-
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 -
The Journal of Clinical Investigation Apr 2024Infantile hemangioma (IH) is a benign vascular tumor that occurs in 5% of newborns. The tumor follows a life cycle of rapid proliferation in infancy, followed by slow... (Review)
Review
Infantile hemangioma (IH) is a benign vascular tumor that occurs in 5% of newborns. The tumor follows a life cycle of rapid proliferation in infancy, followed by slow involution in childhood. This unique life cycle has attracted the interest of basic and clinical scientists alike as a paradigm for vasculogenesis, angiogenesis, and vascular regression. Unanswered questions persist about the genetic and molecular drivers of the proliferating and involuting phases. The beta blocker propranolol usually accelerates regression of problematic IHs, yet its mechanism of action on vascular proliferation and differentiation is unclear. Some IHs fail to respond to beta blockers and regrow after discontinuation. Side effects occur and long-term sequelae of propranolol treatment are unknown. This poses clinical challenges and raises novel questions about the mechanisms of vascular overgrowth in IH.
Topics: Infant, Newborn; Humans; Vascular Neoplasms; Propranolol; Disease Progression; Physicians; Hemangioma
PubMed: 38618963
DOI: 10.1172/JCI172836 -
Iranian Journal of Child Neurology 2024Migraine is a chronic and joint disease in children. The results of previous studies on the effectiveness of probiotics in preventing migraine attacks in children have...
OBJECTIVES
Migraine is a chronic and joint disease in children. The results of previous studies on the effectiveness of probiotics in preventing migraine attacks in children have been controversial. This study aims to investigate the effect of probiotics on migraine prophylaxis in children.
MATERIALS & METHODS
In this clinical trial study, 41 children aged 5 to 15 with migraine enrolled the study in two control and intervention groups. Children in the intervention group (18 children) received propranolol at a dose of 1 mg per kilogram of body weight daily in two divided doses along with a 250 mg Yomogi capsule daily for three months, and children in the control group (23 children), received propranolol along with placebo for three months. The study compared the frequency and duration of headache days, PedMIDAS criteria, and parental satisfaction between the two groups before treatment, as well as one month and three months post-treatment.
RESULTS
The number of headache days in both groups decreased over time, but in the intervention group, this decrease was more than the control group was statistically significant (P=0.045). The average PedMIDAS scale after treatment in the intervention group was 3.9 ± 3.8; in the control group, it was 8.4 ± 8.2, which was statistically significant (P=0.047). Parents' satisfaction with the treatment was statistically significantly higher in the intervention group (94.4%) than in the control group (54.5%) (P=0.011). No significant drug complications were seen in any of the two groups.
CONCLUSION
In children with migraine, adding probiotics to migraine treatment reduces the intensity and number of days of children's headaches and increases the Parents' satisfaction with the treatment.
PubMed: 38617394
DOI: 10.22037/ijcn.v17i4.39598 -
International Journal of Molecular... Mar 2024Adrenergic pathways represent the main channel of communication between the nervous system and the immune system. During inflammation, blood monocytes migrate within...
Adrenergic pathways represent the main channel of communication between the nervous system and the immune system. During inflammation, blood monocytes migrate within tissue and differentiate into macrophages, which polarize to M1 or M2 macrophages with tissue-damaging or -reparative properties, respectively. This study investigates whether the β-adrenergic receptor (β-AR)-blocking drug propranolol modulates the monocyte-to-macrophage differentiation process and further influences macrophages in their polarization toward M1- and M2-like phenotypes. Six-day-human monocytes were cultured with M-CSF in the presence or absence of propranolol and then activated toward an M1 pro-inflammatory state or an M2 anti-inflammatory state. The chronic exposure of monocytes to propranolol during their differentiation into macrophages promoted the increase in the M1 marker CD16 and in the M2 markers CD206 and CD163 and peroxisome proliferator-activated receptor ɣ expression. It also increased endocytosis and the release of IL-10, whereas it reduced physiological reactive oxygen species. Exposure to the pro-inflammatory conditions of propranolol-differentiated macrophages resulted in an anti-inflammatory promoting effect. At the molecular level, propranolol upregulated the expression of the oxidative stress regulators NRF2, heme oxygenase-1 and NQO1. By contributing to regulating macrophage activities, propranolol may represent a novel anti-inflammatory and immunomodulating compound with relevant therapeutic potential in several inflammatory diseases.
