BACKGROUND: Obesity is associated with resistance to the metabolic (glucose uptake) and vascular (nitric-oxide mediated dilation and microvascular recruitment) actions of insulin. These vascular effects contribute to insulin sensitivity by increasing tissue delivery of glucose. Studies by us and others suggest that sympathetic activation contributes to insulin resistance to glucose uptake. Here we tested the hypothesis that sympathetic activation contributes to impaired insulin-mediated vasodilation in adult subjects with obesity.
RESULTS: In a randomized crossover study, we used a euglycemic hyperinsulinemic clamp in 12 subjects with obesity to induce forearm arterial vasodilation (forearm blood flow) and microvascular recruitment (contrast-enhanced ultrasonography) during an intrabrachial infusion of saline (control) or phentolamine (sympathetic blockade). Insulin increased forearm blood flow on both study days (from 2.21±1.22 to 4.89±4.21 mL/100 mL per min, P=0.003 and from 2.42±0.89 to 7.19±3.35 mL/100 mL per min, P=0.002 for the intact and blocked day, respectively). Sympathetic blockade with phentolamine resulted in a significantly greater increase in microvascular flow velocity (∆microvascular flow velocity: 0.23±0.65 versus 2.51±3.01 arbitrary intensity units (AIU/s) for saline and phentolamine respectively, P=0.005), microvascular blood volume (∆microvascular blood volume: 1.69±2.45 versus 3.76±2.93 AIU, respectively, P=0.05), and microvascular blood flow (∆microvascular blood flow: 0.28±0.653 versus 2.51±3.01 AIU2/s, respectively, P=0.0161). To evaluate if this effect was not due to nonspecific vasodilation, we replicated the study in 6 subjects with obesity comparing intrabrachial infusion of phentolamine to sodium nitroprusside. At doses that produced similar increases in forearm blood flow, insulin-induced changes in microvascular flow velocity were greater during phentolamine than sodium nitroprusside (%microvascular flow velocity=58% versus 29%, respectively, P=0.031).
CONCLUSIONS: We conclude that sympathetic activation impairs insulin-mediated microvascular recruitment in adult subjects with obesity.

Type 1 diabetes recipients of intrahepatic islet transplantation exhibit glucose-dependent suppression of insulin and activation of glucagon secretion in response to insulin-induced hypoglycemia associated with clinical protection from hypoglycemia. Whether sympathetic activation of adrenergic receptors on transplanted islets is required for these responses in defense against hypoglycemia is not known. To evaluate the adrenergic contribution to posttransplant glucose counterregulation, we performed a randomized, double-blind crossover study of responses during a hyperinsulinemic euglycemic-hypoglycemic clamp under phentolamine (α-adrenergic blockage), propranolol (β-adrenergic blockage), or placebo infusion. Characteristics of participants (5 females/4 males) were as follows: median (range) age 53 (34-63) yr, diabetes duration 29 (18-56) yr, posttransplant 7.0 (1.9-8.4) yr, HbA1c 5.8 (4.5-6.8)%, insulin in-/dependent 5/4, all on tacrolimus-based immunosuppression. During the clamp, blood pressure was lower with phentolamine and heart rate was lower with propranolol versus placebo (P < 0.05). There was no difference in the suppression of endogenous insulin secretion (derived from C-peptide measurements) during the euglycemic or hypoglycemic phases, and although levels of glucagon were similar with phentolamine or propranolol vs. placebo, the increase in glucagon from eu- to hypoglycemia was greater with propranolol vs. placebo (P < 0.05). Pancreatic polypeptide was greater with phentolamine versus placebo during the euglycemic phase (P < 0.05), and free fatty acids were lower and the glucose infusion rate was higher with propranolol versus placebo during the hypoglycemic phase (P < 0.05 for both). These results indicate that neither physiological α- nor β-adrenergic blockade attenuates transplanted islet responses to hypoglycemia, suggesting sympathetic reinnervation of the islet graft is not necessary for posttransplant glucose counterregulation.NEW & NOTEWORTHY Whether adrenergic input to islets is necessary for glucose homeostasis in humans is debated. Here, the adrenergic contribution to intrahepatically transplanted islet cell responses to hypoglycemia in individuals with type 1 diabetes was investigated through α- or β-adrenergic receptor blockade during hyperinsulinemic euglycemic-hypoglycemic clamps. Neither α- nor β-adrenergic blockage affected the suppression of endogenous insulin or activation of glucagon secretion, suggesting that sympathetic reinnervation of islet grafts is not required for posttransplant defense against hypoglycemia.

