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ABSTRACT Propranolol has been the primary treatment for infantile hemangioma (IH) since 2008. Prior studies have investigated the effects in late childhood of propranolol therapy given in infancy for IH, including neurocognitive dysfunction, sleep disorders, and hypoglycemia. However, few studies have determined the risk of these adverse effects later in life. Using the TrinetX database, we studied the risk of growth impairment, sleep disorders, learning disabilities, and diabetes mellitus in children aged 10–17 years who had received propranolol for IH in infancy. The maximum age of 17 years was chosen for the study, as propranolol was established as a treatment for IH in 2008. The results showed no statistically significant risk of growth impairment, sleep disorders, learning disabilities, or diabetes mellitus in IH patients treated with propranolol. These findings support existing evidence that propranolol therapy given in infancy for IH is not associated with long‐term adverse effects up to age 17 years in the studied patient population. [ABSTRACT FROM AUTHOR]

Background: Essential tremor (ET) is a chronic, progressive neurological disease that affects an estimated 7 million individuals in the United States (ie, 2.2% of the entire U.S. population). Despite its high prevalence, there are a few published studies on patterns of prescription medication use among patients. Objective: The aim was to examine prescription drug medication use among ET patients. Methods: This is a cross‐sectional study of ET patients, age ≥40, with at least 1 prescription medication fill using the Optum's de‐identified Clinformatics Data Mart Database from 2018 through 2019. We examined patterns of fills of key agents used to treat ET. Results: The final sample comprised 36,839 ET patients in the United States; 89% had at least 1 prescription drug claim over a 2‐year period, indicating that 9 of 10 ET patients take a medication to treat their disease. For each of the 3 most frequently prescribed medications, only a modest fraction (1/5 to 1/4) of patients were taking that medication. Adherence to these agents was 52% to 61%. A high percentage of patients had fills for more than 1 of the main agents we studied. Conclusion: These data illustrate a need for medication in the ET population. There is only 1 FDA‐approved medication to treat ET, propranolol, and less than 25% of ET patients used this drug during our study period. At the same time, no single agent was utilized by more than one quarter of ET patients, adherence was low, and use of multiple agents was common. For such a common disease, the pharmacotherapeutic landscape is impoverished. [ABSTRACT FROM AUTHOR]

Contrasting with the lymphopenia classically reported after administration of glucocorticoids, a lymphocytosis has been sometimes observed in patients after glucocorticoid administration. We here determine prospectively the timing and magnitude of methylprednisolone (mPDN)-induced lymphocytosis and study the effects of concomitant propranolol administration on lymphocyte count (Ly). Ly was measured before and 24 to 72 hours after initiating mPDN treatment in 20 patients with immune-mediated inflammatory disorders (IMID). After one week, patients with increased Ly were divided in two groups receiving, in addition to mPDN, either propranolol or a placebo; Ly was determined 4 days later. Lymphocyte subpopulations and mPDN plasma levels were determined in subsets of the patients. Values are expressed as median with 25%–75% interquartile range. A 73.4% (37–305) increase of Ly was observed in 18/20 patients as soon as 48 (48–72) hours after initiating mPDN (32 mg; 16–32). Lymphocytosis (Ly ≥ 4000/μL) was observed in 7 patients and hyperlymphocytosis (Ly ≥ 5000/μL) in 4 of them. The increase in Ly was noted both for B and T cells. Median mPDN plasma levels (n = 13) were 97.4 ng/mL (IQR 67–489) and 3.2 (IQR 2.1–5.1) respectively 8 hours and 24 hours after oral mPDN administration. No significant change in Ly was shown under propranolol (p = 0.570). A morning lymphocytosis observed during mPDN treatment occurs in the very first days of mPDN administration. Our results do not support the hypothesis of an increased adrenergic tone responsible for this phenomenon. Identifying this unexpected etiology of lymphocytosis could mitigate the need for unnecessary supplementary investigations in clinical practice. [ABSTRACT FROM AUTHOR]

