-
Physiological Reports Jul 2024To better understand mechanisms of serotonin- (5-HT) mediated vasorelaxation, isolated lateral saphenous veins from cattle were assessed for vasoactivity using myography...
To better understand mechanisms of serotonin- (5-HT) mediated vasorelaxation, isolated lateral saphenous veins from cattle were assessed for vasoactivity using myography in response to increasing concentrations of 5-HT or selective 5-HT receptor agonists. Vessels were pre-contracted with 1 × 10 M phenylephrine and exposed to increasing concentrations of 5-HT or 5-HT receptor agonists that were selective for 5-HT, 5-HT, 5-HT, and 5-HT. Vasoactive response data were normalized as a percentage of the maximum contractile response induced by the phenylephrine pre-contraction. At 1 × 10 M 5-HT, a relaxation was observed with an 88.7% decrease (p < 0.01) from the phenylephrine maximum. At 1 × 10 M 5-HT, a contraction was observed with a 165% increase (p < 0.01) from the phenylephrine maximum. Increasing concentrations of agonists selective for 5-HT, 5-HT, or 5-HT resulted in a 27%, 92%, or 44% (p < 0.01) decrease from the phenylephrine maximum, respectively. Of these 5-HT receptor agonists, the selective 5-HT receptor agonist resulted in the greatest potency (-log EC) value (6.30) compared with 5-HT and 5-HT receptor agonists (4.21 and 4.66, respectively). To confirm the involvement of 5-HT in 5-HT-mediated vasorelaxation, blood vessels were exposed to either DMSO (solvent control) or a selective 5-HT antagonist (1 × 10 M) for 5-min prior to the phenylephrine pre-contraction and 5-HT additions. Antagonism of the 5-HT receptor attenuated the vasorelaxation caused by 5-HT. Approximately 94% of the vasorelaxation occurring in response to 5-HT could be accounted for through 5-HT, providing strong evidence that 5-HT-mediated vasorelaxation occurs through 5-HT activation in bovine peripheral vasculature.
Topics: Animals; Cattle; Vasodilation; Saphenous Vein; Serotonin; Receptors, Serotonin; Receptors, Serotonin, 5-HT4; Phenylephrine; Serotonin Receptor Agonists; Male
PubMed: 38946059
DOI: 10.14814/phy2.16128 -
Medicine May 2024This study was aimed to analyze ocular biometric changes following cycloplegia in pediatric patients with strabismus and amblyopia. Cycloplegia is routinely used to... (Observational Study)
Observational Study
This study was aimed to analyze ocular biometric changes following cycloplegia in pediatric patients with strabismus and amblyopia. Cycloplegia is routinely used to measure refractive error accurately by paralyzing accommodation. However, effects on axial length (AL), anterior chamber depth (ACD), keratometry (Km), and white-to-white distance (WTW) are not well studied in this population. This retrospective study examined 797 patients (1566 eyes) undergoing cycloplegic refraction at a Samsung Kangbuk hospital pediatric ophthalmology clinic from 2010 to 2023. Ocular biometry was measured before and after instilling 1% cyclopentolate and 0.5% phenylephrine/0.5% tropicamide. Patients were categorized by strabismus diagnosis, age, refractive error and amblyopia status. Differences in AL, ACD, Km, WTW, and refractive error pre- and post-cycloplegia were analyzed using paired t tests. ACD (3.44 ± 0.33 vs 3.58 ± 0.29 mm, P < .05) and WTW (12.09 ± 0.42 vs 12.30 ± 0.60 mm, P < .05) increased significantly after cycloplegia in all groups except other strabismus subgroup (Cs) in both parameters and youngest subgroup (G1) in ACD. Refractive error demonstrated a hyperopic shift from -0.48 ± 3.00 D to -0.06 ± 3.32 D (P < .05) in overall and a myopic shift from -6.97 ± 4.27 to -8.10 ± 2.26 in high myopia (HM). Also, AL and Km did not change significantly. In conclusion, cycloplegia impacts ocular biometrics in children with strabismus and amblyopia, significantly increasing ACD and WTW. Refractive error shifts hyperopically in esotropia subgroup (ET) and myopically in high myopia subgroup (HM), eldest subgroup (G3) relating more to anterior segment changes than AL/Km. Understanding cycloplegic effects on biometry is important for optimizing refractive correction in these patients.