BACKGROUND: For successfully managing pediatric dental patients, local anesthesia is essential to eliminate pain during or after the operative period. An early recovery from soft-tissue anesthesia after an inferior alveolar nerve block (IANB) should benefit a young child patient by avoiding the risk of inadvertently biting the soft tissues.
OBJECTIVE: Hence, the purpose of the study was to (1) evaluate and compare the efficacy of pre- and postoperative ibuprofen on pain perception in children who undergo IANB anesthesia with or without the use of PM and (2) evaluate the average time required for reversal of anesthesia symptoms using phentolamine mesylate.
METHODS: The present study was a randomized, clinical trial performed among 60 children between 6 and 8 years of age using a convenient sampling method. The children were randomly assigned into four equal groups of 15 each using the computer-generated randomization sequence. IANB anesthesia was performed using 2% lignocaine with 1:100,000 epinephrine, and a mandibular primary molar pulpotomy was performed on each group. Group 1: the ibuprofen tablet was taken 1 h before the onset of the procedure. Group 2: ibuprofen tablet 30 min after the pulpotomy procedure. Group 3: the ibuprofen tablet was taken 1 h before the onset of the procedure, and the Phentolamine mesylate (PM) injection was administered. Group 4: immediately after the pulpotomy, the PM injection was administered, and an ibuprofen tablet was taken 30 min after the pulpotomy procedure. All children were assessed for the duration of soft-tissue anesthesia, their behavior scores and pain rating, as well as the incidence of postoperative self-inflicted injuries.
METHODS: A one-way ANOVA was used to compare the average time needed for the reversal of anesthetic symptoms between groups. The effects of phentolamine, local anesthetics, and ibuprofen on the child\'s behavior and pain scores were compared using the Student\'s t-test. For the study, P < 0.05 was accepted as statistically significant.
RESULTS: The time needed for the full reversal of anesthetic symptoms to manifest on the tongue and lip was substantially reduced by the injection of phentolamine (P < 0.001). The use of phentolamine for reversal or the intake of ibuprofen pre- or postoperatively did not exhibit any significant variation in the behavior, pain experience, or incidence of self-inflicted injuries in the child.
CONCLUSIONS: It is evident that although phentolamine injections shorten the duration of anesthesia, the adjunctive use of pre- or postoperative ibuprofen did not significantly alter pain scores.