Atenolol is a commonly used beta bloscker in non-pregnant women. Many providers are hesitant in prescribing atenolol in pregnancy because of a possible association with poor fetal growth. We aimed to assess the association between atenolol and the occurrence of small for gestational age neonates compared to other beta blockers, as described in the existing literature. We used the meta-analytic method to generate a forest plot for risk ratios (RR) of small for gestational age in patients who used atenolol vs. other beta blockers. Statistical heterogeneity was assessed with the I2 statistic. Two studies were included, with a resultant RR of 1.94 [95 % confidence interval (CI) 1.60; 2.35]. A study by Duan et al. in 2018 noted the following rate of small for gestational age for each beta blocker use: 112/638 atenolol, 590/3,357 labetalol, 35/324 metoprolol, and 50/489 propranolol. A study by Tanaka et al. in 2016 noted the following rate of small for gestational age: 8/22 for propranolol, 2/12 for metoprolol, 2/6 for atenolol, 0/5 for bisoprolol. Heterogeneity (I2) was 0 %. Our results suggested an elevated risk of small for gestational age associated with atenolol use in comparison to other beta blockers, specifically labetalol, propranolol, bisoprolol, and metoprolol. [ABSTRACT FROM AUTHOR]

Severe burn injuries are defined by a prolonged hypermetabolic response characterized by increases in resting energy expenditure, systemic catabolism, and multi-organ dysfunction. The sustained elevation of catecholamines following a burn injury is thought to significantly contribute to this hypermetabolic response, leading to changes in adipose tissue such as increased lipolysis and the browning of subcutaneous white adipose tissue (WAT). Failure to mitigate these adverse changes within the adipose tissue has been shown to exacerbate the post-burn hypermetabolic response and lead to negative outcomes. Propranolol, a non-selective β-blocker, has been clinically administered to improve outcomes of pediatric and adult burn patients, but there is inadequate knowledge of its effects on the distinct adipose tissue depots. In this study, we investigated the adipose depot-specific alterations that occur in response to burn injury. Moreover, we explored the therapeutic effects of β-adrenoceptor blockade via the drug propranolol in attenuating these burn-induced pathophysiological changes within the different fat depots. Using a murine model of thermal injury, we show that burn injury induces endoplasmic reticulum (ER) stress in the epididymal (eWAT) but not in the inguinal (iWAT) WAT depot. Conversely, burn injury induces the activation of key lipolytic pathways in both eWAT and iWAT depots. Treatment of burn mice with propranolol effectively mitigated adverse burn-induced alterations in the adipose by alleviating ER stress in the eWAT and reducing lipolysis in both depots. Furthermore, propranolol treatment in post-burn mice attenuated UCP1-mediated subcutaneous WAT browning following injury. Overall, our findings suggest that propranolol serves as an effective therapeutic intervention to mitigate the adverse changes induced by burn injury, including ER stress, lipotoxicity, and WAT browning, in both adipose tissue depots. Key messages: Burn injury adversely affects adipose tissue metabolism via distinct changes in both visceral and subcutaneous adipose depots. Propranolol, a non-selective β-adrenergic blocker, attenuates many of the adverse adipose tissue changes mediated by burn injury. [ABSTRACT FROM AUTHOR]

