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Psychopharmacology Mar 2024Although the study of emotions can look back to over 100 years of research, it is unclear which information the brain uses to construct the subjective experience of an...
RATIONALE
Although the study of emotions can look back to over 100 years of research, it is unclear which information the brain uses to construct the subjective experience of an emotion.
OBJECTIVE
In the current study, we assess the role of the peripheral and central adrenergic system in this respect.
METHODS
Healthy volunteers underwent a double inhalation of 35% CO, which is a well-validated procedure to induce an intense emotion, namely panic. In a randomized, cross-over design, 34 participants received either a β-blocker acting selectively in the peripheral nervous system (atenolol), a β-blocker acting in the peripheral and central nervous system (metoprolol), or a placebo before the CO inhalation.
RESULTS
Heart rate and systolic blood pressure were reduced in both β-blocker conditions compared to placebo, showing effective inhibition of the adrenergic tone. Nevertheless, the subjective experience of the induced panic was the same in all conditions, as measured by self-reported fear, discomfort, and panic symptom ratings.
CONCLUSIONS
These results indicate that information from the peripheral and central adrenergic system does not play a major role in the construction of the subjective emotion.
Topics: Humans; Adrenergic beta-Antagonists; Carbon Dioxide; Emotions; Fear; Heart Rate; Panic; Nervous System
PubMed: 38363344
DOI: 10.1007/s00213-024-06548-2 -
European Heart Journal Apr 2024Visit-to-visit systolic blood pressure variability (BPV) is an important predictor of cardiovascular (CV) outcomes. The long-term effect of a period of blood pressure...
BACKGROUND AND AIMS
Visit-to-visit systolic blood pressure variability (BPV) is an important predictor of cardiovascular (CV) outcomes. The long-term effect of a period of blood pressure (BP) control, but with differential BPV, is uncertain. Morbidity and mortality follow-up of UK participants in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure-Lowering Arm has been extended for up to 21 years to determine the CV impact of mean systolic blood pressure (SBP) control and BPV during the trial, and amongst those allocated to amlodipine- and atenolol-based treatment.
METHODS
Eight thousand five hundred and eighty hypertensive participants (4305 assigned to amlodipine ± perindopril-based and 4275 to atenolol ± diuretic-based treatment during the in-trial period (median 5.5 years) were followed for up to 21 years (median 17.4 years), using linked hospital and mortality records. A subgroup of participants (n = 2156) was followed up 6 years after the trial closure with a self-administered questionnaire and a clinic visit. In-trial mean SBP and standard deviation of visit-to-visit SBP as a measure of BPV, were measured using >100 000 BP measurements. Cox proportional hazard models were used to estimate the risk [hazard ratios (HRs)], associated with (i) mean with SBP and BPV during the in-trial period, for the CV endpoints occurring after the end of the trial and (ii) randomly assigned treatment to events following randomization, for the first occurrence of pre-specified CV outcomes.
RESULTS
Using BP data from the in-trial period, in the post-trial period, although mean SBP was a predictor of CV outcomes {HR per 10 mmHg, 1.14 [95% confidence interval (CI) 1.10-1.17], P < .001}, systolic BPV independent of mean SBP was a strong predictor of CV events [HR per 5 mmHg 1.22 (95% CI 1.18-1.26), P < .001] and predicted events even in participants with well-controlled BP. During 21-year follow-up, those on amlodipine-based compared with atenolol-based in-trial treatment had significantly reduced risk of stroke [HR 0.82 (95% CI 0.72-0.93), P = .003], total CV events [HR 0.93 (95% CI 0.88-0.98), P = .008], total coronary events [HR 0.92 (95% CI 0.86-0.99), P = .024], and atrial fibrillation [HR 0.91 (95% CI 0.83-0.99), P = .030], with weaker evidence of a difference in CV mortality [HR 0.91 (95% CI 0.82-1.01), P = .073]. There was no significant difference in the incidence of non-fatal myocardial infarction and fatal coronary heart disease, heart failure, and all-cause mortality.
CONCLUSIONS
Systolic BPV is a strong predictor of CV outcome, even in those with controlled SBP. The long-term benefits of amlodipine-based treatment compared with atenolol-based treatment in reducing CV events appear to be primarily mediated by an effect on systolic BPV during the trial period.
Topics: Humans; Blood Pressure; Atenolol; Antihypertensive Agents; Hypertension; Amlodipine; Risk Factors
PubMed: 38291599
DOI: 10.1093/eurheartj/ehad814 -
Dermatology (Basel, Switzerland) 2024Infants with infantile hemangioma (IH) have been effectively treated with propranolol or atenolol. Concerns were raised about the mental health of these children at...