Topics: Humans; Amblyopia; Strabismus; Retrospective Studies; Male; Female; Child; Biometry; Mydriatics; Child, Preschool; Refraction, Ocular; Cyclopentolate; Refractive Errors; Adolescent; Anterior Chamber; Axial Length, Eye
PubMed: 38758890
DOI: 10.1097/MD.0000000000038143 -
PloS One 2023Apart from cardiotoxicity, the chemotherapeutic agent doxorubicin (DOX) provokes acute and long-term vascular toxicity. Dexrazoxane (DEXRA) is an effective drug for...
Apart from cardiotoxicity, the chemotherapeutic agent doxorubicin (DOX) provokes acute and long-term vascular toxicity. Dexrazoxane (DEXRA) is an effective drug for treatment of DOX-induced cardiotoxicity, yet it remains currently unknown whether DEXRA prevents vascular toxicity associated with DOX. Accordingly, the present study aimed to evaluate the protective potential of DEXRA against DOX-related vascular toxicity in a previously-established in vivo and ex vivo model of vascular dysfunction induced by 16 hour (h) DOX exposure. Vascular function was evaluated in the thoracic aorta in organ baths, 16h after administration of DOX (4 mg/kg) or DOX with DEXRA (40 mg/kg) to male C57BL6/J mice. In parallel, vascular reactivity was evaluated after ex vivo incubation (16h) of murine aortic segments with DOX (1 μM) or DOX with DEXRA (10 μM). In both in vivo and ex vivo experiments, DOX impaired acetylcholine-stimulated endothelium-dependent vasodilation. In the ex vivo setting, DOX additionally attenuated phenylephrine-elicited vascular smooth muscle cell (VSMC) contraction. Importantly, DEXRA failed to prevent DOX-induced endothelial dysfunction and hypocontraction. Furthermore, RT-qPCR and Western blotting showed that DOX decreased the protein levels of topoisomerase-IIβ (TOP-IIβ), a key target of DEXRA, in the heart, but not in the aorta. Additionally, the effect of N-acetylcysteine (NAC, 10 μM), a reactive oxygen species (ROS) scavenger, was evaluated ex vivo. NAC did not prevent DOX-induced impairment of acetylcholine-stimulated vasodilation. In conclusion, our results show that DEXRA fails to prevent vascular toxicity resulting from 16h DOX treatment. This may relate to DOX provoking vascular toxicity in a ROS- and TOP-IIβ-independent way, at least in the evaluated acute setting. However, it is important to mention that these findings only apply to the acute (16h) treatment period, and further research is warranted to delineate the therapeutic potential of DEXRA against vascular toxicity associated with longer-term repetitive DOX dosing.
Topics: Mice; Animals; Male; Dexrazoxane; Reactive Oxygen Species; Cardiotoxicity; Acetylcholine; Doxorubicin; Mice, Inbred C57BL; Myocytes, Cardiac; Antibiotics, Antineoplastic
PubMed: 38015959
DOI: 10.1371/journal.pone.0294848 -
Journal of Clinical Anesthesia Jun 2024Spinal anesthesia often causes hypotension, with consequent risk to the fetus. The use of vasopressor agents has been highly recommended for the prevention of spinal...
Norepinephrine or phenylephrine for the prevention of post-spinal hypotension after caesarean section: A double-blinded, randomized, controlled study of fetal heart rate and fetal cardiac output.
STUDY OBJECTIVE
Spinal anesthesia often causes hypotension, with consequent risk to the fetus. The use of vasopressor agents has been highly recommended for the prevention of spinal anesthesia-induced hypotension during caesarean delivery. Many studies have shown that norepinephrine can provide more stable maternal hemodynamics than phenylephrine. We therefore tested the hypothesis that norepinephrine preserves fetal circulation better than phenylephrine when used to treat maternal hypotension consequent to spinal anesthesia.
DESIGN
Prospective, randomized, double-blinded study.
SETTING
Operating room.
PATIENTS
We recruited 223 parturients with uncomplicated singleton pregnancies who were scheduled for elective caesarean section under combined spinal-epidural anesthesia.
INTERVENTIONS
The patients received prophylactic intravenous infusion of either 0.08 μg/kg/min norepinephrine or 0.5 μg/kg/min phenylephrine for prevention of spinal anesthesia-induced hypotension.
MEASUREMENTS
Changes in fetal heart rate and fetal cardiac output before and after spinal anesthesia were measured using noninvasive Doppler ultrasound.