Objective(s): In the present study, the relaxant effect of crocetin on tracheal smooth muscle cells (TSM) and its possible mechanisms were evaluated. Materials and Methods: The study was conducted on 54 male Wistar rats in 8 groups. TSM was contracted by methacholine (10 μM) and KCl (60 mM), and the relaxant effects of four cumulative concentrations of crocetin, petal extract of saffron, and theophylline were examined on non-incubated and TSM incubated with propranolol, chlorpheniramine, diltiazem, atropine, glibenclamide, and indomethacin were investigated. Results: In non-incubated TSM contracted by methacholine or KCl, crocetin and theophylline showed concentration-dependent relaxant effects (all, P<0.001). However, various concentrations of crocetin showed significantly lower relaxant effects compared to those of theophylline (all, P<0.001). In the methacholine-induced contraction of TSM, the relaxation effect of the last concentration of crocetin in the TSM incubated with propranolol was lower than in non-incubated TSM (P<0.05). In the incubated TSM with chlorpheniramine, the relaxant effects of the two last concentrations of crocetin were significantly lower than in the non-incubated tissues contracted by KCl (P<0.05 and P<0.0). The levels of EC50 crocetin in the incubated TSM with glibenclamide, chlorpheniramine, and indomethacin were markedly lower than in non-incubated (all, P<0.05). Conclusion: The results showed potent relaxation effects of crocetin on TSM and were suggested to be through stimulation of ß-adrenergic receptors, inhibition of histamine (H1 ) receptors, and potassium channel opening mechanisms. [ABSTRACT FROM AUTHOR]

Background: Obstructive sleep apnea (OSA), characterized by chronic intermittent hypoxia (CIH), is a prevalent condition that has been associated with various forms of cancer. Although some clinical studies suggest a potential link between OSA and lung cancer, this association remains uncertain, and the underlying mechanisms are not fully understood. This study investigated the role of the catecholamine-β-adrenergic receptor (βAR) and the NLRP3 inflammasome in mediating the effects of CIH on lung cancer progression in mice. Methods: Male C57BL/6 N mice were subjected to CIH for four weeks, with Lewis lung carcinoma cells seeded subcutaneously. Propranolol (a βAR blocker) or nepicastat (an inhibitor of catecholamine production) was administered during this period. Tumor volume and tail artery blood pressure were monitored. Immunohistochemical staining and immunofluorescence staining were employed to assess protein expression of Ki-67, CD31, VEGFR2, PD-1, PD-L1, and ASC specks in tumor tissues. ELISA was used to detect catecholamine and various cytokines, while western blot assessed the expression of cyclin D1, caspase-1, and IL-1β. In vitro tube formation assay investigated angiogenesis. NLRP3 knockout mice were used to determine the mechanism of NLRP3 in CIH. Results: CIH led to an increase in catecholamine. Catecholamine-βAR inhibitor drugs prevented the increase in blood pressure caused by CIH. Notably, the drugs inhibited CIH-induced murine lung tumor growth, and the expression of Ki-67, cyclin D1, CD31, VEGFR2, PD-1 and PD-L1 in tumor decreased. In vitro, propranolol inhibits tube formation induced by CIH mouse serum. Moreover, CIH led to an increase in TNF-α, IL-6, IL-1β, IFN-γ and sPD-L1 levels and a decrease in IL-10 in peripheral blood, accompanied by activation of NLRP3 inflammasomes in tumor, but these effects were also stopped by drugs. In NLRP3-knockout mice, CIH-induced upregulation of PD-1/PD-L1 in tumor was inhibited. Conclusions: Our study underscores the significant contribution of β-adrenergic signaling and the NLRP3 inflammasome to CIH-induced lung cancer progression. These pathways represent potential therapeutic targets for mitigating the impact of OSA on lung cancer. [ABSTRACT FROM AUTHOR]

While ulceration is one of the most common infantile hemangioma (IH) complications, severe bleeding is a rare consequence, with a paucity of patients reported. We report a 5‐month‐old girl with a very large, mixed, partial segmental IH of the upper chest wall who, despite medical intervention, developed severe ulceration and multiple episodes of life‐threatening bleeding that ultimately led to hemorrhagic shock. Experience in our patient and a review of six previous reports shows that severe bleeding is a risk when ulceration extends directly into an arterial feeding vessel that is often visible clinically. Other potential predictors for severe bleeding include large to very large IH size with extension of the tumor into underlying structures, segmental or partial segmental patterning, mixed and bulky morphology, and white discoloration as a sign of impending or worsening ulceration. [ABSTRACT FROM AUTHOR]

