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The impact of propranolol on nitric oxide and total antioxidant capacity in patients with resistant hypertension-evidence from the APPROPRIATE trial.
Ranasinghe, HN, Fernando, N, Handunnetti, S, Weeratunga, PN, Katulanda, P, Rajapakse, S, Galappatthy, P, Constantine, GR
BMC research notes. 2020;(1):228
Abstract
OBJECTIVES The objective was to assess the effect of propranolol on oxidative stress and anti-oxidant potential in patients with resistant hypertension as a secondary analysis of the APPROPRIATE trial. This randomized double blinded clinical trial recruited patients with resistant hypertension and allocated forty patients to propranolol and placebo in 1:1 ratio. The pro-oxidant state (nitrate and nitrite) was assessed using modified Griess assay. The total anti-oxidant capacity was measured using ABTS assay. RESULTS Analysis was performed for 18 patients from the propranolol group and 15 from the placebo group. A decline in end point ambulatory blood pressure (p = 0.031) and greater mean reduction in office SBP (29.7 ± 13.0 mmHg, p = 0.021) was noted in the propranolol arm. Nitrate and nitrite levels were lower at the end of a 90 day follow up period in both arms, with a greater mean reduction with propranolol. A significant increase in the AOC was noted in both arms with higher incremental value with Propranolol. The findings of this study do not demonstrate a statistically significant effect of propranolol on the oxidative stress/antioxidant balance in patients with resistant hypertension. The observed trends merit further evaluation.
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Association of Weight-Adjusted Caffeine and β-Blocker Use With Ophthalmology Fellow Performance During Simulated Vitreoretinal Microsurgery.
Roizenblatt, M, Dias Gomes Barrios Marin, V, Grupenmacher, AT, Muralha, F, Faber, J, Jiramongkolchai, K, Gehlbach, PL, Farah, ME, Belfort, R, Maia, M
JAMA ophthalmology. 2020;(8):819-825
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IMPORTANCE Vitreoretinal surgery can be technically challenging and is limited by physiologic characteristics of the surgeon. Factors that improve accuracy and precision of the vitreoretinal surgeon are invaluable to surgical performance. OBJECTIVES To establish weight-adjusted cutoffs for caffeine and β-blocker (propranolol) intake and to determine their interactions in association with the performance of novice vitreoretinal microsurgeons. DESIGN, SETTINGS, AND PARTICIPANTS This single-blind cross-sectional study of 15 vitreoretinal surgeons who had less than 2 years of surgical experience was conducted from September 19, 2018, to September 25, 2019, at a dry-laboratory setting. Five simulations were performed daily for 2 days. On day 1, performance was assessed after sequential exposure to placebo, low-dose caffeine (2.5 mg/kg), high-dose caffeine (5.0 mg/kg), and high-dose propranolol (0.6 mg/kg). On day 2, performance was assessed after sequential exposure to placebo, low-dose propranolol (0.2 mg/kg), high-dose propranolol (0.6 mg/kg), and high-dose caffeine (5.0 mg/kg). INTERVENTIONS Surgical simulation tasks were repeated 30 minutes after masked ingestion of placebo, caffeine, or propranolol pills during the 2 days. MAIN OUTCOMES AND MEASURES An Eyesi surgical simulator was used to assess surgical performance, which included surgical score (range, 0 [worst] to 700 [best]), task completion time, intraocular trajectory, and tremor rate (range, 0 [worst] to 100 [best]). The nonparametric Friedman test followed by Dunn-Bonferroni post hoc test was applied for multiple comparisons. RESULTS Of 15 vitreoretinal surgeons, 9 (60%) were male, with a mean (SD) age of 29.6 (1.4) years and mean (SD) body mass index (calculated as weight in kilograms divided by height in meters squared) of 23.15 (2.9). Compared with low-dose propranolol, low-dose caffeine was associated with a worse total surgical score (557.0 vs 617.0; difference, -53.0; 95% CI, -99.3 to -6.7; P = .009), a lower antitremor maneuver score (55.0 vs 75.0; difference, -12.0; 95% CI, -21.2 to -2.8; P = .009), longer intraocular trajectory (2298.6 vs 2080.7 mm; difference, 179.3 mm; 95% CI, 1.2-357.3 mm; P = .048), and increased task completion time (14.9 minutes vs 12.7 minutes; difference, 2.3 minutes; 95% CI, 0.8-3.8 minutes; P = .048). Postcaffeine treatment with propranolol was associated with performance improvement; however, surgical performance remained inferior compared with low-dose propranolol alone for total surgical score (570.0 vs 617.0; difference, -51.0; 95% CI, -77.6 to -24.4; P = .01), tremor-specific score (50.0 vs 75.0; difference, -16.0; 95% CI, -31.8 to -0.2; P = .03), and intraocular trajectory (2265.9 mm vs 2080.7 mm; difference, 166.8 mm; 95% CI, 64.1-269.6 mm; P = .03). CONCLUSIONS AND RELEVANCE The findings suggest that performance of novice vitreoretinal surgeons was worse after receiving low-dose caffeine alone but improved after receiving low-dose propranolol alone. Their performance after receiving propranolol alone was better than after the combination of propranolol and caffeine. These results may be helpful for novice vitreoretinal surgeons to improve microsurgical performance.
