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BioRxiv : the Preprint Server For... May 2024Propranolol reduces experimental murine cerebral cavernous malformations (CCMs) and prevents embryonic caudal venous plexus (CVP) lesions in zebrafish that follow mosaic...
Propranolol reduces experimental murine cerebral cavernous malformations (CCMs) and prevents embryonic caudal venous plexus (CVP) lesions in zebrafish that follow mosaic inactivation of . Because morpholino silencing of the β1 adrenergic receptor () prevents the embryonic CVP lesion, we proposed that plays a role in CCM pathogenesis. Here we report that zebrafish exhibited 86% fewer CVP lesions and 87% reduction of CCM lesion volume relative to wild type brood mates at 2dpf and 8-10 weeks stage, respectively. Treatment with metoprolol, a β1 selective antagonist, yielded a similar reduction in CCM lesion volume. zebrafish embryos exhibited reduced heart rate and contractility and reduced CVP blood flow. Similarly, slowing the heart and eliminating the blood flow in CVP by administration of 2,3-BDM suppressed the CVP lesion. In sum, our findings provide genetic and pharmacological evidence that the therapeutic effect of propranolol on CCM is achieved through β1 receptor antagonism.
PubMed: 38746306
DOI: 10.1101/2024.05.05.592554 -
Frontiers in Pharmacology 2024Prolonged QT intervals are extremely common in patients with cirrhosis and affect their treatment outcomes. Propranolol is often used to prevent gastroesophageal...
BACKGROUND
Prolonged QT intervals are extremely common in patients with cirrhosis and affect their treatment outcomes. Propranolol is often used to prevent gastroesophageal variceal hemorrhage in patients with cirrhosis; however, it is uncertain whether propranolol exerts a corrective effect on QT interval prolongation in patients with cirrhosis.
AIM
The study aimed to investigate the therapeutic effects of propranolol on patients with cirrhosis and prolonged QT intervals.
METHODS
A retrospective cohort study approach was adopted. Patients with cirrhosis complicated by moderate-to-severe gastroesophageal varices, who were hospitalized at the Affiliated Hospital of Guangdong Medical University between 1 December 2020 and 31 November 2022, were included in the study. The patients were divided into the propranolol and control groups based on whether they had received propranolol. Upon admission, the patients underwent tests on liver and kidney functions, electrolytes, and coagulation function, as well as abdominal ultrasonography and electrocardiography. In addition to conventional treatment, the patients were followed up after the use or non-use of propranolol for treatment and subsequently underwent reexamination of the aforementioned tests.
RESULTS
The propranolol group (26 patients) had an average baseline corrected QT (QTc) interval of 450.23 ± 37.18 ms, of which 14 patients (53.8%) exhibited QTc interval prolongation. Follow-up was continued for a median duration of 7.00 days after the administration of propranolol and conventional treatment. Electrocardiographic reexamination revealed a decrease in the QTc interval to 431.04 ± 34.64 ms ( = 0.014), and the number of patients with QTc interval prolongation decreased to five (19.2%; < 0.001). After treatment with propranolol and multimodal therapy, QTc interval normalization occurred in nine patients with QTc interval prolongation, leading to a normalization rate of 64.3% (9/14). The control group (n = 58) had an average baseline QTc interval of 453.74 ± 30.03 ms, of which 33 patients (56.9%) exhibited QTc interval prolongation. After follow-up for a median duration of 7.50 days, the QTc interval was 451.79 ± 34.56 ms ( = 0.482), and the number of patients with QTc interval prolongation decreased to 30 (51.7%; = 0.457). The QTc interval normalization rate of patients in the control group with QTc interval prolongation was merely 10.0% (3/33), which was significantly lower than that in the propranolol group ( < 0.001).
CONCLUSION
In patients with cirrhosis complicated by QT interval prolongation, the short-term use of propranolol aids in correction of a long QT interval and provides positive therapeutic value for cirrhotic cardiomyopathy.
PubMed: 38738176
DOI: 10.3389/fphar.2024.1370261 -
Cureus Apr 2024Orbital hemangiomas are benign vascular tumors commonly affecting infants and young children, often manifesting with proptosis, eyelid swelling, or discoloration....
