Nonselective Beta-adrenergic Antagonist Research Articles

Novel Properties of Old Propranolol-Assessment of Antiglycation Activity through In Vitro and In Silico Approaches.

Hypertension has earned the "silent killer" nickname since it may lead to a number of comorbidities, including diabetes and cardiovascular diseases. Oxidative stress and protein glycation play vital roles in the pathogenesis of hypertension. Several studies have shown that they profoundly account for vascular dysfunction, endothelial damage, and disruption of blood pressure regulatory mechanisms. Of particular note are advanced glycation end products (AGEs). AGEs alter vascular tissues' functional and mechanical properties by binding to receptors for advanced glycation end products (RAGE), stimulating inflammation and free radical-mediated pathways. Propranolol, a nonselective beta-adrenergic receptor antagonist, is one of the most commonly used drugs to treat hypertension and cardiovascular diseases. Our study is the first to analyze propranolol's effects on protein glycoxidation through in vitro and in silico approaches. Bovine serum albumin (BSA) was utilized to evaluate glycoxidation inhibition by propranolol. Propranolol (1 mM) and BSA (0.09 mM) were incubated with different glycating (0.5 M glucose, fructose, and galactose for 6 days and 2.5 mM glyoxal and methylglyoxal for 12 h) or oxidizing agents (chloramine T for 1 h). Biomarkers of protein glycation (Amadori products (APs), β-amyloid (βA), and advanced glycation end products (AGEs)), protein glycoxidation (dityrosine (DT), kynurenine (KYN), and N-formylkynurenine (NFK)), protein oxidation (protein carbonyls (PCs), and advanced oxidation protein products (AOPPs)) were measured by means of colorimetric and fluorimetric methods. The scavenging of reactive oxygen species (hydrogen peroxide, hydroxyl radical, and nitric oxide) and the antioxidant capacity (2,2-diphenyl-1-picrylhydrazyl radical and ferrous ion chelating (FIC) assays)) of propranolol were also evaluated. Additionally, in silico docking was performed to showcase propranolol's interaction with BSA, glycosides, and AGE/RAGE pathway proteins. The products of protein glycation (↓APs, ↓βA, ↓AGEs), glycoxidation (↓DT, ↓KYN, ↓NFK), and oxidation (↓PCs, ↓AOPPs) prominently decreased in the BSA samples with both glycating/oxidizing factors and propranolol. The antiglycoxidant properties of propranolol were similar to those of aminoguanidine, a known protein oxidation inhibitor, and captopril, which is an established antioxidant. Propranolol showed a potent antioxidant activity in the FIC and H2O2 scavenging assays, comparable to aminoguanidine and captopril. In silico analysis indicated propranolol's antiglycative properties during its interaction with BSA, glycosidases, and AGE/RAGE pathway proteins. Our results confirm that propranolol may decrease protein oxidation and glycoxidation in vitro. Additional studies on human and animal models are vital for in vivo verification of propranolol's antiglycation activity, as this discovery might hold the key to the prevention of diabetic complications among cardiology-burdened patients.

Cardiac Evaluation before and after Oral Propranolol Treatment for Infantile Hemangiomas.

Background: Most recent clinical practice guidelines addressing the management of infantile hemangiomas (IHs) recommend oral propranolol, a non-selective beta-adrenergic antagonist, as first-line treatment. However, few reports have provided continuous follow-up data regarding cardiac evaluations. Methods: Sixty-four patients diagnosed with IHs and treated with oral propranolol before 2 years of age at the Department of Pediatrics, Kangbuk Samsung Hospital (Seoul, Republic of Korea), with regular examinations between 2017 and 2021, were included. Cardiac evaluations, including electrocardiography, Holter monitoring, chest X-ray, and echocardiography, were performed. Results: Sixty-four patients with IHs successfully underwent continuous follow-up cardiac evaluations. The median age at diagnosis was 2 weeks (1 day to 34.3 weeks). The median age at treatment initiation was 13.6 weeks (2.4-87.9 weeks), the mean longitudinal diameter of hemangioma at diagnosis was 2.8 ± 2.1 cm (0.3-12.0 cm), and the mean percentage of size decrease after 1 year of oral propranolol treatment was 71.8%. None of the 64 patients experienced severe adverse side effects during propranolol treatment. There was no statistically significant differences in echocardiographic function and electrocardiographic data after treatment. Conclusions: Propranolol treatment ≥6 months was effective and safe without significant cardiac toxicity in the treatment of patients with infantile hemangiomas.