MAIN RESULTS
90 subjects who received norepinephrine infusion and 93 subjects who received phenylephrine infusion were ultimately analyzed in the present study. The effects of norepinephrine and phenylephrine on the change of fetal heart rate and fetal cardiac output at 3 and 6 min after spinal block were similar. Although there was a statistically significant decrease in fetal cardiac output at 6 min after subarachnoid block initiation in both the norepinephrine group (mean difference 0.02 L/min; 95% CI, 0-0.04 L/min; P = 0.03) and the phenylephrine group (mean difference 0.02 L/min; 95% CI, 0-0.04 L/min; P = 0.02), it remained within the normal range.
CONCLUSIONS
Prophylactic infusion of comparable doses of phenylephrine or norepinephrine has similar effects on fetal heart rate and cardiac output changes after spinal anesthesia. Neither phenylephrine nor norepinephrine has meaningful detrimental effects on fetal circulation or neonatal outcomes.
PubMed: 38880002
DOI: 10.1016/j.jclinane.2024.111533 -
JA Clinical Reports Oct 2023This study compared the effects of remimazolam and sevoflurane on intraoperative hemodynamics including intraoperative hypotension (IOH).
BACKGROUND
This study compared the effects of remimazolam and sevoflurane on intraoperative hemodynamics including intraoperative hypotension (IOH).
RESULTS
This study involved adult patients undergoing noncardiac surgery using remimazolam (Group R) or sevoflurane (Group S) for maintenance anesthesia, and invasive arterial pressure measurements, from September 2020 to March 2023 at our hospital. IOH was defined as a mean blood pressure < 65 mmHg occurring for a cumulative duration of at least 10 min. A 1:1 propensity score-matching method was used. The primary endpoint was the occurrence of IOH, and the secondary endpoints were the cumulative hypotensive time, incidence of vasopressor use, and dose of vasopressor used (ephedrine, phenylephrine, dopamine, and noradrenaline). Group R comprised 169 patients, Group S comprised 393 patients, and a matched cohort of 141 patients was created by propensity score matching. There was no significant difference in the incidence of IOH between the two groups (85.1% in Group R vs. 91.5% in Group S, p = 0.138). Patients in Group R had a significantly lower cumulative hypotension duration (55 [18-119] vs. 83 [39-144] min, p = 0.005), vasopressor use (81.6% vs. 91.5%, p = 0.023), and dose of ephedrine (4 [0-8] vs. 12 [4-20] mg, p < 0.001) than those in Group S. There were no significant differences in the doses of other vasopressors between groups.
CONCLUSIONS
Compared with sevoflurane, the maintenance of anesthesia with remimazolam was not associated with a decreased incidence of IOH; however, it reduced the cumulative hypotension time, incidence of vasopressor use, and dose of ephedrine.
PubMed: 37880547
DOI: 10.1186/s40981-023-00661-5 -
BMC Chemistry Oct 2023The presence of minor components represents a challenging problem in spectrophotometric analysis of pharmaceuticals. If one component has a low absorptivity or present...
Continuous wavelet transform for solving the problem of minor components in quantitation of pharmaceuticals: a case study on the mixture of ibuprofen and phenylephrine with its degradation products.
The presence of minor components represents a challenging problem in spectrophotometric analysis of pharmaceuticals. If one component has a low absorptivity or present in a low concentration compared to the other components, this will hinder its quantitation by spectrophotometric methods. Continuous Wavelet Transform (CWT) as a signal processing technique was utilized to figure out a solution to such a problem. A comparative study was established between traditional derivative spectrophotometry (Numerical Differentiation, ND) and CWT to indicate the advantages and limitations of each technique and possibility of solving the problem of minor components. A mixture of ibuprofen (IBU) and phenylephrine (PHE) with its degradation products forming a ternary mixture was used for comparing the two techniques. The two techniques were applied on raw spectral data and on ratio spectra data resulting in four methods, namely ND, CWT, Derivative Ratio-Zero Crossing (DRZC) and Continuous Wavelet Transform Ratio-Zero Crossing (CWTR-ZC) methods. By comparing the results in laboratory prepared mixtures, CWT technique showed advantages in analysis of mixtures with minor components than ND. The proposed methods were validated according to the ICH guideline Q2(R1), where their linearity was established with correlation coefficient ranging from 0.9995 to 0.9999. The linearity was in the range 3-40 μg/mL for PHE in all methods, while for IBU it was 20-180 and 30-180 μg/mL in CWT and ND methods, respectively. The CWT methods were applied for quantitative determination of the drugs in their dosage form showing the ability of the methods to quantitate minor components in pharmaceutical formulations.
PubMed: 37876002
DOI: 10.1186/s13065-023-01059-1 -
Microvascular Research Jun 2024Patients with Takotsubo syndrome displayed endothelial dysfunction, but underlying mechanisms have not been fully clarified. This study aimed to explore molecular...