Orbital hemangiomas are benign vascular tumors commonly affecting infants and young children, often manifesting with proptosis, eyelid swelling, or discoloration. Propranolol has emerged as the primary therapy due to its efficacy in promoting regression and minimizing complications. Here, we present a case of a previously healthy six-month-old male infant with progressive right eyelid swelling and discoloration. Magnetic resonance imaging confirmed a large orbital hemangioma. The patient was referred to an ophthalmology center where treatment with propranolol resulted in substantial improvement. Early recognition and initiation of propranolol therapy are crucial in managing orbital hemangiomas in pediatric patients. This case underscores the successful outcome achievable with pharmacologic intervention and emphasizes the importance of long-term follow-up for monitoring and optimizing patient outcomes.
PubMed: 38738043
DOI: 10.7759/cureus.58062 -
Journal of Anxiety Disorders Jun 2024Exposure therapy is an evidence-based treatment option for anxiety-related disorders. Many patients also take medication that could, in principle, affect exposure... (Meta-Analysis)
Meta-Analysis
Exposure therapy is an evidence-based treatment option for anxiety-related disorders. Many patients also take medication that could, in principle, affect exposure therapy efficacy. Clinical and laboratory evidence indeed suggests that benzodiazepines may have detrimental effects. Large clinical trials with propranolol, a common beta-blocker, are currently lacking, but several preclinical studies do indicate impaired establishment of safety memories. Here, we investigated the effects of propranolol given prior to extinction training in 9 rat studies (N = 215) and one human study (N = 72). A Bayesian meta-analysis of our rat studies provided strong evidence against propranolol-induced extinction memory impairment during a drug-free test, and the human study found no significant difference with placebo. Two of the rat studies actually suggested a small beneficial effect of propranolol. Lastly, two rat studies with a benzodiazepine (midazolam) group provided some evidence for a harmful effect on extinction memory, i.e., impaired extinction retention. In conclusion, our midazolam findings are in line with prior literature (i.e., an extinction retention impairment), but this is not the case for the 10 studies with propranolol. Our data thus support caution regarding the use of benzodiazepines during exposure therapy, but argue against a harmful effect of propranolol on extinction learning.
Topics: Propranolol; Animals; Fear; Extinction, Psychological; Rats; Humans; Adrenergic beta-Antagonists; Male; Memory; Midazolam; Adult; Bayes Theorem; Female; Conditioning, Classical; Young Adult
PubMed: 38733644
DOI: 10.1016/j.janxdis.2024.102870 -
Molecules (Basel, Switzerland) May 2024In this study, water was used as an additive in the methanol-modified carbon dioxide-based eluent for the elution of some basic organic compounds from a hybrid silica...
In this study, water was used as an additive in the methanol-modified carbon dioxide-based eluent for the elution of some basic organic compounds from a hybrid silica column via supercritical fluid chromatography (SFC). The experiments were applied to sulfonamides, propranolol, and other organic nitrogen compounds involving aromatic rings from different classes of amine, pyrimidine, and purine with different pKa values (the pKa values for the studied analytes range from 4.6 to 10.4). The results revealed different responses to the different percentages of water addition. Adding 1~2% of water to the modifier (methanol) led to a positive effect manifested by more symmetrical peak shapes and reduced retention times for most compounds. The key factor for this improvement in the properties of chromatographic peaks is due to the adsorption of water on the silanol groups of the stationary phase, consequently resembling the phenomena observed in hydrophilic interaction liquid chromatography (HILIC). Moreover, the availability of hydrogen bond acceptor and donor sites in the analyte structure is an important factor to be considered when adding water as an additive to the modifier for improving the chromatographic peaks. However, introducing water in an amount higher than 3% resulted in perturbed chromatographic signals. It was also found that water as an additive alone could not successfully elute propranolol from the hybrid silica column with an acceptable peak shape; thus, the addition of a strong base such as amine salts was also necessary. The proposed use of a particular amount of water in the mobile phase could have a positive effect compared to the same mobile phase without water, improving the chromatographic peak properties of the elution of some basic organic compounds from the hybrid silica column.
PubMed: 38731614
DOI: 10.3390/molecules29092124 -
American Journal of Translational... 2024To analyze the influence of propranolol (Prop) plus methimazole (MMI) on curative efficacy and thyroid function (TF) of patients with hyperthyroidism (HT).
PURPOSE
To analyze the influence of propranolol (Prop) plus methimazole (MMI) on curative efficacy and thyroid function (TF) of patients with hyperthyroidism (HT).