Objective: The efficacy and safety of propranolol for retinopathy of prematurity (ROP) remain under debate. This network meta-analysis (NMA) focuses on whether a ranking may be established for different dose levels of propranolol as treatment of ROP in terms of stage progression as the primary outcome, with appearance of plus disease and need for anti-vascular endothelial growth factors (anti-VEGFs) or laser therapy as secondary endpoints. Methods: Fourteen studies (10 randomised controlled trials, three single-arm trials and one retrospective observational study) of 474 patients treated with oral or ocular propranolol were retrieved from databases up to April 2024. Meta-insight and model-based NMA were undertaken to evaluate the propranolol dose–response relationship. Studies were evaluated for model fit, risk of bias and Confidence of evidence In Network Meta-Analysis (CINeMA). Effect sizes were determined as odds ratio (OR) with 95% credible interval (CrI). Results: Bayesian analysis showed a trend towards improved effects for propranolol given at late stages (stages 2–3; S23) of ROP progression compared with its administration at earlier stages (stages 0–1; S01). OR values for oral propranolol 1.5 and 2 mg/kg/day given at S23 were 0.13 (95% CrI 0.04–0.37) and 0.16 (95% CrI 0.04–0.61), respectively, while given at S01 were 0.28 (95% CrI 0.02–2.96) and 0.78 (95% CrI 0.14–4.43), respectively. Similarly, OR of eye propranolol 0.2% at S23 was 0.37 (95% CrI 0.09–1.00) versus an S01 OR of 0.64 (95% CrI 0.21–2.04). Surface under the cumulative ranking curve (SUCRA) analyses confirmed best probability values for oral propranolol 1.5–2 mg/kg followed by eye propranolol 0.2%, all at S23. Model-based NMA showed nonlinearity in the dose–response for oral propranolol with a trend to greater maximal effect for its administration at late versus early stages. For secondary endpoints, lower risk values were found with oral propranolol 1.5 mg/kg/day at S23 for progression to plus disease (OR 0.14; 95% CrI 0.02–0.84) and need for anti-VEGFs (OR 0.23; 95% CrI 0.05–0.93) and laser (OR 0.16; 95% CrI 0.02–1.10) therapies also followed by eye propranolol 0.2%, and a similar profile was obtained with SUCRA analysis. Lower doses (0.5–1.0 mg/kg/day) of oral propranolol retained efficacy. Threat of adverse events was estimated as risk difference versus control with no difference for eye propranolol 0.2% and oral propranolol 0.5 mg/kg/day, modest increases of risk for oral propranolol 1.0 and 1.5 mg/kg/day and the highest risk difference for oral propranolol 2.0 mg/kg/day (0.06; 95% CI −0.01 to 0.13). Conclusion: A diminished risk of disease progression and need for additional treatment was obtained with propranolol in ROP, but safety is a potential concern. Propranolol eye micro-drops (0.2%) can be as efficacious as oral propranolol. Nonetheless, the evidence is limited due to the paucity and quality of the available studies. [ABSTRACT FROM AUTHOR]

The aim of the current study was to fabricate and optimize solid lipid nanoparticles (SLNs) loaded topical hydrogel for the treatment of infantile hemangioma (IH). Propranolol is used to treat IH; however, its systemic use has several worsening side effects in infants. To cope with this problem, a novel topical formulation was designed. Firstly, propranolol was desalted, and Precirol solid lipid nanoparticles (SLNs) were fabricated by utilizing hot emulsion technique. The response surface methodology was used for optimization of nanoparticles. The optimized nanoformulation was characterized for its particle diameter, zeta potential, surface morphology, entrapment efficiency, crystallinity, and molecular interaction. Afterwards, these nanoparticles were loaded into Carbopol hydrogel for topical drug delivery. In vitro release and ex vivo permeation studies were also conducted to gauge the potential of SLNs loaded hydrogel. The optimized formulation exhibited particle size of approximately 130 nm with PDI of 0.232 and zeta potential of − 22.9 mV. Crystallinity studies and Fourier transform infrared (FTIR) analysis revealed no molecular interaction. This novel hydrogel can play a crucial role in controlling the IH in neonates. [ABSTRACT FROM AUTHOR]