Comprehensive Characterization and Comparative Assessment of Carvedilol Solid Dispersions: Insights into Enhanced Bioavailability and Stability Profiles

Carvedilol, a non-selective beta-adrenergic antagonist, poses a challenge in achieving optimal bioavailability due to its poor aqueous solubility. This study aimed to enhance the solubility and dissolution rate of carvedilol through the formulation and evaluation of solid dispersions. Various solid dispersion formulations were prepared using different carriers and methods, including solvent evaporation, fusion, and spray-drying techniques. The prepared formulations were systematically characterized using Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and scanning electron microscopy (SEM) to investigate drug-carrier interactions, solid-state changes, and morphological characteristics. Evaluation of the formulated solid dispersions involved in vitro dissolution studies, solubility enhancement assays, and stability assessments. Dissolution profiles revealed significantly improved drug release rates for the solid dispersion formulations compared to the pure drug. The solubility of carvedilol was notably enhanced in the solid dispersion systems, indicating improved drug dissolution behavior. Stability studies demonstrated the robustness of selected formulations against environmental factors over an extended period. Moreover, pharmacokinetic studies conducted in animal models showcased enhanced bioavailability of carvedilol from the optimized solid dispersion formulation compared to the conventional drug formulation. This comprehensive investigation provides valuable insights into the development of carvedilol solid dispersions, elucidating the influence of formulation variables on drug solubility, dissolution, stability, and ultimately, bioavailability enhancement. The findings underscore the potential of solid dispersion technology as a promising strategy to overcome the solubility challenges associated with carvedilol, paving the way for improved therapeutic efficacy and patient compliance.

Clinical pharmacokinetics of nadolol: A systematic review.

Nadolol is a non-selective beta-adrenergic antagonist that is used for the treatment of hypertension and angina. The primary route for its administration is oral. It is given once daily as it has a longer half-life (t½). The purpose of conducting this systematic review is to provide a comprehensive view of all the available pharmacokinetic (PK) data on nadolol in humans. This review aimed to systematically collate and analyze publish data on the clinical PK of nadolol in humans and this can be beneficial for the clinicians in dosage adjustments. Two electronic databases PubMed and Google Scholar were used for conducting a systematic literature search. All the relevant articles containing PK data of nadolol in humans were retrieved. A total of 1275 articles were searched from both databases and after applying eligibility criteria finally, 22 articles were included for conducting the systematic review. The area under the plasma concentration curve (AUC) and maximum plasma concentration (Cmax ) of nadolol increased in a dose-dependent manner. The t½ of nadolol was increased to double (18.2-68.6 h) in the patients with chronic kidney disease while the serum t½ became shorter (3.2-4.3 h) when administered to the children. The bioavailability of nadolol was greatly reduced by the coadministration of green tea. Nadolol can be effectively removed by hemodialysis. It undergoes enterohepatic circulation thus activated charcoal decreased its bioavailability. Since, there is no previous report of a systematic review on the PK of nadolol, the current review encompasses all the relevant published articles on nadolol in humans. The analysis and understanding of PK parameters (AUC, Cmax , and t½) of nadolol may be helpful in the development and evaluation of PK models.

Development and In-Vitro Evaluation of Plantago ovata Based Rapid Disintegrating Tablets of Labetalol Hydrochloride

