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BMC Chemistry Mar 2023Enantioseparation of five β-adrenergic blockers was studied using two mobile phases on a cellulose tris(3-chloro-4-methylphenylcarbamate) (Lux-Cellulose-2) chiral...
Enantioseparation of five β-adrenergic blockers was studied using two mobile phases on a cellulose tris(3-chloro-4-methylphenylcarbamate) (Lux-Cellulose-2) chiral column in normal phase mode. The first mobile phase composed of n-hexane: ethanol: diethylamine 60: 40: 0.1 by volume has successfully resolved the chromatographic peaks of three pairs of β-adrenergic blockers namely, bisoprolol, carvedilol and atenolol. A mixture of n-hexane: ethanol: diethyl amine 75: 25: 0.1 by volume was used as the second mobile phase to separate the four pairs of enantiomers, metoprolol, carvedilol, nebivolol and atenolol with high resolution values. The mobile phases were pumped at a flow rate 1 mL/min with column temperature 25 °C using a UV detector at 230 nm. Molecular docking simulations of the five pairs of enantiomers was carried out in the cavities of the chiral stationary phase to gain a better understanding of the interaction between analyte enantiomers and chiral stationary phase and to better understand the mechanism of chiral recognition. According to the results, hydrogen bond interactions and π-π- interactions were the main types of interaction involved in the chiral recognition. Molecular dynamics simulation was performed to investigate the solvent effect on the interaction of the five pair of enantiomers in the chiral stationary phase cavity under dynamic conditions.
PubMed: 36927568
DOI: 10.1186/s13065-023-00925-2 -
International Journal of Environmental... Feb 2023Sympathetic stress stimulates norepinephrine (NE) release from sympathetic nerves. During pregnancy, it modifies the fetal environment, increases NE to the fetus through...
BACKGROUND
Sympathetic stress stimulates norepinephrine (NE) release from sympathetic nerves. During pregnancy, it modifies the fetal environment, increases NE to the fetus through the placental NE transporter, and affects adult physiological functions. Gestating rats were exposed to stress, and then the heart function and sensitivity to in vivo adrenergic stimulation were studied in male progeny.
METHODS
Pregnant Sprague-Dawley rats were exposed to cold stress (4 °C/3 h/day); rats' male progeny were euthanized at 20 and 60 days old, and their hearts were used to determine the β-adrenergic receptor (βAR) (radioligand binding) and NE concentration. The in vivo arterial pressure response to isoproterenol (ISO, 1 mg/kg weight/day/10 days) was monitored in real time (microchip in the descending aorta).
RESULTS
Stressed male progeny presented no differences in ventricular weight, the cardiac NE was lower, and high corticosterone plasma levels were recorded at 20 and 60 days old. The relative abundance of β1 adrenergic receptors decreased by 36% and 45%, respectively ( < 0.01), determined by Western blot analysis without changes in β2 adrenergic receptors. A decrease in the ratio between β1/β2 receptors was found. Displacement of H-dihydroalprenolol (DHA) from a membrane fraction with propranolol (β antagonist), atenolol (β1 antagonist), or zinterol (β2 agonist) shows decreased affinity but no changes in the β-adrenergic receptor number. In vivo exposure to ISO to induce a β-adrenergic overload provoked death in 50% of stressed males by day 3 of ISO treatment.
CONCLUSION
These data suggest permanent changes to the heart's adrenergic response after rat progeny were stressed in the uterus.
Topics: Rats; Female; Male; Pregnancy; Animals; Humans; Rats, Sprague-Dawley; Mothers; Placenta; Norepinephrine; Receptors, Adrenergic, beta; Adrenergic Agents
PubMed: 36901294
DOI: 10.3390/ijerph20054285 -
Scientific Reports Mar 2023Midlife hypertension is an important risk factor for cognitive impairment and dementia, including Alzheimer's disease. We investigated the effects of long-term treatment...