暂无摘要。

UNASSIGNED: Extravasation is the erroneous delivery of IV medication or fluid into the extravascular space. Complications ranging from mild injury to amputation can result, depending on the physical and pharmacologic properties of the infusate. Children are at increased risk for extravasation injuries. There is a paucity of data on the treatment and outcomes of extravasation injuries, particularly in terms of the role of pharmacologic antidotes.
UNASSIGNED: To describe the incidence of extravasation at a tertiary pediatric care centre (as an update to a previous study), to identify the agents most commonly involved in extravasation injuries, to describe the antidotes used for management of injuries and their related adverse drug effects, and to describe complications related to injuries.
UNASSIGNED: The medical records of pediatric patients who experienced an extravasation injury at the BC Children\'s and BC Women\'s Hospitals, between September 1, 2008, and September 30, 2020, were reviewed. Data regarding management (adherence with institutional protocol) and outcomes of injuries were collected.
UNASSIGNED: The 242 charts included in the analysis noted a total of 245 extravasation injuries, for an extravasation incidence of 0.04% per patient-day. Of the 242 patients, 110 were excluded from secondary outcome analysis due to lack of data detailing the extravasation event. Of the remaining 132 patients, the majority were neonates (n = 54, 40.9%), infants (n = 33, 25.0%), and children (n = 34, 25.8%), and more than a third were treated on general pediatric wards (n = 50, 37.9%). The medications most frequently involved were total parenteral nutrition with lipids (36/132, 27.3%), vancomycin (36/132, 27.3%), and IV fluids (35/132, 26.5%). Most of the patients had mild outcomes and recovered without complications. No adverse drug events from antidotes were reported.
UNASSIGNED: The incidence of extravasation at the study institution remained low, with the medications involved being similar to those reported in the literature and the majority of patients having mild outcomes. Additional prospective studies are needed to assess the efficacy and safety of antidotes administered for extravasation injuries.
UNASSIGNED: L’extravasation est l’administration erronée de médicaments ou de liquides IV dans l’espace extravasculaire. Des complications allant d’une blessure légère à l’amputation peuvent en résulter, en fonction des propriétés physiques et pharmacologiques de la perfusion. Les enfants courent un risque accru de blessures par extravasation. Il existe peu de données sur le traitement et les conséquences des blessures par extravasation, notamment en ce qui concerne le rôle des antidotes pharmacologiques.
UNASSIGNED: Décrire l’incidence des extravasations dans un centre de soins pédiatriques tertiaires (en tant que mise à jour d’une étude précédente), recenser les agents les plus couramment impliqués dans les blessures par extravasation, décrire les antidotes utilisés pour la gestion des blessures et leurs effets indésirables liés aux médicaments et décrire les complications liées aux blessures.
UNASSIGNED: Les dossiers médicaux des patients pédiatriques ayant subi une blessure par extravasation entre le 1er septembre 2008 et le 30 septembre 2020 aux hôpitaux BC Children’s Hospital et BC Women’s Hospital ont été examinés. Des données concernant la prise en charge (c’est-à-dire le respect du protocole de l’établissement) et les conséquences des blessures ont été recueillies.
UNASSIGNED: Les 242 dossiers inclus dans l’analyse indiquaient un total de 245 blessures par extravasation, pour une incidence d’extravasation de 0,04 % par jour-patient. Parmi les 242 patients, 110 ont été exclus de l’analyse secondaire des conséquences en raison d’un manque de données concernant les détails de l’extravasation. Sur les 132 patients restants, la majorité était des nouveau-nés (n = 54, 40,9 %), des nourrissons (n = 33, 25,0 %) et des enfants (n = 34, 25,8 %) et plus du tiers ont reçu des soins dans un service de pédiatrie générale (n = 50, 37,9 %). Les médicaments les plus fréquemment impliqués étaient la nutrition parentérale totale avec des lipides (36/132, 27,3 %), la vancomycine (36/132, 27,3 %) et des liquides IV (35/132, 26,5 %). Les conséquences sur la plupart des patients étaient bénignes et ils se sont rétablis sans complications. Aucun effet indésirable lié aux antidotes n’a été signalé.
UNASSIGNED: L’incidence des extravasations dans l’établissement à l’étude est restée faible, les médicaments impliqués étant similaires à ceux rapportés dans la littérature et les conséquences pour la majorité des patients étaient bénignes. Des études prospectives supplémentaires sont nécessaires pour évaluer l’efficacité et la sécurité des antidotes administrés pour les blessures par extravasation.

This article discusses the prevalence and impact of pharmacologically-induced mydriasis, a condition where the pupil becomes excessively dilated due to certain drugs. It highlights the challenges faced by medical professionals in dealing with this condition and the limitations of current treatments, like pilocarpine and dapiprazole, which come with systemic side effects and specific contraindications, limiting their regular use. The article introduces Ryzumvi, a novel ophthalmic solution approved by the US FDA, which effectively reverses mydriasis caused by adrenergic agonists and antimuscarinic drugs. The article provides insights into its mechanism of action, clinical efficacy, pharmacokinetics, safety, and tolerance based on extensive clinical trials. It emphasizes its rapid onset of action and effectiveness in restoring pupils to their initial size. It also underlines the potential for expanded applications, including in pediatric patients, solidifying its importance in the field of ophthalmology. Furthermore, Ryzumvi represents a promising advancement in managing pharmacologically-induced mydriasis, offering swift and effective relief while highlighting the importance of adhering to safety precautions and the continuous research and development efforts in ophthalmology to comprehensively address vision-related disorders and enhance patient outcomes.