Objectives: To avoid swallowing problems of conventional tablets and improved patient compliance Plantago Ovata based Labetalol HCl Rapid disintegrating tablets have been prepared. Methods: Six different (F1 to F6) batches of Labetalol HCl Rapid disintegrating tablets were developed by ‘direct compression method’ using Plantago ovata as a natural super-disintegrating agent. The formulated RDT were tested for angle of repose’, densities like tapped and bulk density, Hausner’s ratio, Carr’s index like pre-compression parameters and for thickness, weight variation or weight uniformity, tablet hardness, % drug content or content uniformity, water absorption ratio’, time require for wetting of tablets’ means wetting time, in-vitro drug disintegration time and in-vitro drug dissolution studies under post-compression parameters of evaluation. Results: It was found that the all the results of these pre-compression and post-compression parameters comply with official standards. The drug release was determined using dissolution media of pH 6.8 phosphate buffer through in-vitro dissolution of drug. This study showed that a rapid drug release by prepared tablets. The optimized formulation F6 showed higher water absorption ratio`, lower wetting time, minimum in-vitro disintegration time’ and higher drug release amongst all the formulations. The F6 formulation was considered the best among all formulations. Conclusion: The prepared rapid disintegrating tablets shows rapid onset of action by quick drug release, minimize side effects and enhanced patient compliance. These prepared tablets containing selective alpha-1 and non-selective beta adrenergic antagonist’ drug candidate Labetalol HCl, will be very useful in the treatment of high blood pressure with enhanced bioavailability.
 Keywords: Rapid disintegrating tablets, Labetalol Hydrochloride, Bioavailability Enhancement, Natural Superdisintegrant, Plantago Ovata, High Blood Pressure, RDT, Patient Compliance

Update on infantile hemangioma.

The International Society for the Study of Vascular Anomalies classifies vascular anomalies into vascular tumors and vascular malformations. Vascular tumors are neoplasms of endothelial cells, among which infantile hemangiomas (IHs) are the most common, occurring in 5%–10% of infants. Glucose transporter-1 protein expression in IHs differs from that of other vascular tumors or vascular malformations. IHs are not present at birth but are usually diagnosed at 1 week to 1 month of age, rapidly proliferate between 1 and 3 months of age, mostly complete proliferation by 5 months of age, and then slowly involute to the adipose or fibrous tissue. Approximately 10% of IH cases require early treatment. The 2019 American Academy of Pediatrics clinical practice guideline for the management of IHs recommends that primary care clinicians frequently monitor infants with IHs, educate the parents about the clinical course, and refer infants with high-risk IH to IH specialists ideally at 1 month of age. High-risk IHs include those with life-threatening complications, functional impairment, ulceration, associated structural anomalies, or disfigurement. In Korea, IHs are usually treated by pediatric hematology-oncologists with the cooperation of pediatric cardiologists, radiologists, dermatologists, and plastic surgeons. Oral propranolol, a nonselective beta-adrenergic antagonist, is the first-line treatment for IHs at a dosage of 2–3 mg/kg/day divided into 2 daily doses maintained for at least 6 months and often continuing until 12 months of age. Topical timolol maleate solution, a topical nonselective beta-blocker, may be used for small superficial type IHs at a dosage of 1–2 drops of 0.5% gel-forming ophthalmic solution applied twice daily. Pulse-dye laser therapy or surgery is useful for the treatment of residual skin changes after IH involution.

Propranolol for Induction of Labor in Nulliparas trial a double-blind, randomized, placebo-controlled trial

Propranolol hydrochloride is a nonselective beta-adrenergic antagonist that has a known activity in the myometrium. Small trials have shown that propranolol decreases the duration of induced labor, although those studies are limited by methodological variability. Our objective was to determine whether the addition of a single dose of propranolol to induce labor in nulliparous women would decrease total time to vaginal delivery. This study was a double-blind, randomized, placebo-controlled trial of nulliparous patients undergoing term induction of labor with a singleton, nonanomalous gestation. Subjects were randomized to 2 mg of intravenous propranolol hydrochloride or an identical-appearing saline placebo, administered 30 minutes after starting the induction of labor. Investigators, labor floor staff, and patients were blinded to the study drug allocation. The primary outcome was time to vaginal delivery. Secondary outcomes included mode of delivery, duration of the phases of labor, time to full dilation, composite maternal morbidity, and composite neonatal morbidity. Data were analyzed by intention-to-treat analysis with a P value of ≤.05 considered significant. In this study, 240 patients were enrolled from December 2017 to December 2018, with 121 patients randomized to the propranolol group and 119 to the placebo group. The 2 groups had similar baseline characteristics. Of the patients randomized, 154 (64.2%) delivered vaginally. There was no significant difference in time from the start of the induction of labor to vaginal delivery (13.8±5.4 hours for propranolol vs 14.3±5.3 hours for placebo; P=.58). There was also no difference in the rate of cesarean delivery (38% vs 33.6%; P=.48), time to active labor (11.0±5.0 vs 11.2±4.5 hours; P=.77), or time to full dilation (12.4±5.1 vs 12.8±5.2 hours; P=.60) in patients receiving propranolol compared with those receiving placebo. Subjects randomized to the propranolol group had a significantly lower rate of composite maternal morbidity (28.9% vs 41.2%; risk ratio, 0.70; 95% confidence interval, 0.49-1.00; P=.047). Rates of postpartum hemorrhage (12.4% vs 21.8%; P=.05) and transfusion (0% vs 4.2%; P=.03) were also lower in the treated group. There was no significant difference in neonatal outcomes or composite morbidity (risk ratio, 0.74; 95% confidence interval, 0.44-1.22). In this study, there is no evidence that the addition of a 1-time dose of propranolol to induce labor in nulliparous women decreases time to delivery or the rate of cesarean delivery. However, propranolol significantly reduced composite maternal morbidity without adverse neonatal effects.