METHODS
In this retrospective study, 107 cases of HT presented between August 2019 and August 2021 were grouped according to different therapeutic regimens: a control group (the Con) with 53 cases treated with MMI, and a research group (the Res) with 54 cases treated with Prop + MMI. Inter-group comparisons were performed in terms of the following domains: heart rate (HR), efficacy, adverse reactions (ARs), TF parameters (free triiodothyronine, FT3; free thyroxine, FT4; thyroid stimulating hormone, TSH), hepatic function indicators (alanine aminotransferase, ALT; aspartate aminotransferase, AST), and quality of life (Short-Form 36 Item Health Survey, SF-36). Finally, multivariate analysis was performed by Logistic regression to determine the risk factors leading to the ineffectiveness of treatment.
RESULTS
The analysis showed an obviously higher total effective rate and an evidently lower AR rate in the Res compared with the Con group. Besides, the Res group had notably lower FT3, FT4, ALT and AST and statistically higher TSH after treatment compared with the baseline (before treatment) and the Con group. Higher SF-36 scores were also determined in the Res group. Finally, the results of Logistic regression analysis revealed that AST was an independent risk factor for ineffective treatment.
CONCLUSIONS
Prop plus MMI is effective in the treatment of HT, which can effectively improve the HR, thyroid hormone levels, hepatic function, and quality of life of patients, with a lower incidence of ARs.
PubMed: 38715833
DOI: 10.62347/JIYT2536 -
International Medical Case Reports... 2024Idiopathic portal hypertension (IPH) also known as non-cirrhotic portal hypertension is an entity of hepatic conditions including disorders of blood vessels that leads...
PURPOSE
Idiopathic portal hypertension (IPH) also known as non-cirrhotic portal hypertension is an entity of hepatic conditions including disorders of blood vessels that leads to portal hypertension (PHT). Current management of PHT includes medical or endoscopic therapy. A proximal spleno-renal shunt (PSRS) operation has been shown to improve the outcomes of patients with IPH with upper gastrointestinal bleeding refractory to medical and endoscopic therapy in high income countries but the same has not been well described in our resource limited setting.
PATIENTS AND METHODS
This study consecutively included patients who were diagnosed with IPH on pre-operative imaging and underwent PSRS surgery. Data on four patients across the time period of 3 years was obtained with a male to female ratio of 1:1 and age range of 7 to 34 years.
RESULTS
All patients in this study had features of upper gastrointestinal bleeding and, after an endoscopy they were all diagnosed with grade IV esophageal varices. Symptom duration prior to admission varied between 3 months to 8 years. All these patients had multiple episodes of rebleeding varices with recurrent admissions and were managed conservatively by multiple blood transfusions and propranolol tablets, pre-operatively. Only one patient had previous variceal band ligation done though he developed rebleeding. All four patients underwent both PSRS surgery and splenectomy and were intra-operatively verified to have a normal smooth liver and thus IPH was the cause of the esophageal varices. After an average follow-up period of 26.5 months, we found that all patients were alive with early symptomatic relief, no recurrent bleeding and no long-term complications.
CONCLUSION
Good outcomes were achieved in terms of symptom resolution, endoscopic variceal resolution at follow-up endoscopy, length of stay ranging from 8 to 15 days and all four patients were alive at the time of follow-up, that ranged from 14 to 46 months.
PubMed: 38681996
DOI: 10.2147/IMCRJ.S453341 -
Biomedicine & Pharmacotherapy =... Jun 2024Nowadays, there is an increasing emphasis on the need to alleviate the chronic inflammatory response to effectively treat hypertension. However, there are still gaps in...
Nowadays, there is an increasing emphasis on the need to alleviate the chronic inflammatory response to effectively treat hypertension. However, there are still gaps in our understanding on how to achieve this. Therefore, research on interaction of antihypertensive drugs with the immune system is extremely interesting, since their therapeutic effect could partly result from amelioration of hypertension-related inflammation, in which macrophages seem to play a pivotal role. Thus, current comprehensive studies have investigated the impact of repeatedly administered hypotensive drugs (captopril, olmesartan, propranolol, carvedilol, amlodipine, verapamil) on macrophage functions in the innate and adaptive immunity, as well as if drug-induced effects are affected by a high-sodium diet (HSD), one of the key environmental risk factors of hypertension. Although the assayed medications increased the generation of reactive oxygen and nitrogen intermediates by macrophages from standard fed donors, they reversed HSD-induced enhancing effects on macrophage oxidative burst and secretion of pro-inflammatory cytokines. On the other hand, some drugs increased macrophage phagocytic activity and the expression of surface markers involved in antigen presentation, which translated into enhanced macrophage ability to activate B cells for antibody production. Moreover, the assayed medications augmented macrophage function and the effector phase of contact hypersensitivity reaction, but suppressed the sensitization phase of cell-mediated hypersensitivity under HSD conditions. Our current findings contribute to the recognition of mechanisms, by which excessive sodium intake affects macrophage immune activity in hypertensive individuals, and provide evidence that the assayed medications mitigate most of the HSD-induced adverse effects, suggesting their additional protective therapeutic activity.