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Study protocol: safety and efficacy of propranolol 0.2% eye drops in newborns with a precocious stage of retinopathy of prematurity (DROP-ROP-0.2%): a multicenter, open-label, single arm, phase II trial.
Filippi, L, Cavallaro, G, Berti, E, Padrini, L, Araimo, G, Regiroli, G, Bozzetti, V, De Angelis, C, Tagliabue, P, Tomasini, B, et al
BMC pediatrics. 2017;(1):165
Abstract
BACKGROUND Retinopathy of prematurity (ROP) still represents one of the leading causes of visual impairment in childhood. Systemic propranolol has proven to be effective in reducing ROP progression in preterm newborns, although safety was not sufficiently guaranteed. On the contrary, topical treatment with propranolol eye micro-drops at a concentration of 0.1% had an optimal safety profile in preterm newborns with ROP, but was not sufficiently effective in reducing the disease progression if administered at an advanced stage (during stage 2). The aim of the present protocol is to evaluate the safety and efficacy of propranolol 0.2% eye micro-drops in preterm newborns at a more precocious stage of ROP (stage 1). METHODS A multicenter, open-label, phase II, clinical trial, planned according to the Simon optimal two-stage design, will be performed to analyze the safety and efficacy of propranolol 0.2% eye micro-drops in preterm newborns with stage 1 ROP. Preterm newborns with a gestational age of 23-32 weeks, with a stage 1 ROP will receive propranolol 0.2% eye micro-drops treatment until retinal vascularization has been completed, but for no longer than 90 days. Hemodynamic and respiratory parameters will be continuously monitored. Blood samplings checking metabolic, renal and liver functions, as well as electrocardiogram and echocardiogram, will be periodically performed to investigate treatment safety. Additionally, propranolol plasma levels will be measured at the steady state, on the 10th day of treatment. To assess the efficacy of topical treatment, the ROP progression from stage 1 ROP to stage 2 or 3 with plus will be evaluated by serial ophthalmologic examinations. DISCUSSION Propranolol eye micro-drops could represent an ideal strategy in counteracting ROP, because it is definitely safer than oral administration, inexpensive and an easily affordable treatment. Establishing the optimal dosage and treatment schedule is to date a crucial issue. TRIAL REGISTRATION ClinicalTrials.gov Identifier NCT02504944, registered on July 19, 2015, updated July 12, 2016. EudraCT Number 2014-005472-29.
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Trauma reactivation plus propranolol is associated with durably low physiological responding during subsequent script-driven traumatic imagery.
Brunet, A, Thomas, É, Saumier, D, Ashbaugh, AR, Azzoug, A, Pitman, RK, Orr, SP, Tremblay, J
Canadian journal of psychiatry. Revue canadienne de psychiatrie. 2014;(4):228-32
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OBJECTIVE In a previous, double-blind, placebo-controlled study, patients with posttraumatic stress disorder (PTSD) showed lower physiological response during script-driven traumatic imagery 1 week after receiving a single dose of propranolol given after the retrieval of a traumatic memory. We hypothesized that this effect would extend beyond 1 week using a modified treatment approach. METHOD Twenty-eight participants with PTSD read an account of their traumatic event once weekly for 6 consecutive weeks under the influence of open-label propranolol. One week and 4-months later, skin conductance, heart rate, and left corrugator electromyogram responses were measured while participants engaged in script-driven mental imagery of their traumatic event. Results from the 22 study participants were compared with results from treated and untreated participants in a previously published trial. RESULTS Most participants in our study were classified as non-PTSD cases at posttreatment and follow-up according to a psychophysiological discriminant function analysis. Posttreatment skin conductance and heart rate responses of the current (propranolol-treated) participants were lower than those of placebo participants from the previous study. No difference was observed between physiological responding measured posttreatment and at follow-up. CONCLUSIONS Low physiological responding during script-driven traumatic imagery after treatment extends up to 4 months, demonstrating the durability of the treatment effect's. Limitations include the absence of a placebo-controlled group and lack of physiological baseline measures. Despite these limitations, results point to the need for future trials examining the clinical efficacy of trauma reactivation plus propranolol, as it has the potential to become a novel, cost- and time-effective treatment for PTSD.
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Modulation by cationic amphiphilic drugs of serine base-exchange, phosholipase d and intracellular calcium homeostasis in glioma C6 cells.