Patients with Takotsubo syndrome displayed endothelial dysfunction, but underlying mechanisms have not been fully clarified. This study aimed to explore molecular signalling responsible for catecholamine excess induced endothelial dysfunction. Human cardiac microvascular endothelial cells were challenged by epinephrine to mimic catecholamine excess. Patch clamp, FACS, ELISA, PCR, and immunostaining were employed for the study. Epinephrine (Epi) enhanced small conductance calcium-activated potassium channel current (I) through activating α1 adrenoceptor. Phenylephrine enhanced edothelin-1 (ET-1) and reactive oxygen species (ROS) production, and the effects involved contribution of I. HO enhanced I and ET-1 production. Enhancing I caused a hyperpolarization, which increases ROS and ET-1 production. BAPTA partially reduced phenylephrine-induced enhancement of ET-1 and ROS, suggesting that α1 receptor activation can enhance ROS/ET-1 generation in both calcium-dependent and calcium-independent ways. The study demonstrates that high concentration catecholamine can activate SK1-3 channels through α1 receptor-ROS signalling and increase ET-1 production, facilitating vasoconstriction.
PubMed: 38901735
DOI: 10.1016/j.mvr.2024.104699 -
Cell Death & Disease Jun 2024Pathological cardiac hypertrophy is one of the major risk factors of heart failure and other cardiovascular diseases. However, the mechanisms underlying pathological...
Pathological cardiac hypertrophy is one of the major risk factors of heart failure and other cardiovascular diseases. However, the mechanisms underlying pathological cardiac hypertrophy remain largely unknown. Here, we identified the first evidence that TNFAIP3 interacting protein 3 (TNIP3) was a negative regulator of pathological cardiac hypertrophy. We observed a significant upregulation of TNIP3 in mouse hearts subjected to transverse aortic constriction (TAC) surgery and in primary neonatal rat cardiomyocytes stimulated by phenylephrine (PE). In Tnip3-deficient mice, cardiac hypertrophy was aggravated after TAC surgery. Conversely, cardiac-specific Tnip3 transgenic (TG) mice showed a notable reversal of the same phenotype. Accordingly, TNIP3 alleviated PE-induced cardiomyocyte enlargement in vitro. Mechanistically, RNA-sequencing and interactome analysis were combined to identify the signal transducer and activator of transcription 1 (STAT1) as a potential target to clarify the molecular mechanism of TNIP3 in pathological cardiac hypertrophy. Via immunoprecipitation and Glutathione S-transferase assay, we found that TNIP3 could interact with STAT1 directly and suppress its degradation by suppressing K48-type ubiquitination in response to hypertrophic stimulation. Remarkably, preservation effect of TNIP3 on cardiac hypertrophy was blocked by STAT1 inhibitor Fludaradbine or STAT1 knockdown. Our study found that TNIP3 serves as a novel suppressor of pathological cardiac hypertrophy by promoting STAT1 stability, which suggests that TNIP3 could be a promising therapeutic target of pathological cardiac hypertrophy and heart failure.
Topics: Animals; Cardiomegaly; STAT1 Transcription Factor; Myocytes, Cardiac; Mice; Rats; Male; Mice, Inbred C57BL; Ubiquitination; Membrane Proteins; Mice, Transgenic; Humans; Phenylephrine; Protein Stability; Mice, Knockout
PubMed: 38926347
DOI: 10.1038/s41419-024-06805-4 -
Cureus Jan 2024Nasal decongestants, like phenylephrine and pseudoephedrine, are commonly used to relieve nasal obstruction in conditions such as allergic rhinitis. They induce nasal...
Utilization Pattern and Related Knowledge of Nasal Decongestants Among the General Population in Al-Qunfudah Governorate, Saudi Arabia: A Community-Based Cross-Sectional Study.
BACKGROUND
Nasal decongestants, like phenylephrine and pseudoephedrine, are commonly used to relieve nasal obstruction in conditions such as allergic rhinitis. They induce nasal passage dilation through vasoconstriction but can lead to serious side effects like hypertension and rebound congestion. Despite being easily accessible over the counter, their usage patterns and awareness of side effects are not well studied.
OBJECTIVES
The study aimed to assess the utilization pattern and public knowledge of nasal decongestants in Al-Qunfudah governorate, Saudi Arabia, in 2023.