BACKGROUND
Infants with infantile hemangioma (IH) have been effectively treated with propranolol or atenolol. Concerns were raised about the mental health of these children at school age, due to central nervous system effects of propranolol and visible nature of IH.
OBJECTIVE
This study aimed to compare the mental health at school age of children treated with propranolol to children treated with atenolol for IHs and their parents.
METHODS
This two-centered cross-sectional study included children aged ≥6 years and treated with either propranolol or atenolol for IH during infancy. Children's outcomes were performance-based affect recognition (Dutch version of the Developmental Neuropsychological Assessment-II [NEPSY-II-NL]), parent-reported emotional and behavioral functioning (Child Behavioral Checklist [CBCL]), and health-related quality of life (KIDSCREEN-27). Parents' outcome was parenting stress (Parenting Stress Questionnaire [OBVL]).
RESULTS
Data of 105 children (36 propranolol, 69 atenolol; 6.0-11.8 years) were analyzed. Mental health outcomes did not differ between both β-blocker groups. Although overall functioning was in line with norms, children presented specific problems concerning affect recognition, parent-reported attention, and social quality of life. Parents showed increased physical symptoms, depressive symptoms, and parent-child relationship problems.
CONCLUSION
No difference in mental health at school age was found between children treated with propranolol or atenolol for IH. Although few overall mental health problems were found, specific problems require follow-up. Follow-up of children should be directed toward affect recognition, attention, and social functioning in daily life. Problems reported by parents could be ameliorated by mental health support during and after their infant's β-blocker treatment.
Topics: Infant; Humans; Child; Atenolol; Propranolol; Mental Health; Cross-Sectional Studies; Quality of Life; Hemangioma, Capillary; Adrenergic beta-Antagonists; Parents
PubMed: 38228125
DOI: 10.1159/000536144 -
Biomedicine & Pharmacotherapy =... Feb 2024Telmisartan is an antagonist of the angiotensin II receptor used in the management of hypertension (alone or in combination with other antihypertensive agents. It... (Review)
Review
Telmisartan is an antagonist of the angiotensin II receptor used in the management of hypertension (alone or in combination with other antihypertensive agents. It belongs to the drug class of angiotensin II receptor blockers (ARBs). Among drugs of this class, telmisartan shows particular pharmacologic properties, including a longer half-life than any other angiotensin II receptor blockers that bring higher and persistent antihypertensive activity. In hypertensive patients, telmisartan has superior efficacy than other antihypertensive drugs (losartan, valsartan, ramipril, atenolol, and perindopril) in controlling blood pressure, especially towards the end of the dosing interval. Telmisartan has a partial PPARγ-agonistic effect whilst does not have the safety concerns of full agonists of PPARγ receptors (thiazolidinediones). Moreover, telmisartan has an agonist activity on PPARα and PPARδ receptors and modulates the adipokine levels. Thus, telmisartan could be considered as a suitable alternative option, with multi-benefit for all components of metabolic syndrome including hypertension, diabetes mellitus, obesity, and hyperlipidemia. This review will highlight the role of telmisartan in metabolic syndrome and the main mechanisms of action of telmisartan are discussed and summarized. Many studies have demonstrated the useful properties of telmisartan in the prevention and improving of metabolic syndrome and this well-tolerated drug can be greatly proposed in the treatment of different components of metabolic syndrome. However, larger and long-duration studies are needed to confirm these findings in long-term observational studies and prospective trials and to determine the optimum dose of telmisartan in metabolic syndrome.
Topics: Humans; Telmisartan; Angiotensin Receptor Antagonists; Metabolic Syndrome; PPAR gamma; Prospective Studies; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Benzimidazoles; Hypertension; Antihypertensive Agents; Blood Pressure; Benzoates
PubMed: 38228033
DOI: 10.1016/j.biopha.2024.116169 -
Heliyon Dec 2023In this work, gold nanoparticles coated with polyvinylpyrrolidone (PVP-AuNPs) were used as a colorimetric probe for the sensitive, selective, simple, and rapid...
In this work, gold nanoparticles coated with polyvinylpyrrolidone (PVP-AuNPs) were used as a colorimetric probe for the sensitive, selective, simple, and rapid determination of atenolol (ATN). Indeed, atenolol triggered the aggregation of PVP-AuNPs via hydrogen bonding, electrostatic interactions, and dipole-dipole forces with PVP on the surface of AuNPs, causing the colloidal solution's color to shift from red to blue. SEM, TEM, FT-IR, UV-Vis, zeta potential, and other methods were used to characterise the PVP-AuNPs that were created as well as their aggregates. An excellent linear relationship between the absorption ratio (A690/A521) and the concentration of ATN in the range of 0.07-3.0 μM with a detection limit of 0.023 μM was discovered by optimising the experimental settings. The influence of potential interfering species on the measurement of ATN was investigated, and it was discovered that the developed colorimetric sensor had satisfactory selectivity. Finally, the presented method was used to measure ATN in tablet and blood plasma samples, and the obtained recovery values showed great promise for the use of the proposed sensor in clinical applications.
