertrophy (CH) is driven by maladaptive changes in myocardial cells in response to pressure overload or other stimuli. CH has been identified as a...
Pathological cardiac hypertrophy (CH) is driven by maladaptive changes in myocardial cells in response to pressure overload or other stimuli. CH has been identified as a significant risk factor for the development of various cardiovascular diseases, ultimately resulting in heart failure. Melanoma differentiation-associated protein 5 (MDA5), encoded by interferon-induced with helicase C domain 1 (IFIH1), is a cytoplasmic sensor that primarily functions as a detector of double-stranded ribonucleic acid (dsRNA) viruses in innate immune responses; however, its role in CH pathogenesis remains unclear. Thus, the aim of this study was to examine the relationship between MDA5 and CH using cellular and animal models generated by stimulating neonatal rat cardiomyocytes with phenylephrine and by performing transverse aortic constriction on mice, respectively. MDA5 expression was upregulated in all models. MDA5 deficiency exacerbated myocardial pachynsis, fibrosis, and inflammation in vivo, whereas its overexpression hindered CH development in vitro. In terms of the underlying molecular mechanism, MDA5 inhibited CH development by promoting apoptosis signal-regulating kinase 1 (ASK1) phosphorylation, thereby suppressing c-Jun N-terminal kinase/p38 signaling pathway activation. Rescue experiments using an ASK1 activation inhibitor confirmed that ASK1 phosphorylation was essential for MDA5-mediated cell death. Thus, MDA5 protects against CH and is a potential therapeutic target.
Topics: Mice; Rats; Animals; Interferon-Induced Helicase, IFIH1; MAP Kinase Kinase Kinase 5; Apoptosis; Cardiomegaly; Signal Transduction; JNK Mitogen-Activated Protein Kinases
PubMed: 38432272
DOI: 10.1016/j.ijbiomac.2024.130542 -
Anesthesia and Pain Medicine Apr 2024Cesarean sections are commonly performed under spinal anesthesia, which can lead to hypotension, adversely affecting maternal and fetal outcomes. Hypotension following... (Review)
Review
Cesarean sections are commonly performed under spinal anesthesia, which can lead to hypotension, adversely affecting maternal and fetal outcomes. Hypotension following spinal anesthesia is generally defined as a blood pressure of 80-90% below the baseline value. Various strategies have been implemented to reduce the incidence of spinal anesthesia-induced hypotension. The administration of vasopressors is a crucial method for preventing and treating hypotension. In the past decade, phenylephrine, a primarily alpha-adrenergic agonist, has been the preferred vasopressor for cesarean sections. Recently, norepinephrine, a potent alpha-agonist with modest beta-agonist activity, has gained popularity owing to its advantages over phenylephrine. Vasopressors can be administered via a bolus or continuous infusion. Although administering boluses alone is simpler in a clinical setting, continuous prophylactic infusion initiated immediately after spinal anesthesia is more effective in reducing the incidence of hypotension. Tailoring the infusion dose based on the patient's body weight and adjusting the rate in response to blood pressure changes, in addition to using a prophylactic or rescue bolus, helps reduce blood pressure variability during cesarean sections under spinal anesthesia until neonatal delivery.
PubMed: 38725163
DOI: 10.17085/apm.24037 -
Arquivos Brasileiros de Cardiologia Apr 2024Vascular dysfunction constitutes the etiology of many diseases, such as myocardial infarction and hypertension, with the disruption of redox homeostasis playing a role...
BACKGROUND
Vascular dysfunction constitutes the etiology of many diseases, such as myocardial infarction and hypertension, with the disruption of redox homeostasis playing a role in the imbalance of the vasomotor control mechanism. Our group previously has shown that thyroid hormones exert protective effects on the aortic tissue of infarcted rats by improving angiogenesis signaling.
OBJECTIVE
Investigate the role of triiodothyronine (T3) on vascular response, exploring its effects on isolated aortas and whether there is an involvement of vascular redox mechanisms.
METHODS
Isolated aortic rings (intact- and denuded-endothelium) precontracted with phenylephrine were incubated with T3 (10-8, 10-7, 10-6, 10-5, and 10-4 M), and tension was recorded using a force-displacement transducer coupled with an acquisition system. To assess the involvement of oxidative stress, aortic rings were preincubated with T3 and subsequently submitted to an in vitro reactive oxygen species (ROS) generation system. The level of significance adopted in the statistical analysis was 5%.