Topics: Humans; Monocytes; Propranolol; Antioxidants; NF-E2-Related Factor 2; Macrophages; Anti-Inflammatory Agents
PubMed: 38612493
DOI: 10.3390/ijms25073683 -
Molecules (Basel, Switzerland) Apr 20244-Nitro and 7-nitro propranolol have been recently synthesized and characterized by us. (±)-4-NO-propranolol has been shown to act as a selective antagonist of...
4-Nitro and 7-nitro propranolol have been recently synthesized and characterized by us. (±)-4-NO-propranolol has been shown to act as a selective antagonist of 6-nitrodopamine (6-ND) receptors in the right atrium of rats. As part of our follow-up to this study, herein, we describe the first synthesis of (±)-3-nitroatenolol as a probe to evaluate the potential nitration of atenolol by endothelium. Chiral chromatography was used to produce pure enantiomers. By using Riguera's method, which is based on the sign distribution of ΔδH, the absolute configuration of the secondary alcohol was determined.
PubMed: 38611877
DOI: 10.3390/molecules29071598 -
Journal of Family Medicine and Primary... Feb 2024Approximately 15% of migraine sufferers need preventative medicine because they have more than two episodes each month. Migraine is a regular, persistent condition that...
BACKGROUND
Approximately 15% of migraine sufferers need preventative medicine because they have more than two episodes each month. Migraine is a regular, persistent condition that frequently makes victims helpless. Numerous drugs from various classes have so far been used in migraine prophylaxis. Their effectiveness is recurrently overshadowed by their side effects because they must be used for a long time, which occasionally necessitates stopping the drug.
MATERIALS AND METHODS
In the tertiary care teaching hospital's department of medicine, a prospective, comparative, open-label study was initiated. Two groups of 80 patients were randomly chosen. For 3 months, the 40 patients in Group A were given a tablet of amitriptyline 10 mg once daily, whereas the 40 patients in Group B were given a tablet of propranolol 20 mg once a day. At the conclusion of the fourth, eighth, and twelfth weeks, the patients' own self-assessment migraine diary and a 4-point pain scale were used to grade the intensity of the headaches.
RESULTS
As a result, in Group A, the mean migraine attack severity in periods 1 and 2 was 5.88 2.69 and 5.41 2.48, respectively. In Group B, the mean was 5.15 2.75 in period 1 and 5.66 2.78 in period 2, respectively. The average length of a migraine attack in Group A was 20.30 5.61 h in period 1 and 16.75 5.23 h in period 2. In Group B, the mean was 16.59 3.21 in period 1 and 18.78 5.14 in period 2. Between groups A and B, there was a statistically significant difference.
CONCLUSION
The average number of migraine attacks reduced in the amitriptyline and propranolol groups as the treatment duration increased. Amitriptyline is a popular medication with established effectiveness and manageable levels of negative side effects. It is the tricyclic antidepressant that is most frequently used to prevent headaches. When administered for migraine prevention, it generates a quick response within 3 months. Propranolol is less effective than amitriptyline at reducing the frequency, length, and severity of episodes.
PubMed: 38605779
DOI: 10.4103/jfmpc.jfmpc_927_23 -
Asian Journal of Surgery Jul 2024
Topics: Humans; Propranolol; Infant; Hemangioma; Female; Male; Treatment Outcome; Adrenergic beta-Antagonists; Eyelid Neoplasms; Retrospective Studies
PubMed: 38599964
DOI: 10.1016/j.asjsur.2024.03.169