Treatment of Antipsychotic-Induced Akathisia: Role of Serotonin 5-HT2a Receptor Antagonists

Akathisia is one of the most prevalent and distressing adverse effects associated with antipsychotic drug treatment. Propranolol, a non-selective beta-adrenergic receptor antagonist, is currently considered a first-line treatment for antipsychotic-induced akathisia (AIA). Surprisingly, the evidence for its anti-akathisia effect is modest. Propranolol's side effects (e.g. orthostatic hypotension, bradycardia), contraindications (e.g. asthma) and increased complexity in titration schedules limit its use in some patients. Anticholinergic agents and benzodiazepines merely provide symptomatic relief in patients with AIA. Effective and well-tolerated treatment remains a major unmet need in akathisia and warrants a search for new anti-akathisia agents. Accumulating evidence during the last two decades indicates that agents with marked postsynaptic serotonin 5-HT2a receptor antagonism (ritanserin, cyproheptadine, trazodone, mianserin, mirtazapine) may represent a new class of potential anti-akathisia remedies. Among these agents, low-dose mirtazapine (7.5mg or 15mg once daily) has demonstrated the most compelling evidence for therapeutic efficacy. In this narrative review we highlight the clinical significance of AIA, outline major approaches for its management and propose a practical algorithm for its treatment.

Efficacy and safety of propranolol for treatment of temporomandibular disorder pain: a randomized, placebo-controlled clinical trial.

Propranolol is a nonselective beta-adrenergic receptor antagonist. A multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 2b trial enrolled participants aged 18 to 65 years with temporomandibular disorder myalgia to evaluate efficacy and safety of propranolol compared with placebo in reducing facial pain. Participants were randomized 1:1 to either extended-release propranolol hydrochloride (60 mg, BID) or placebo. The primary endpoint was change in facial pain index (FPI = facial pain intensity multiplied by facial pain duration, divided by 100). Efficacy was analyzed as a mean change in FPI from randomization to week 9 and as the proportion of participants with ≥30% or ≥50% reductions in FPI at week 9. Regression models tested for treatment-group differences adjusting for study site, sex, race, and FPI at randomization. Of 299 participants screened, 200 were randomized; 199 had at least one postrandomization FPI measurement and were included in intention-to-treat analysis. At week 9, model-adjusted reductions in mean FPI did not differ significantly between treatment groups (-1.8, 95% CL: -6.2, 2.6; P = 0.41). However, the proportion with a ≥30% reduction in FPI was significantly greater for propranolol (69.0%) than placebo (52.6%), and the associated number-needed-to-treat was 6.1 (P = 0.03). Propranolol was likewise efficacious for a ≥50% reduction in FPI (number-needed-to-treat = 6.1, P = 0.03). Adverse event rates were similar between treatment groups, except for more frequent fatigue, dizziness, and sleep disorder in the propranolol group. Propranolol was not different from placebo in reducing mean FPI but was efficacious in achieving ≥30% and ≥50% FPI reductions after 9 weeks of treatment among temporomandibular disorder participants.