RESULTS
T3 (10-4 M) promoted vasorelaxation of phenylephrine precontracted aortic rings in both intact- and denuded-endothelium conditions. Aortic rings preincubated in the presence of T3 (10-4 M) also showed decreased vasoconstriction elicited by phenylephrine (1 µM) in intact-endothelium preparations. Moreover, T3 (10-4 M) vasorelaxation effect persisted in aortic rings preincubated with NG-nitro-L-arginine methylester (L-NAME, 10 µM), a nonspecific NO synthase (NOS) inhibitor. Finally, T3 (10-4 M) exhibited, in vitro, an antioxidant role by reducing NADPH oxidase activity and increasing SOD activity in the aorta's homogenates.
CONCLUSION
T3 exerts dependent- and independent-endothelium vasodilation effects, which may be related to its role in maintaining redox homeostasis.
Topics: Animals; Vasodilation; Male; Triiodothyronine; Rats, Wistar; Oxidation-Reduction; Reactive Oxygen Species; Oxidative Stress; Phenylephrine; Endothelium, Vascular; Rats; Reproducibility of Results; Vasoconstrictor Agents; Aorta, Thoracic; In Vitro Techniques; Vasoconstriction
PubMed: 38695407
DOI: 10.36660/abc.20230236 -
Journal of Clinical Medicine Aug 2023An intact and functionally preserved endothelial layer in the graft is crucial for myocardial perfusion and graft patency after coronary artery bypass grafting (CABG)....
BACKGROUND
An intact and functionally preserved endothelial layer in the graft is crucial for myocardial perfusion and graft patency after coronary artery bypass grafting (CABG). We hypothesized that old age is a risk factor for decreased endothelial function of bypass grafts. Thus, we investigated the impact of age in patients treated with CABG on endothelial function in saphenous vein grafts.
METHODS
We mounted the saphenous vein graft segments of CABG patients < 70 ( = 33) and ≥70 ( = 40) years of age in organ bath chambers and exposed them to potassium chloride (KCl) and phenylephrine (PE) to test the receptor-independent and -dependent contractility, followed by exposure to acetylcholine (ACh) and sodium nitroprusside (SNP) to test the endothelial-dependent and -independent relaxation.
RESULTS
The maximal contraction induced by KCl (2.3 ± 1.8 vs. 1.8 ± 2 g) was stronger in patients ≥ 70 years of age. The relative contraction induced by PE in % of KCl (167 ± 64 vs. 163 ± 59%) was similar between groups. Patients aged < 70 years showed a higher endothelial-dependent relaxation induced by acetylcholine than patients ≥ 70 years (51 ± 27 vs. 42 ± 18%). The relaxation induced by SNP was similar between both groups.
CONCLUSIONS
The endothelial function of saphenous vein bypass grafts decreases during aging. Thus, age should be considered when improving graft maintenance.
PubMed: 37685521
DOI: 10.3390/jcm12175454 -
Journal of Cataract and Refractive... Feb 2024Phenylephrine, a potent sympathomimetic, induces mydriasis via iris dilator muscle contraction. Intracameral (IC) phenylephrine has been successfully used in cataract...
Phenylephrine, a potent sympathomimetic, induces mydriasis via iris dilator muscle contraction. Intracameral (IC) phenylephrine has been successfully used in cataract surgery for initial mydriasis, maintaining mydriasis, and management of intraoperative floppy-iris syndrome. Serious systemic adverse events (mainly cardiovascular) have been described with topical phenylephrine drops, but we found very little evidence of such adverse events associated with IC phenylephrine use. However, we suspect under-reporting of such adverse events, as they may instead be ascribed to anxiety, positioning, anesthesia, etc. Optimal dosage/concentrations for IC phenylephrine use in different purposes have not been fully studied. In the absence of robust evidence, we suggest that lower but effective IC phenylephrine concentrations are used: a lower concentration (0.31%), in conjunction with an anticholinergic and lidocaine, may be used for initial mydriasis. For management of intraoperative floppy-iris syndrome, 0.31% may be effective, though a higher concentration (1% to 1.25%) may be required.