Midlife hypertension is an important risk factor for cognitive impairment and dementia, including Alzheimer's disease. We investigated the effects of long-term treatment with two classes of antihypertensive drugs to determine whether diverging mechanisms of blood pressure lowering impact the brain differently. Spontaneously hypertensive rats (SHR) were either left untreated or treated with a calcium channel blocker (amlodipine) or beta blocker (atenolol) until one year of age. The normotensive Wistar Kyoto rat (WKY) was used as a reference group. Both drugs lowered blood pressure equally, while only atenolol decreased heart rate. Cerebrovascular resistance was increased in SHR, which was prevented by amlodipine but not atenolol. SHR showed a larger carotid artery diameter with impaired pulsatility, which was prevented by atenolol. Cerebral arteries demonstrated inward remodelling, stiffening and endothelial dysfunction in SHR. Both treatments similarly improved these parameters. MRI revealed that SHR have smaller brains with enlarged ventricles. In addition, neurofilament light levels were increased in cerebrospinal fluid of SHR. However, neither treatment affected these parameters. In conclusion, amlodipine and atenolol both lower blood pressure, but elicit a different hemodynamic profile. Both medications improve cerebral artery structure and function, but neither drug prevented indices of brain damage in this model of hypertension.
Topics: Rats; Animals; Antihypertensive Agents; Hypertension; Rats, Inbred SHR; Atenolol; Amlodipine; Hypotension; Rats, Inbred WKY; Carotid Artery, Common
PubMed: 36859481
DOI: 10.1038/s41598-023-30515-0 -
Clinical Hypertension Mar 2023Leigh syndrome is a progressive neurodegenerative mitochondrial disorder caused by multiple genetic etiologies with multisystemic involvement that mostly affecting the...
BACKGROUND
Leigh syndrome is a progressive neurodegenerative mitochondrial disorder caused by multiple genetic etiologies with multisystemic involvement that mostly affecting the central nervous system with high rate of premature mortality.
CASE PRESENTATION
We present a 3-year, 10 month-old female patient with Leigh syndrome complicated by renal tubular acidosis, hypertension, gross motor delay, who presented with hypertensive emergency, persistent tachycardia, insomnia and irritability. Her previous genetic workup revealed a pathogenic variant in the MT-ND5 gene designated as m.13513G > A;p.Asp393Asn with a heteroplasmy of 69%. She presented acutely with malignant hypertension requiring intensive care unit admission. Her acute evaluation revealed elevated serum and urine catecholamines, without an identifiable catecholamine-secreting tumor. After extensive evaluation for secondary causes, she was ultimately found to have progression of her disease with new infarctions in her medulla, pons, and basal ganglia as the most likely etiology of her hypertension. She was discharged home with clonidine, amlodipine and atenolol for hypertension management. This report highlights the need to recognize possible autonomic dysfunction in mitochondrial disease and illustrates the challenges for accurate and prompt diagnosis and subsequent management of the associated manifestations. This association between catecholamine induced autonomic dysfunction and Leigh syndrome has been previously reported only once with MT-ND5 mutation.
CONCLUSIONS
Elevated catecholamines with malignant secondary hypertension may be unique to this specific mutation or may be a previously unrecognized feature of Leigh syndrome and other mitochondrial complex I deficient syndromes. As such, patients with Leigh syndrome who present with malignant hypertension should be treated without the need for extensive work-up for catecholamine-secreting tumors.
PubMed: 36855210
DOI: 10.1186/s40885-022-00231-4 -
International Journal of Pharmaceutics:... Dec 2023The aim of this work was to assess the impact of solvent selection on the characteristics of niosomes prepared by microfluidic mixing. To achieve this, niosomes were...
The aim of this work was to assess the impact of solvent selection on the characteristics of niosomes prepared by microfluidic mixing. To achieve this, niosomes were manufactured using bench-scale microfluidic mixing systems by changing the type of aqueous and/or organic solvents used to prepare the particles. Niosomes were prepared using different non-ionic surfactants and cholesterol compositions with different solvents and evaluated to investigate the influence of organic and aqueous solvents on the particle's physiochemical characteristics. Here we demonstrated that the solvent selection is a key factor to be considered during the preparation of niosomes with microfluidic mixing. The type of organic solvent was shown to significantly affect the size and the size distribution of the prepared particles. In general, niosome size increased with increasing organic solvent polarity, without affecting the niosomes stability. Moreover, changing the aqueous solvent used to hydrate the lipid components significantly ( < 0.05) affected the characteristics of the prepared niosomes in terms of particles size, size distribution, and surface charge. This impact of solvent selection on the final product is dependent on the lipid components where niosomes prepared with different compositions will have different characteristics when changing the type of organic and/or aqueous solvents. The apparent encapsulation efficiency of quinine as a model hydrophobic drug was subsequently shown to be significantly ( < 0.05) affected by the type of the organic solvent used to prepare the niosomes, while the impact of the organic solvent had less impact on the apparent encapsulation of atenolol as a model hydrophilic drug.