Development and investigation of timolol maleate niosomal formulations for the treatment of glaucoma

The objective of the present study was to develop niosomal gels loaded with Timolol Maleate (TM), Non-selective beta-adrenergic receptor antagonist, for prolonged duration and improved bioavailability for glaucoma treatment. TM niosomes were prepared by film hydration method with various mixtures of different non-ionic surfactants including Span 20, 40, 60 and Tween 20, 40, along with cholesterol. The prepared vesicles were evaluated for entrapment efficiency, in vitro drug release, particle size, zeta potential and morphology by optical and transmission electron microscopy (TEM). The selected formulations were incorporated into Sodium carboxymethyl cellulose (CMC Na) and Carbopol 934 gels. Gel formulations were characterized for in vitro drug permeation and ex vivo drug permeation through bovine cornea. In addition, stability study, isotonicity test and in-vivo evaluation of the selected formulations were done. The results showed that, the niosomes formed were white and spherical in shape with uniform particle size. Formulations containing span 60 and that containing mixture of span 60 and tween 40 gave the highest entrapment efficiency (94.6% and 98.8%, respectively) and a sustained release of timolol maleate from the niosomes within 24 h (96% and 97.10%, respectively). The in vitro and ex vivo drug release studies showed that there was a slow and prolonged release of drug from niosomal gel formulations. Considering the in-vitro release, niosomal gel formulae GN5 and GN6 (containing CMC Na 3% w/w) were the best among the studied formulations. Draize test was carried out and the intra-ocular pressure lowering activity of prepared formulations were detected and compared with marketed Timogel. Formula containing 3% CMC Na showed relative bioavailability 1.6 times more than bioavailability of marketed Timogel.

Local Application of Propranolol and Treatment of Diabetic Vulovagnitis

Background: Propranolol (PRO) is a commonly used non-selective beta-adrenergic receptor antagonist used in the treatment of hypertension, angina, anxiety, cardiac arrhythmia, hyperthyroidism, essential tremor and as a prophylaxis against migraine, variceal bleeding and myocardial infarction diabetes mellitus (T2DM) is a debilitating disease with multiple complications resulting from hyperglycemia, inflammation, and possibly immune dysfunction. It is well established that yeasts thrive in a sugar-rich environment, and therefore, it is logical to hypothesize that high glucose concentrations in patients with diabetes may be responsible for promoting the occurrence and recurrence of candidiasis. There are several potential mechanisms by which hyperglycemia may facilitate vaginal candida colonization. Hyperglycemia impairs various aspects of host defense, including neutrophils and complement proteins, and also promotes the virulence of infecting organisms in patients with diabetes. To evaluate the effective of propranolol solution application in treatment of diabetic vulvovaginitis.Method: Diabetic patients were diagnosed diabetic vulvovaginitis were divided into test group and control group with the method of randomized controlled trial. The patients of test group were treated with local application of propranolol solution once a day. The patients of control group were treated vaginal douch applied locally on vaginal and local on vulva once a day. The course of treatment was 10-d.Result: The curative indexes included the improvement of symptoms and signs of Vulvovaginitis first pain relief, burning sensation, hotness, swelling and vaginal discharge, in group. A symptoms cures in 80%,in group B symptoms cure in 12% side effect of treatment in group A no side effect in group A nor in group B vaginal.Conclusion: Propranolol application promising for the treatment of diabetic Vulvovaginitis in symptomatic women it combat symptoms.