PubMed: 38213583
DOI: 10.1016/j.heliyon.2023.e22675 -
Biological & Pharmaceutical Bulletin 2024We recently reported that the gastrointestinal (GI) fluid volume is influenced by the solution osmolality, and proposed that this effect may play a role in beverage-drug...
We recently reported that the gastrointestinal (GI) fluid volume is influenced by the solution osmolality, and proposed that this effect may play a role in beverage-drug interactions. Here, we investigated whether osmolality-dependent fluid secretion can explain the difference in the magnitudes of fruit juice-drug interactions depending on the type of fruit juice (grapefruit juice (GFJ), orange juice (OJ), and apple juice (AJ)). The osmolality of GFJ, OJ, and AJ used in this study was found to be 552, 686, and 749 mOsm/kg, respectively. Measurements of intestinal fluid movement following beverage administration by the in situ closed-loop technique revealed the following rank order for fluid volume in rat ileum: AJ > OJ > GFJ > purified water, suggesting that water movement is dependent on the osmolality of these beverages. Such changes in GI fluid volume are expected to alter the luminal drug concentration, potentially contributing to the magnitude of beverage-drug interactions. Indeed, in vivo pharmacokinetic study in rats revealed that the plasma concentration of atenolol, a low-permeability drug, was the highest after oral administration in purified water, followed by GFJ and OJ, and was the lowest after administration in AJ. In contrast, antipyrine, a high-permeability drug, showed no significant difference in plasma concentration after administration in purified water and fruit juices, suggesting that the absorption of high-permeability drugs is less affected by solution osmolality. Our findings indicate that differences in the magnitude of beverage-drug interactions can be at least partly explained by differences in the osmolality of the beverages ingested.
Topics: Rats; Animals; Malus; Fruit and Vegetable Juices; Citrus paradisi; Citrus sinensis; Food-Drug Interactions; Beverages; Osmolar Concentration; Water; Fruit
PubMed: 38171780
DOI: 10.1248/bpb.b23-00490 -
Cureus Nov 2023Supraventricular tachycardia (SVT) is the most common tachyarrhythmia of pregnancy. Catecholamine surges, the use of vasoactive agents during delivery, and increased...
Supraventricular tachycardia (SVT) is the most common tachyarrhythmia of pregnancy. Catecholamine surges, the use of vasoactive agents during delivery, and increased cardiac output during pregnancy are the most common contributing factors to developing SVT. SVT is usually benign in presentation but can lead to more serious arrhythmias in patients with a history of mitral stenosis secondary to rheumatic heart disease. When an SVT is detected, organic heart causes should be ruled out first. Symptoms of SVT include shortness of breath, palpitations, syncope, sweating, chest pain, and dizziness. In patients who are refractory to pharmacologic management and hemodynamically unstable, electrical cardioversion has proven to be efficacious and safe in all trimesters. The initial treatment for hemodynamically stable patients is to attempt vagal maneuvers, such as carotid sinus massage or Valsalva maneuver. If the SVT does not convert to normal sinus rhythm, treatment with adenosine or beta-blockers may be initiated. Treatment with atenolol and verapamil should be avoided due to their teratogenic effects.
PubMed: 38143604
DOI: 10.7759/cureus.49256 -
Heliyon Dec 2023To determine the concentrations of nine drugs used in the treatment of cardiovascular diseases in human plasma through QuEChERS pre-treatment combined with...
To determine the concentrations of nine drugs used in the treatment of cardiovascular diseases in human plasma through QuEChERS pre-treatment combined with ultra-performance liquid chromatography-tandem mass spectrometry. Plasma samples were extracted with 3 mL of acetonitrile, 400 mg of anhydrous magnesium sulfate as a salting agent, and 20 mg of C18 as a sorbent. An Agilent Poroshell 120 EC-C18 column (4.6 × 100 mm, 2.7 μm) was selected and methanol-0.1 % water was used as the mobile phase, and ESI positive ion detection mode was selected. Results: The plasma concentrations of nisoldipine, metoprolol, and prazosin exhibited good linearity within the range of 0.05-4.0 ng/mL (r > 0.99), while atenolol, bisoprolol, propranolol, rosuvastatin, and atorvastatin showed linearity within the range of 0.5-40 ng/mL (r > 0.99). Fluvastatin showed good linearity within the range of 5.0-400 ng/mL. The accuracy of the method ranged from 94.15 to 110.62 %, while the recovery levels were in the range of 85.23 %-115.13 %. The matrix effects were observed between-6.54 % and 12.43 %. The intra-day and inter-day RSD was <15 % for the three concentrations of low, medium, and high. Conclusion The proposed method is rapid, accurate, specific, simple, reproducible, and suitable for the simultaneous measurement of the concentrations of nine drugs used in the treatment of cardiovascular diseases in human plasma.