PubMed: 36852395
DOI: 10.1016/j.ijpx.2023.100168 -
Circulation Journal : Official Journal... Mar 2023α/β- and β-blockers are essential in pregnant women's perinatal congenital heart disease management. Nevertheless, data on the effects of α/β- and β-blockers on...
BACKGROUND
α/β- and β-blockers are essential in pregnant women's perinatal congenital heart disease management. Nevertheless, data on the effects of α/β- and β-blockers on pregnant women and fetuses are limited. We examined the risks of neonatal hypoglycemia and small for gestational age (SGA) associated with maternal exposure to α/β- and β-blockers.Methods and Results: All consecutive pregnant women with heart disease admitted to our hospital between January 2014 and October 2020 were included. Of 306 pregnancies (267 women), 32 were in the α/β-blocker group, 11 were in the β-blocker group, and 263 were in the control group. All 32 pregnancies in the α/β-blocker group were treated with carvedilol. In the β-blocker group, 4 women were treated with bisoprolol, 3 were treated with propranolol, 2 were treated with atenolol, 1 was treated with metoprolol, and 1 was treated nadolol. The incidence of neonatal hypoglycemia was higher in pregnant women taking carvedilol than in the control group (P=0.025). SGA was observed significantly more frequently in pregnant women taking β-blockers than in the carvedilol and control groups (P<0.001).
CONCLUSIONS
Carvedilol administration during pregnancy was associated with neonatal hypoglycemia; however, it did not occur in a time- or dose-dependent manner. Routine monitoring of blood glucose levels in newborns exposed to α/β- and β-blockers is essential.
Topics: Female; Infant, Newborn; Humans; Pregnancy; Carvedilol; Gestational Age; Adrenergic beta-Antagonists; Metoprolol; Hypoglycemia
PubMed: 36823100
DOI: 10.1253/circj.CJ-22-0647 -
Scientific Reports Feb 2023The need for more efficient drug delivery strategies with ultraprecision and control over the release of drugs has led to the growth of more sophisticated drug-releasing...
The need for more efficient drug delivery strategies with ultraprecision and control over the release of drugs has led to the growth of more sophisticated drug-releasing systems as a promising alternative to conventional clinical therapies. This new seed of strategies has explored an encouraging property to overcome the inherent problems of traditional therapies. One of the major challenges for any drug delivery system is the introduction of a complete view of the delivery system. In this article, we intend to elucidate the theoretical proof of concept of the electrosynthesis ATN@DNA core-shell like structure as a model system. Therefore, we present a fractal kinetic model (non-exponential model) taking into consideration the concept of time-dependent diffusion coefficient, which was developed using a numerical method with the help of COMSOL Multiphysics. In addition to that, we present here a general fractional kinetic model in sense of the tempered fractional operator, which leads to better characterized memory properties of the release process. Also, the fractional model is compared with the fractal kinetic model and both offer a good description of drug release processes that present anomalous kinetics. The solutions of the fractal and fractional kinetic models are also fitted successfully with our real-release results.
Topics: Atenolol; Drug Delivery Systems; Drug Liberation; Pharmaceutical Preparations; Models, Biological
PubMed: 36813844
DOI: 10.1038/s41598-023-29774-8 -
Molecules (Basel, Switzerland) Jan 2023A capillary zone electrophoretic (CZE) method was developed, validated, and applied for the assay of metformin (MET) and pioglitazone (PIO) in pharmaceutical...
Development of Capillary Zone Electrophoresis Method for the Simultaneous Separation and Quantification of Metformin and Pioglitazone in Dosage Forms; and Comparison with HPLC Method.