Bobeszko, M, Czajkowski, R, Wójcik, M, Sabała, P, Lei, L, Nalepa, I, Barańska, J
Polish journal of pharmacology. 2002;(5):483-93
Abstract
We aimed to assess the effect of three drugs belonging to amphiphilic cations, imipramine, amitriptyline and propranolol, on lipid synthesis and intracellular calcium homeostasis in glioma C6 cells. Antidepressants, imipramine and amitriptyline, had a stimulatory effect on [14C]serine incorporation into phosphatidylserine. Similar effect was induced by propranolol, antidysrhythmic drug and an antagonist of beta-adrenergic receptor, but not by isoproterenol, a selective agonist of this receptor. Stimulation of serine base-exchange activity by amphiphilic cations occured at concentration as low as 5-25 microM that may be reached during clinical treatment. At much higher concentration (250 microM), those drugs also stimulated phospholipase D-mediated synthesis of [14C]phosphatidylethanol and blocked phorbol ester-induced, protein kinase C-dependent phospholipase D activity. The latter effect already occurred at low (25 microM) concentration of drugs. We have also shown that treatment of the cells with amphiphilic cations (1 mM) produced only a weak increase in the intracellular Ca2+ concentration and did not affect Ca2+ release from the intracellular stores evoked by nucleotide receptor agonists, ATP and ADP. In contrast, this treatment strongly diminished an unspecific leak of Ca2+ from the endoplasmic reticulum caused by thapsigargin and ionomycin. Mianserin, which is not cationic amphiphilic drug, did not affect phosphatidylserine synthesis and phospholipase D activity and produced heterogenous and chaotic Ca2+ responses. Our results suggest that imipramine, amitriptyline and propranolol may modulate lipid synthesis and intracellular calcium signaling independently of their action on membrane receptors, most probably by modification of the physicochemical properties of cell membranes.
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Oxygen consumption in patients with hyperthyroidism before and after treatment with beta-blockade versus thyrostatic treatment: a prospective randomized study.
Jansson, S, Lie-Karlsen, K, Stenqvist, O, Körner, U, Lundholm, K, Tisell, LE
Annals of surgery. 2001;(1):60-4
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OBJECTIVE To evaluate randomly the effect of thyrostatic treatment (tiamazole) versus selective (metoprolol) and nonselective beta-blockade (propranolol) on whole-body energy metabolism in women with hyperthyroidism. SUMMARY BACKGROUND DATA beta-blockade is used as an alternative to thyrostatic drugs in the preoperative treatment of patients with hyperthyroidism. beta-blockers have well-established symptomatic effects, but in contrast to antithyroid drugs beta-blockade is thought to lack direct effects on the increased metabolism in hyperthyroidism. METHODS Whole-body oxygen consumption and carbon dioxide production was measured in a semiopen canopy system with paramagnetic O2 and infrared CO2 sensors. A constant flow generator and the gas-dilution method for calculation of gas flow were used. Anabolic parameters were body weight, triceps skinfold, and arm muscle circumference. RESULTS Tiamazole normalized oxygen consumption and induced signs of anabolism with improved nutritional state. Metroprolol did not affect oxygen consumption. Propranolol reduced elevated oxygen consumption by 54%. Body weight and other anthropometric assessments were stable after specific and nonspecific beta-blockade, which also led to symptomatic relief in approximately 90% of the patients. CONCLUSION Tiamazole was the most effective drug to oppose the adverse effects of hyperthyroidism. Therefore, thyrostatic agents are recommended for preoperative treatments of patients with severe catabolic hyperthyroidism. Whenever beta-blockers are chosen for treatment of hyperthyroidism, propranolol (beta 1 + beta 2) has an advantage because it reduces the metabolic rate, whereas selective beta 1-blockade seemed to provide only symptomatic relief, related to the normalization of heart rate.
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A comparative study of the elective treatment of variceal hemorrhage with beta-blockers, transendoscopic sclerotherapy, and surgery: a prospective, controlled, and randomized trial during 10 years.
Orozco, H, Mercado, MA, Chan, C, Guillén-Navarro, E, López-Martínez, LM
Annals of surgery. 2000;(2):216-9
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OBJECTIVE To compare three options for the elective treatment of portal hypertension during a 10-year period. METHODS Patients included in the trial were 18 to 76 years old, had a history of bleeding portal hypertension, and had undergone no prior treatment. Treatment options were beta-blockers (propranolol), sclerotherapy, and portal blood flow-preserving procedures (selective shunts and the Sugiura-Futagawa operation). RESULTS A total of 119 patients were included: 40 in the pharmacology group, 46 in the sclerotherapy group,and 33 in the surgical group. The three groups showed no differences in terms of age, Child-Pugh classification, and cause of liver disease. The rebleeding rate was significantly lower in the surgical group than in the other two groups. The rebleeding rate was only 5% in the Child A surgical group, compared with 71% and 68% for the sclerotherapy and pharmacotherapy groups, respectively. Survival was better for the low-risk patients (Child A) in the three groups, but when the three options were compared, no significant difference was found. CONCLUSIONS Portal blood flow-preserving procedures offer the lowest rebleeding rate in low-risk patients undergoing elective surgery.