PubMed: 38094060
DOI: 10.1016/j.heliyon.2023.e22543 -
PloS One 2023Co-existence of life style disorders, like, Diabetes or Hypertension, increases risk of, treatment failure, deaths and developing drug-resistant TB. Concomitant...
Co-existence of life style disorders, like, Diabetes or Hypertension, increases risk of, treatment failure, deaths and developing drug-resistant TB. Concomitant administration of drugs to treat dual/multi-morbidities may alter their effectiveness, in additive/synergistic or adverse/antagonistic manner. We evaluated interactive effect of 7 anti-hyperglycaemic (HG) and 6 anti-hypertensive (HT) drugs on the inhibitory (MICs) and bactericidal (% killing of intracellular bacilli) activities of anti-TB drugs, Isoniazid (INH), Rifampicin (RFM), Ethambutol (EMB) and Streptomycin (STR) against M. tuberculosis. Five anti-HG drugs, namely, Acarbose, Acetohexamide, Glyburide, Repaglinide and Sitagliptin imparted either 'additive' or 'no effect' on the activities (inhibition or % killing) of all the four anti-TB drugs, as evident by their lower FICs (Fractional Inhibitory concentrations) and higher bacterial killing in combination. Metformin and Rosiglitazone, however, exerted adverse effect on the Ethambutol (FICs >2.0). All the six anti-HT drugs, namely, Atenolol, Hydrochlorothiazide, Ramipril, Valsartan, Nifedipine and Verapamil exerted either 'additive'/'synergistic' or 'no effect' on the activities of anti-TB drugs. These findings may help clinicians to select safe and helpful anti-HG or anti-HT drugs for TB patients, if, suffering with diabetes or hypertension like co-morbidities and receiving DOTs (a set regimen for the treatment of TB based on the WHO guidelines).
Topics: Humans; Antitubercular Agents; Antihypertensive Agents; Ethambutol; Pharmaceutical Preparations; Mycobacterium tuberculosis; Isoniazid; Microbial Sensitivity Tests; Tuberculosis; Hypertension; Diabetes Mellitus; Hypoglycemic Agents; Tuberculosis, Multidrug-Resistant
PubMed: 38032920
DOI: 10.1371/journal.pone.0292397 -
Pharmaceuticals (Basel, Switzerland) Oct 2023Although patients would rather oral therapies to injections, the gastrointestinal tract's low permeability makes this method limiting for most compounds, including...
Although patients would rather oral therapies to injections, the gastrointestinal tract's low permeability makes this method limiting for most compounds, including anticancer drugs. Due to their low bioavailability, oral antitumor therapies suffer from significant variability in pharmacokinetics and efficacy. The improvement of their pharmacokinetic profiles can be achieved by a new approach: the use of natural extracts enriched with polyphenolic compounds that act as intestinal permeability enhancers. Here, we propose a safe sweet cherry extract capable of enhancing oral absorption. The extract was characterized by the HPLC-UV/MS method, evaluated for in vitro antioxidant activity, safety on the Caco-2 cell line, and as a potential permeation enhancer. The sweet cherry extract showed a high antioxidant capacity (ABTS and DPPH assays were 211.74 and 48.65 µmol of Trolox equivalent/g dried extract, respectively), high content of polyphenols (8.44 mg of gallic acid per gram of dry extract), and anthocyanins (1.80 mg of cyanidin-3-glucoside equivalent per g of dry extract), reassuring safety profile (cell viability never lower than 98%), and a significant and fully reversible ability to alter the integrity of the Caco-2 monolayer (+81.5% of Lucifer yellow permeability after 2 h). Furthermore, the ability of the sweet cherry extract to improve the permeability (P) and modify the efflux ratio (ER) of reference compounds (atenolol, propranolol, and dasatinib) and selected pyrazolo[3,4-]pyrimidine derivatives was investigated. The obtained results show a significant increase in apparent permeability across the Caco-2 monolayer (tripled and quadrupled in most cases), and an interesting decrease in efflux ratio when compounds were co-incubated with sweet cherry extract.
PubMed: 38004393
DOI: 10.3390/ph16111527