Topics: Animals; Antihypertensive Agents; Macrophages; Mice; Inflammation; Macrophage Activation; Hypertension; Male; Cytokines; Phagocytosis; Sodium, Dietary; Inflammation Mediators
PubMed: 38677242
DOI: 10.1016/j.biopha.2024.116648 -
Journal of Medical Cases Apr 2024In pediatric-aged patients, hyperthyroidism generally results from the autoimmune disorder, Graves' disease (GD). Excessive levels of thyroid hormones (triiodothyronine...
In pediatric-aged patients, hyperthyroidism generally results from the autoimmune disorder, Graves' disease (GD). Excessive levels of thyroid hormones (triiodothyronine and thyroxine) result in irritability, emotional lability, nervousness, tremors, palpitations, tachycardia, and arrhythmias. The risk of morbidity and mortality is increased when surgical intervention is required in patients with hyperthyroidism due to the potential for the development of thyroid storm (TS). A 3-year, 1-month-old child with a past medical history of GD presented for total thyroidectomy when pharmacologic control with methimazole was not feasible due to intolerance following development of a serum sickness-like illness. Prior to surgery, his thyrotoxicosis symptoms worsened with fever, tachycardia, diaphoresis, and hypertension. He subsequently developed TS and was admitted to the pediatric intensive care unit where management included hydrocortisone, potassium iodide, and β-adrenergic blockade with esmolol and propranolol. Thyroid studies improved prior to surgery, and a total thyroidectomy was successfully completed. Corticosteroid therapy was slowly tapered as an outpatient, and he was discharged home on hospital day 9. Following discharge, his signs and symptoms of thyrotoxicosis resolved, and he was started on oral levothyroxine replacement therapy. The remainder of his postoperative and post-discharge course were unremarkable. Only two case reports of perioperative pediatric TS have been published in the past 20 years. Our case serves as an important reminder of the signs of TS in children and to outline the treatment options in a pediatric patient, especially in those unable to tolerate first-line pharmacologic therapies such as methimazole or propylthiouracil.
PubMed: 38646421
DOI: 10.14740/jmc4197 -
Journal of Ophthalmic & Vision Research 2024Recent studies have reported the promising effect of intravitreal propranolol on retinal neovascularization. However, rapid clearance and short half-life of the drug in...
PURPOSE
Recent studies have reported the promising effect of intravitreal propranolol on retinal neovascularization. However, rapid clearance and short half-life of the drug in the vitreous are the main drawbacks of this therapeutic approach. This study investigates the extension of the residence time of propranolol in the vitreous by polymeric nanoparticles (NPs) with the prospect of improving choroidal neovascularization treatment.
METHODS
The poly (lactic-co-glycolic) acid (PLGA) NPs were fabricated by a modified double emulsion solvent evaporation method and the obtained NPs were characterized for their size, poly dispersity index (PDI), and surface image. The release, cell cytotoxicity, and uptake of NPs were also evaluated. To investigate the effect of the vitreous pharmacokinetic drug loaded NPs versus that of the free propranolol, they were intravitreally injected into the rabbits' eyes and the drug vitreous concentrations in defined intervals were analyzed by high performance liquid chromatography (HPLC).
RESULTS
The spherical NPs with about 230 nm size, and almost 10% drug loading were obtained. Based on the 3-(4, 5-Dimethylthiazol-2-Yl)-2, 5-Diphenyltetrazolium Bromide (MTT) outcomes, 30 µg/ml of propranolol was considered as the guide dosage in the intravitreal injection. Confocal microscopy images verified the presence of labeled NPs in the posterior segment after five days of receiving the injection. assay revealed that the vanishing rate of propranolol in rabbits treated with propranolol NPs was reduced at twice the rate as compared to that of the vanishing rate experienced with only the free drug.
CONCLUSION
PLGA NPs can prolong the existence of propranolol in both vitreous and posterior ocular tissues, and thus, may provide an effective approach in treatment of posterior segment neovascularization.
PubMed: 38638633
DOI: 10.18502/jovr.v19i1.15436