A capillary zone electrophoretic (CZE) method was developed, validated, and applied for the assay of metformin (MET) and pioglitazone (PIO) in pharmaceutical formulations. The optimum running buffer composition was found to be 75 mmol/L phosphate buffer containing 30% acetonitrile (ACN) at pH 4.0. The optimum instrumental conditions were found to be injection time, 10 s; applied voltage, 25 kV; hydrodynamic injection pressure, 0.5 psi for 10 s, capillary temperature, 25 °C; and the detection wavelength, 210 nm. The quantifications were calculated based on the ratio of the peak areas of analytes to atenolol as an internal standard. The CZE method was validated in terms of accuracy (98.21-104.81%), intra- and inter-day precision of migration time and peak area (relative standard deviation ≤ 5%), linearity (correlation coefficients ≥ 0.9985), limit of detection (≤0.277 μg/mL), and limit of quantitation (≤0.315 μg/mL). The proposed method was applied for the analysis of PIO and MET both individually and in a combined dosage tablet formulation. All electrophoretic parameters were calculated and evaluated. A previously reported high-performance liquid chromatographic (HPLC) method was also applied to the same samples. A comprehensive comparison was then carried out for the analytical features of both methods CZE and HPLC. Comparable results were obtained with the advantage of reagent consumption and separation efficiency of CZE over HPLC and shorter analysis time by HPLC compared with CZE.
Topics: Pioglitazone; Chromatography, High Pressure Liquid; Metformin; Electrophoresis, Capillary; Tablets; Indicators and Reagents; Reproducibility of Results
PubMed: 36770850
DOI: 10.3390/molecules28031184 -
Journal of Clinical Hypertension... Mar 2023The authors performed a meta-analysis to assess the efficacy of non-atenolol β-blockers as add-on to monotherapy or as a component of combination antihypertensive... (Meta-Analysis)
Meta-Analysis
The authors performed a meta-analysis to assess the efficacy of non-atenolol β-blockers as add-on to monotherapy or as a component of combination antihypertensive therapy in patients with hypertension. The authors searched and identified relevant randomized controlled trials from PubMed until November 2021. Studies comparing blood pressure lowering effects of β-blockers with diuretics, calcium channel blockers (CCBs), angiotensin-converting enzyme inhibitors (ACEIs), or angiotensin receptor blockers (ARBs) were included. The analysis included 20 studies with 5544 participants. β-blockers add-on to monotherapy significantly reduced systolic and diastolic blood pressure as compared with non-β-blocker monotherapy (weighted mean difference in mm Hg [95% confidence interval]: -4.1 [-6.0, -2.2] and -3.7 [-4.6, -2.8], respectively). These results were consistent across the comparisons with diuretics (systolic pressure, -10.2 [-14.2, -6.2]; diastolic pressure, -5.4 [-8.2, -2.6]), CCBs (systolic pressure, -4.1 [-7.1, -1.0]; diastolic pressure, -2.8 [-4.1, -1.5]), and ACEIs/ARBs (systolic pressure, -2.9 [-4.3, -1.5]; diastolic pressure, -4.2 [-5.0, -3.4]). There was no significant difference in blood pressure lowering effects between combinations with and without a β-blocker (systolic pressure, -1.3 mm Hg [-5.8, 3.2]; diastolic pressure, -.3 mm Hg [-2.7, 2.1]). Metoprolol add-on or combination therapy had a significantly greater blood pressure reduction than non-β-blocker therapy (systolic pressure, -3.6 mm Hg [-5.9, -1.3]; diastolic pressure, -2.1 mm Hg [-3.5, -.7]). In conclusion, non-atenolol β-blockers are effective in lowering blood pressure as add-on to monotherapy or as a component of combination antihypertensive therapy. In line with the current hypertension guideline recommendations, β-blockers can and should be used in combination with other antihypertensive drugs.
Topics: Humans; Blood Pressure; Antihypertensive Agents; Hypertension; Angiotensin-Converting Enzyme Inhibitors; Angiotensin Receptor Antagonists; Randomized Controlled Trials as Topic; Calcium Channel Blockers; Adrenergic beta-Antagonists; Diuretics
PubMed: 36756690
DOI: 10.1111/jch.14616