Local Application of Propranolol and Treatment of Diabetic Vulovagnitis

Background: Propranolol (PRO) is a commonly used non-selective beta-adrenergic receptor antagonist used in the treatment of hypertension, angina, anxiety, cardiac arrhythmia, hyperthyroidism, essential tremor and as a prophylaxis against migraine, variceal bleeding and myocardial infarction diabetes mellitus (T2DM) is a debilitating disease with multiple complications resulting from hyperglycemia, inflammation, and possibly immune dysfunction. It is well established that yeasts thrive in a sugar-rich environment, and therefore, it is logical to hypothesize that high glucose concentrations in patients with diabetes may be responsible for promoting the occurrence and recurrence of candidiasis. There are several potential mechanisms by which hyperglycemia may facilitate vaginal candida colonization. Hyperglycemia impairs various aspects of host defense, including neutrophils and complement proteins, and also promotes the virulence of infecting organisms in patients with diabetes. To evaluate the effective of propranolol solution application in treatment of diabetic vulvovaginitis.Method: Diabetic patients were diagnosed diabetic vulvovaginitis were divided into test group and control group with the method of randomized controlled trial. The patients of test group were treated with local application of propranolol solution once a day. The patients of control group were treated vaginal douch applied locally on vaginal and local on vulva once a day. The course of treatment was 10-d.Result: The curative indexes included the improvement of symptoms and signs of Vulvovaginitis first pain relief, burning sensation, hotness, swelling and vaginal discharge, in group. A symptoms cures in 80%,in group B symptoms cure in 12% side effect of treatment in group A no side effect in group A nor in group B vaginal.Conclusion: Propranolol application promising for the treatment of diabetic Vulvovaginitis in symptomatic women it combat symptoms.

The Sedative Effect of Propranolol on Critically Ill Patients: A Case Series.

Recent studies have examined the effectiveness of alpha-2 adrenergic agonists for controlling delirium and agitation. Propranolol, a non-selective beta-adrenergic antagonist with good penetration of the blood-brain barrier, has not been investigated for this purpose. We retrospectively reviewed the medical records of all patients who were prescribed propranolol in our Medical Surgical ICU from January 1, 2010, to December 31, 2013. We recorded the sedation level and daily dose of sedatives, analgesics, and antipsychotics administered each day for 6 days after starting propranolol, and compared them to the day before starting propranolol. Sixty-four patients met inclusion criteria. Thirty-eight episodes met exclusion criteria, leaving 27 patients (31 episodes). The administration of propranolol was associated with significant reductions in fentanyl equivalents (65%, p = 0.009), midazolam equivalents (57%, p = 0.048), propofol (16%, p = 0.009), and haloperidol (44%, p = 0.024) on day 2 after starting propranolol compared with baseline. A stratified analysis showed that these decreases were seen regardless of clinical improvement or deterioration. The use of propranolol was associated with a significant reduction in doses of sedatives and analgesia. Further studies are needed to determine whether propranolol may be a useful adjuvant for managing delirium and agitation in the ICU.

Repurposing Drugs in Oncology (ReDO)-Propranolol as an anti-cancer agent.

Propranolol (PRO) is a well-known and widely used non-selective beta-adrenergic receptor antagonist (beta-blocker), with a range of actions which are of interest in an oncological context. PRO displays effects on cellular proliferation and invasion, on the immune system, on the angiogenic cascade, and on tumour cell sensitivity to existing treatments. Both pre-clinical and clinical evidence of these effects, in multiple cancer types, is assessed and summarised and relevant mechanisms of action outlined. In particular there is evidence that PRO is effective at multiple points in the metastatic cascade, particularly in the context of the post-surgical wound response. Based on this evidence the case is made for further clinical investigation of the anticancer effects of PRO, particularly in combination with other agents. A number of trials are on-going, in different treatment settings for various cancers.

Beta-adrenergic receptor blockers effects on the antinociceptive action of imipramine against thermal induced pain in albino mice

Abstract Introduction: Tricyclic antidepressant have been shown to be effective in treatment of pain of varying etiology, monoaminergic system seems to be implicated in this phenomena. This research examines the role of beta-adrenergic receptor blockers on the antinociceptive effect of imipramine in albino mice using thermal model of pain. Methods: Different groups of five animals each were injected intraperitoneal by different doses of imipramine only (2.5, 7.5,15, 30 mg/kg), atenolol (2 mg/kg), propranolol (6mg/kg), or the combination of the different doses of imipramine with the fixed dose of atenolol or propranolol. The degree of analgesia was measured as an increase in reaction time to pain in the hot plate one hour after drugs injections. Results: Imipramine produced dose dependent increase in reaction time from 129% with the lowest dose to 196% with the highest dose. One-way ANOVA analysis has shown that the addition of a fixed dose of propranolol antagonized significantly the increase in reaction time to 75% with the lowest dose and 118.9% with the highest dose of imipramine. On the other hand, atenolol failed to antagonize significantly the increase in reaction time induced by imipramine. Conclusion: Imipramine has a significant analgesic effect on albino mice in the hot plate test. The antinociceptive action of imipramine seems to be of central origin and possibly mediated, at least in part, by beta adrenergic receptors, as this analgesic effect can be blocked by propranolol, a centrally acting non-selective beta adrenergic receptor antagonist, but not with atenolol which blocks only the peripheral beta receptors.