Topics: Humans; Phenylephrine; Mydriasis; Mydriatics; Phacoemulsification; Iris Diseases; Iris; Intraoperative Complications; Iatrogenic Disease; Pupil
PubMed: 37748029
DOI: 10.1097/j.jcrs.0000000000001319 -
Indian Journal of Anaesthesia Apr 2024There is limited data on the effects of norepinephrine on neonatal outcomes and maternal complications relative to other vasopressors. The study aimed to compare...
Comparison of the effect of intravenous phenylephrine and norepinephrine boluses for post-spinal hypotension on neonatal outcome in elective caesarean section: A randomised controlled trial.
BACKGROUND AND AIMS
There is limited data on the effects of norepinephrine on neonatal outcomes and maternal complications relative to other vasopressors. The study aimed to compare neonatal outcomes and maternal complications after bolus intravenous doses of phenylephrine and norepinephrine for post-spinal hypotension in elective caesarean section women.
METHODS
This randomised study was done on 100 elective caesarean section women under spinal anaesthesia. Block randomisation divided women into two groups to receive intravenous phenylephrine 50 μg bolus (Group A) or norepinephrine 5 μg bolus (Group B) following post-spinal hypotension. Groups were evaluated and compared for umbilical arterial blood gas analysis, birth weight, APGAR (appearance, pulse, grimace, activity, and respiration) score, maternal haemodynamics, and complications. Kolmogorov-Smirnov and Shapiro-Wilk tests were used to verify data normality. Independent samples -test or Mann-Whitney U test was employed to compare continuous variables based on data normality, and the Chi-square test was used to determine categorical variable associations.
RESULTS
Demographic characteristics of women were found to be comparable between groups. Umbilical arterial potential of hydrogen, partial pressure of oxygen, partial pressure of carbon dioxide, base excess, bicarbonate, birth weight, and APGAR scores were comparable across groups, showing no significant differences ( > 0.05). Groups had similar maternal haemodynamic characteristics and episodes of nausea, vomiting, and chest pain across groups without statistical significance ( > 0.05).
CONCLUSION
No notable distinction was found between neonatal outcomes and maternal complications between phenylephrine and norepinephrine bolus regimens. Norepinephrine can be used as an alternative to phenylephrine post-spinal hypotension in women undergoing elective caesarean section.
PubMed: 38586272
DOI: 10.4103/ija.ija_920_23 -
Hospital Pharmacy Feb 2024This case summarizes a 66 year old woman with a past medical history of asthma, breast cancer, anxiety, and chronic back pain with prior surgical insertion of spinal...
This case summarizes a 66 year old woman with a past medical history of asthma, breast cancer, anxiety, and chronic back pain with prior surgical insertion of spinal hardware, presenting for removal of spinal hardware at L5-S1 and spinal laminectomy and fusion at L4-L5. Her course was complicated by acute blood loss anemia and post-operative hypotension managed with a phenylephrine infusion, for which she experienced a possible anaphylactic reaction requiring upgrade to the intensive care unit. She was managed using intramuscular epinephrine, diphenhydramine, methylprednisolone, albuterol, famotidine, and oxygen. As phenylephrine is structurally similar to the endogenous catecholamines epinephrine and norepinephrine, diagnosis of her reaction was difficult. However, phenylephrine contains sodium metabisulfite, a preservative sulfite that may cause allergic-type reactions, particularly in patients with asthma in their medical history. Her hypersensitivity reaction was likely secondary to her use of phenylephrine, and she was discharged with a plan for outpatient follow up with the allergy team. As this case exemplifies, patients with a predisposition to allergic reactions should be closely monitored for possible hypersensitivity to preservatives and excipients in medications.
PubMed: 38223868
DOI: 10.1177/00185787231185867 -
Cureus Jul 2023Background Maternal hypotension occurs in up to 80% of parturients during cesarean section (CS) under spinal anesthesia. Phenylephrine, a direct-acting α-1 agonist, has...
A Prospective Single-Center Brazilian Study Investigating the Efficacy and Safety of Prophylactic Phenylephrine Infusion for the Management of Hypotension During Cesarean Section Under Spinal Anesthesia.