Heart failure with preserved ejection fraction (HFpEF) has been characterized by lower blood flow to exercising limbs and lower peak oxygen utilization ( V ̇ O 2 ${{\\dot{V}}_{{{{\\mathrm{O}}}_{\\mathrm{2}}}}}$ ), possibly associated with disease-related changes in sympathetic (α-adrenergic) signaling. Thus, in seven patients with HFpEF (70 ± 6 years, 3 female/4 male) and seven controls (CON) (66 ± 3 years, 3 female/4 male), we examined changes (%Δ) in leg blood flow (LBF, Doppler ultrasound) and leg V ̇ O 2 ${{\\dot{V}}_{{{{\\mathrm{O}}}_{\\mathrm{2}}}}}$ to intra-arterial infusion of phentolamine (PHEN, α-adrenergic antagonist) or phenylephrine (PE, α1-adrenergic agonist) at rest and during single-leg knee-extension exercise (0, 5 and 10 W). At rest, the PHEN-induced increase in LBF was not different between groups, but PE-induced reductions in LBF were lower in HFpEF (-16% ± 4% vs. -26% ± 5%, HFpEF vs. CON; P < 0.05). During exercise, the PHEN-induced increase in LBF was greater in HFpEF at 10 W (16% ± 8% vs. 8% ± 5%; P < 0.05). PHEN increased leg V ̇ O 2 ${{\\dot{V}}_{{{{\\mathrm{O}}}_{\\mathrm{2}}}}}$ in HFpEF (10% ± 3%, 11% ± 6%, 15% ± 7% at 0, 5 and 10 W; P < 0.05) but not in controls (-1% ± 9%, -4% ± 2%, -1% ± 5%; P = 0.24). The \'magnitude of sympatholysis\' (PE-induced %Δ LBF at rest - PE-induced %Δ LBF during exercise) was lower in patients with HFpEF (-6% ± 4%, -6% ± 6%, -7% ± 5% vs. -13% ± 6%, -17% ± 5%, -20% ± 5% at 0, 5 and 10 W; P < 0.05) and was positively related to LBF, leg oxygen delivery, leg V ̇ O 2 ${{\\dot{V}}_{{{{\\mathrm{O}}}_{\\mathrm{2}}}}}$ , and the PHEN-induced increase in LBF (P < 0.05). Together, these data indicate that excessive α-adrenergic vasoconstriction restrains blood flow and limits V ̇ O 2 ${{\\dot{V}}_{{{{\\mathrm{O}}}_{\\mathrm{2}}}}}$ of the exercising leg in patients with HFpEF, and is related to impaired functional sympatholysis in this patient group. KEY POINTS: Sympathetic (α-adrenergic)-mediated vasoconstriction is exaggerated during exercise in patients with heart failure with preserved ejection fraction (HFpEF), which may contribute to limitations of blood flow, oxygen delivery and oxygen utilization in the exercising muscle. The ability to adequately attenuate α1-adrenergic vasoconstriction (i.e. functional sympatholysis) within the vasculature of the exercising muscle is impaired in patients with HFpEF. These observations extend our current understanding of HFpEF pathophysiology by implicating excessive α-adrenergic restraint and impaired functional sympatholysis as important contributors to disease-related impairments in exercising muscle blood flow and oxygen utilization in these patients.