Three Cases of Infantile Hemanioma Treated with Topical Timolol

Infantile hemangioma is a common, benign tumor of infancy. Although systemic propranolol was found to be effective in the treatment of infantile hemangioma, its use is often challenging for clinicians owing to its potential side effects. Recent small studies have suggested that the topical use of timolol maleate gel, a non-selective beta-adrenergic antagonist, might be effective for the treatment of superficial infantile hemangioma. Here, we report three cases of infantile hemangioma of different sizes and depths treated with the topical timolol maleate gel-forming solution.

Does Long-Term Administration of a Beta-Blocker (Timolol) Induce Fibril-Based Cataract Formation In-vivo?

Timolol is a non-selective beta-adrenergic receptor antagonist administered for treating glaucoma, heart attacks and hypertension. In the present study, we set out to determine whether or not timolol can provoke cataract formation, thus the influence of timolol on the amyloid-type aggregation of crystallin was investigated. We then provided experimental evidence of crystallin aggregation and its induction by timolol using different spectroscopic measurements. Turbidimetric measurements as well as ThT fluorescence data indicated that timolol induce extent of crystallin amyloid formation. The kinetic of protein aggregation was also changed in presence of increasing concentrations of the drug suggesting that long-term drug administration may contribute to the development of cataract. Since the consequence of timolol-crystallin interaction has yet to be identified, additional data on it may help us to postpone amyloid cataract formation.

How should propranolol be initiated for infantile hemangiomas: Inpatient versus outpatient?

How should propranolol be initiated for infantile hemangiomas: Inpatient versus outpatient?

Clinical efficacy and therapeutic mechanisms of propranolol for infancy hemangiomas: an update

Infancy hemangiomas (IHs) are the most common benign tumor of infancy.Earlytherapy has been recommended for proliferating IHs to prevent serious complications.As a non selective beta-adrenergic receptor antagonist,propranolol is commonly used in clinical practice.Recently,more and more studies have reported that propranolol has a good efficacy in the treatment of IHs.The possible therapeutic mechanisms of propranolol in IH include suppression of vascular endothelial growth factor (VEGF) production,inhibition of the hypoxia-inducible factor I (HIF-1) a-VEGF-A axis,downregulation of matrix metalloproteinases (MMPs) and endothelial nitric oxide synthase,and so on. Key words: Hemangiomas ; Infancy ; Propranolol

NDP-MSH inhibits neutrophil migration through nicotinic and adrenergic receptors in experimental peritonitis

Melanocortin is a potent anti-inflammatory molecule. However, little is known about the effect of melanocortin on acute inflammatory processes such as neutrophil migration. In the present study, we investigated the ability of [Nle4, D-Phe7]-melanocyte-stimulating hormone (NDP-MSH), a semisynthetic melanocortin compound, in the inhibition of neutrophil migration in carrageenin-induced peritonitis model. Herein, subcutaneous pretreatment with NDP-MSH decreased neutrophil trafficking in the peritoneal cavity in a dose-dependent manner. NDP-MSH inhibited vascular leakage, leukocyte rolling, and adhesion and reduced peritoneal macrophage inflammatory protein 2, but not TNF-alpha, IL-1beta, IL-10, and keratinocyte-derived chemokine production. In addition, the effect on neutrophil migration was reverted by the pretreatment with both propranolol (a nonselective beta-adrenergic antagonist) and mecamylamine (a nonselective nicotinic antagonist) but not by splenectomy surgery. Moreover, NDP-MSH intracerebroventricular administration inhibited neutrophil migration, indicating participation of the central nervous system. Our results propose that the NDP-MSH effect may be due to a spleen-independent neuro-immune pathway that efficiently regulates excessive neutrophil recruitment to tissues.