Background Maternal hypotension occurs in up to 80% of parturients during cesarean section (CS) under spinal anesthesia. Phenylephrine, a direct-acting α-1 agonist, has been widely recommended for the prevention of hypotension. We evaluated the efficacy and safety of phenylephrine infusion to prevent hypotension in obese and non-obese patients during cesarean section. Methods One hundred forty-one patients were included in this single-arm study. Patients received prophylactic phenylephrine infusion at a rate of 50 μg/min immediately after spinal local anesthetic injection until delivery. Hypotension was defined as a systolic blood pressure <100 mmHg or <20% of baseline. The primary outcome was the incidence of hypotension. Results The incidence of hypotension was 17%. The median and interquartile range (IQR) of the number of hypotensive episodes was 0 (0-0). It was observed that 79.1% of the patients had hypotension in the first six minutes. Reactive hypertension and bradycardia occurred in 20.5 and 12.7% of the patients, respectively. In addition, there was a higher incidence of bradycardia in pregnant women with a body index mass of < 30 kg/m. Patients with baseline systolic blood pressure <120 mmHg had a threefold increased risk of hypotension. The incidence of nausea and vomiting was 13.4 and 2.8%, respectively. The incidence of an Apgar score <7 at the first minute was 2.8%, and no neonates presented an Apgar score <7 at the fifth minute. A pH of <7.2 occurred in 6.3% of the neonates. All neonates had no sequelae and were discharged together with their mothers. Conclusion The prophylactic infusion of phenylephrine 50 μg/min is safe and demonstrates efficacy in reducing maternal hypotension providing adequate maternal hemodynamic stability during CS under spinal anesthesia.
PubMed: 37602045
DOI: 10.7759/cureus.42156 -
Biomedicine & Pharmacotherapy =... May 2024SGLT2i reduce cardiac hypertrophy, but underlying mechanisms remain unknown. Here we explore a role for serine/threonine kinases (STK) and sodium hydrogen exchanger...
BACKGROUND
SGLT2i reduce cardiac hypertrophy, but underlying mechanisms remain unknown. Here we explore a role for serine/threonine kinases (STK) and sodium hydrogen exchanger 1(NHE1) activities in SGLT2i effects on cardiac hypertrophy.
METHODS
Isolated hearts from db/db mice were perfused with 1 µM EMPA, and STK phosphorylation sites were examined using unbiased multiplex analysis to detect the most affected STKs by EMPA. Subsequently, hypertrophy was induced in H9c2 cells with 50 µM phenylephrine (PE), and the role of the most affected STK (p90 ribosomal S6 kinase (RSK)) and NHE1 activity in hypertrophy and the protection by EMPA was evaluated.
RESULTS
In db/db mice hearts, EMPA most markedly reduced STK phosphorylation sites regulated by RSKL1, a member of the RSK family, and by Aurora A and B kinases. GO and KEGG analysis suggested that EMPA inhibits hypertrophy, cell cycle, cell senescence and FOXO pathways, illustrating inhibition of growth pathways. EMPA prevented PE-induced hypertrophy as evaluated by BNP and cell surface area in H9c2 cells. EMPA blocked PE-induced activation of NHE1. The specific NHE1 inhibitor Cariporide also prevented PE-induced hypertrophy without added effect of EMPA. EMPA blocked PE-induced RSK phosphorylation. The RSK inhibitor BIX02565 also suppressed PE-induced hypertrophy without added effect of EMPA. Cariporide mimicked EMPA's effects on PE-treated RSK phosphorylation. BIX02565 decreased PE-induced NHE1 activity, with no further decrease by EMPA.
CONCLUSIONS
RSK inhibition by EMPA appears as a novel direct cardiac target of SGLT2i. Direct cardiac effects of EMPA exert their anti-hypertrophic effect through NHE-inhibition and subsequent RSK pathway inhibition.
Topics: Animals; Sodium-Hydrogen Exchanger 1; Glucosides; Cardiomegaly; Mice; Phosphorylation; Ribosomal Protein S6 Kinases, 90-kDa; Male; Benzhydryl Compounds; Sodium-Glucose Transporter 2 Inhibitors; Cell Line; Rats; Myocytes, Cardiac; Mice, Inbred C57BL; Signal Transduction
PubMed: 38522235
DOI: 10.1016/j.biopha.2024.116477