OBJECTIVE: Feeding intolerance (FI) is a common problem in late preterm infants (34 weeks ≤ gestational age < 37 weeks). This study aimed to evaluate the efficacy and safety of phentolamine combined with B vitamins in treating FI in late preterm infants and to explore its effects on gastrointestinal symptoms, inflammation and complications.
METHODS: We randomly assigned 118 late preterm infants with FI to a treatment group (n = 56) or a control group (n = 62). The treatment group received intravenous phentolamine and intramuscular B vitamins, whereas the control group received basic treatment only. We measured the time of disappearance of gastrointestinal symptoms, the time of basal at-tainment, the time of hospitalisation, the incidence of complications, the concentrations of inflammatory markers and the overall effective rate of treatment.
RESULTS: The treatment group had a shorter duration of gastrointestinal symptoms than did the control group (p < 0.01). The treatment group also had lower concentrations of inflammatory markers and a higher overall effective rate than did the control group (p < 0.05). There was no difference between the two groups in the time of hospitalisation, basal attainment, weight re-covery and the incidence of complications (p > 0.05).
CONCLUSIONS: Phentolamine and B vitamins can reduce gastrointestinal symptoms and inflammation in late preterm infants with FI but do not affect the occurrence of complications.

BACKGROUND: Although oral phosphodiesterase 5 inhibitors represent a first choice and long-term option for about half of all patients with erectile dysfunction (ED), self-injection therapy with vasoactive drugs remains a viable alternative for all those who are not reacting or cannot tolerate oral drug therapy. This current injection therapy has an interesting history beginning in 1982.
OBJECTIVE: To provide a comprehensive history of self-injection therapy from the very beginnings in 1982 by contemporary witnesses and some members of the International Society for Sexual Medicine\'s History Committee, a complete history of injection therapy is prepared from eyewitness accounts and review of the published literature on the subject, as well as an update of the current status of self-injection therapy.
METHODS: Published data on injection therapy, as a diagnostic and therapeutic tool for ED, were reviewed thoroughly by PubMed and Medline research from 1982 until June 2023. Early pioneers and witnesses added firsthand details to this historical review. Therapeutic reports of injection therapy were reviewed, and results of side effects and complications were thoroughly reviewed.
RESULTS: The pioneers of the first hours were Ronal Virag (1982) for papaverine, Giles Brindley (1983) for cavernosal alpha-blockade (phentolamine and phenoxybenzamine), Adrian Zorgniotti (1985) for papaverine/phentolamine, and Ganesan Adaikan and N. Ishii (1986) for prostaglandin E1. Moxisylyte (thymoxamine) was originally marketed but later withdrawn. The most common side effect is priapism, with the greatest risk of this from papaverine, which has modified its use for therapy. Currently, prostaglandin E1 and trimixes continue to be the agents of choice for diagnostic and therapeutic use in ED. A recent agent is a mixture of a vasoactive intestinal polypeptide (aviptadil) and phentolamine.
CONCLUSIONS: After 40 years, self-injection therapy represents the medication with the highest efficacy and reliability rates and remains a viable option for many couples with ED. The history of this therapy is rich.

BACKGROUND: Phentolamine is an α-adrenergic receptor blocker that can be used to treat neonatal pneumonia, but its underlying mechanism is unclear. The purpose of this study is to probe the function of phentolamine on lipopolysaccharide (LPS)-induced inflammation and cell death in an in vitro model of neonatal pneumonia.
METHODS: Human MRC-5 cells were incubated with varying doses of phentolamine in vitro to evaluate cell viability. Subsequently, LPS was introduced to further investigate the combined effects of phentolamine and LPS on cell viability and apoptosis in MRC-5 cells. The effect of phentolamine/LPS treatment on the Neurotrophic Tyrosine Kinase Receptor A (TrkA)/Protein Kinase B (Akt) signaling pathway and the phosphorylation of pathway proteins in MRC-5 cells was further analyzed via western blot. Additionally, knockout of TrkA and Akt genes in MRC-5 cells was performed to explore the effects of phentolamine/LPS treatment on cell viability, apoptosis levels, and inflammatory factor levels in MRC-5 cells.
RESULTS: Preincubation of MRC-5 cells with a low concentration of phentolamine (≤6 μg/mL) protected against LPS-induced cell inflammatory injury. Phentolamine promoted both TrkA and Akt phosphorylation and Akt activation induced by LPS in MRC-5 cells. The protective effect of phentolamine against LPS-induced apoptosis and inflammation was significantly reduced in response to TrkA or Akt gene knockdown in MRC-5 cells.
CONCLUSIONS: Phentolamine may protect LPS-induced apoptosis and inflammation by activating the TrkA and Akt signaling pathways.