METHODS
This observational cross-sectional study assessed the utilization pattern of nasal decongestants among those who were 10 years of age and older and resided in Al-Qunfudah governorate and its villages. Data were collected in three months, from June to August 2023, using a self-administered survey that was disseminated among the general population at Al-Qunfudah governorate on different electronic platforms like Twitter (X Corp., San Francisco, CA, United States) and Snapchat (Snap Inc., Santa Monica, CA, United States). RStudio (version 4.3.0) was used for the statistical analysis. The knowledge score showed a non-normal distribution (Shapiro-Wilk test p value < 0.001). For normally distributed qualitative variables, the factors related to nasal decongestant use were assessed using Pearson's Chi-squared test. Fisher's exact test was applied when more than 20% of cells had frequencies less than 5. A generalized linear regression model was used to assess the independent predictors of higher knowledge scores. A p-value < 0.05 indicated statistical significance.
RESULTS
Based on 410 responses, nearly 77% (n = 314) of the participants have ever used nasal decongestants. A total of 118 out of 314 (37.6%) used these medications twice daily for less than five days (81.2%, n = 255). A total of 192 (61.1%) participants used nasal decongestants based on physicians' prescriptions. Few respondents (12.9%, n = 53) and (33.2%, n = 136) correctly identified nasal mucosal ulceration and nasal dryness as adverse effects of prolonged nasal decongestants' use. However, 84.6% (n = 347) ignored their contraindications, and 55.1% (n = 226) had no idea about rebound congestion. Overall, participants displayed a moderate level of knowledge regarding nasal decongestants, with a median knowledge score of 5.0. Being a student (beta = 1.12, 95%CI, 0.19 to 2.05, p = 0.019) and being a female were independently associated with better knowledge scores (beta = 0.97, 95%CI, 0.40 to 1.54, p < 0.001). Those who ever used nasal decongestants (beta = 0.71, 95% CI: 0.07 to 1.34, p = 0.030) and those who used them three times a day (beta = 1.05, 95% CI: 0.11 to 1.99, p = 0.029) had higher knowledge scores.
CONCLUSION
More than two-thirds (76.6%) of the Al-Qunfudah general population in Saudi Arabia utilized nasal decongestants. The utilization pattern of nasal decongestants highlighted short-term usage for nasal obstruction. Despite the moderate level of knowledge of the general population about nasal decongestants, many gaps were noted regarding their systemic contraindications, side effects, and the risks of rebound congestion. A focus group discussion is advised to get a full and deep perception of the public regarding this common type of medication. Health education programs are recommended regarding this category of medications, warning them about ineffective self-medication.
PubMed: 38406038
DOI: 10.7759/cureus.53006 -
Cells Sep 2023In arteries and arterioles, a chronic increase in blood pressure raises wall tension. This continuous biomechanical strain causes a change in gene expression in vascular...
In arteries and arterioles, a chronic increase in blood pressure raises wall tension. This continuous biomechanical strain causes a change in gene expression in vascular smooth muscle cells (VSMCs) that may lead to pathological changes. Here we have characterised the functional properties of lipoma-preferred partner (LPP), a Lin11-Isl1-Mec3 (LIM)-domain protein, which is most closely related to the mechanotransducer zyxin but selectively expressed by smooth muscle cells, including VSMCs in adult mice. VSMCs isolated from the aorta of LPP knockout (LPP-KO) mice displayed a higher rate of proliferation than their wildtype (WT) counterparts, and when cultured as three-dimensional spheroids, they revealed a higher expression of the proliferation marker Ki 67 and showed greater invasion into a collagen gel. Accordingly, the gelatinase activity was increased in LPP-KO but not WT spheroids. The LPP-KO spheroids adhering to the collagen gel responded with decreased contraction to potassium chloride. The relaxation response to caffeine and norepinephrine was also smaller in the LPP-KO spheroids than in their WT counterparts. The overexpression of zyxin in LPP-KO VSMCs resulted in a reversal to a more quiescent differentiated phenotype. In native VSMCs, i.e., in isolated perfused segments of the mesenteric artery (MA), the contractile responses of LPP-KO segments to potassium chloride, phenylephrine or endothelin-1 did not vary from those in isolated perfused WT segments. In contrast, the myogenic response of LPP-KO MA segments was significantly attenuated while zyxin-deficient MA segments displayed a normal myogenic response. We propose that LPP, which we found to be expressed solely in the medial layer of different arteries from adult mice, may play an important role in controlling the quiescent contractile phenotype of VSMCs.
Topics: Mice; Animals; Zyxin; Muscle, Smooth, Vascular; Potassium Chloride; Collagen; Transcription Factors; Myocytes, Smooth Muscle; Lipoma
PubMed: 37759537
DOI: 10.3390/cells12182315