Summary: Purpose: Multiple Myeloma (MM) is considered an incurable, biologically heterogeneous disease of the plasma cells. The clinical data on the association between stress and the molecular mechanism of stress hormone receptor expression and its relationship with IL‑6 signaling pathway have not yet proposed a clear answer in MM. This study aims to explore the effect of isoproterenol and propranolol, which are beta-adrenergic agonists and antagonists, respectively on suppressor of cytokine signaling (SOCS) and IL-6/gp130 signaling in MM cell lines. Material and methods: Four different MM cell lines (KMM‑1, RPMI 8226, LP‑1, and L363) were treated with isoproterenol and propranolol. Optimal dosages of isoproterenol and propranolol were determined, and the mRNA expression levels of IL‑6, gp130, and SOCS‑1 were examined using qRT-PCR. Results: The analysis of our results indicated that propranolol, as a β-adrenoreceptor antagonist, could increase MM cell death and ameliorate IL‑6 and its receptor gp130 in addition to up-regulate SOCS‑1 gene expression. On the other hand, isoproterenol, as a β-adrenoreceptor agonist, could provoke MM cell viability and IL‑6 expression. Conclusions: β‑adrenergic signaling seems to affect cell viability through targeting IL-6/gp130 and SOCS‑1 signaling in MM, underscoring the importance of further studies on stress hormones and IL‑6 suppressors as potent candidates for MM therapy. [ABSTRACT FROM AUTHOR]

Background: Infantile haemangiomas (IHs) sometimes require treatment with propranolol. Sleep disturbances are the most frequently reported side effects. Monitoring adverse drug events necessitates repeated hospital visits, which can be challenging during a pandemic. Objectives: To explore the effectiveness of a new electronic questionnaire in identifying sleep disturbances related to treatment with propranolol and potential confounding factors. To evaluate the response rate to the questionnaire. To report the proportion of patients on propranolol with sleep disturbances. Methods: In an observational, prospective cohort study, caregivers provided clinical information during ambulatory visits and via an electronic questionnaire after an 8-week treatment course with propranolol and at the time of treatment interruption. Adverse drug reaction reporting forms were assessed for causality. Results: The questionnaire response rate was 91%, and the completion rate was 100%. A total of 59% of patients experienced sleep disturbances during propranolol treatment, which were considered adverse reactions. Sleep disorders were frequent during sleep regression phases and in subjects who fell asleep during physical contact with caregivers or bed-sharing with parents. Conclusion: The application of this questionnaire allows for identifying adverse sleep events associated with propranolol in IHs and potential confounders. Counselling on sleep hygiene is recommended before treatment onset. [ABSTRACT FROM AUTHOR]

This research investigated the adsorption of propranolol (PROP) by functionalized green carbon nanotubes (MWCNT-B), assessing the influence of pH, in addition to kinetic, equilibrium, and thermodynamic studies and reuse of the material. For this purpose, speciation of PROP and the point of zero charge (pHPZC) of MWCNT-B were performed, indicating a pKa of 9.67 and pHPZC of 3.31. The adsorption tests at different pH values revealed that in the range of pH 3 to 9, there is no significant variation in PROP uptake, despite this, at pH 11, the removal decreases. Regarding PROP adsorption, the equilibrium time ranged from 30 to 90 min, and the PFO model best represented the kinetic data. The Langmuir model was more predictive in representing isotherms (R2 > 0.95), and the adsorption process was spontaneous and favorable (ΔG < − 20 kJ mol−1) and indicated exothermic behavior (ΔH = − 33 kJ mol−1) for PROP removal. In addition, the material showed satisfactory thermal regeneration results and can be reused for four cycles. The results suggest that MWCNT-B is an attractive adsorbent and exhibits effective removal of propranolol from aqueous matrices. [ABSTRACT FROM AUTHOR]