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- Attenuated aortic vasodilation and sympathetic prejunctional facilitation in epinephrine-deficient mice: selective impairment of β2-adrenoceptor responses. [JOURNAL ARTICLE]
- J Pharmacol Exp Ther 2014 Aug 26.
It has been suggested that there is a link between epinephrine synthesis and the development of β2-adrenoceptor-mediated effects, but it remains to be determined if this development is triggered by epinephrine. The aim of this study was to characterize the β-adrenoceptor-mediated relaxation and facilitation of norepinephrine release in the aorta of phenylethanolamine-N-methyltransferase-knockout (Pnmt-KO) mice. Catecholamines were quantified by reverse-phase HPLC-ED. Aorta rings were mounted in a myograph to determine concentration-response curves to selective β1- or β2-adrenoceptor agonists in the absence or presence of selective β1- or β2-adrenoceptor antagonists. Aortic rings were also preincubated with (3)H-norepinephrine to measure tritium overflow elicited by electrical stimulation in the presence of increasing concentrations of non-selective β or selective β2-adrenoceptor agonists. β2-adrenoceptor protein density was evaluated by western-blotting and β2-adrenoceptor localization by immunohistochemistry. Epinephrine is absent in Pnmt-KO mice. The potency and the maximal effect of β2-adrenoceptor agonist terbutaline were lower in Pnmt-KO than in WT mice. The selective β2-adrenoceptor antagonist ICI-118551 antagonized the relaxation caused by terbutaline in wild type (WT) but not in Pnmt-KO mice. Isoproterenol and terbutaline induced concentration-dependent increase in tritium overflow in WT mice only. β2-Adrenoceptor protein density was decreased in membrane aorta homogenates of Pnmt-KO mice and this finding was supported by immunofluorescence confocal microscopy. In conclusion, epinephrine is crucial for β2-adrenoceptor-mediated vasodilation and facilitation of norepinephrine release. In the absence of epinephrine, β2-adrenoceptor protein density was decreased in aorta cell membranes, thus potentially hindering its functional activity.
- Dexmedetomidine utilisation and outcomes of children with trisomy 21 undergoing congenital heart disease surgery. [JOURNAL ARTICLE]
- Cardiol Young 2014 Aug 27.:1-5.
Introduction: The diagnosis of trisomy 21 in children has been associated with failed extubation after CHD surgery. Dexmedetomidine may be a useful agent to improve postoperative outcomes in these patients, such as ventilator time, ICU length of stay, or hospital length of stay. Materials and methods: The Pediatric Health Information System database was queried from January, 2008 to December, 2010 for patients with trisomy 21 who underwent CHD surgery. Patients who received dexmedetomidine were matched to patients who did not by propensity score. The primary outcome was ventilator days charged, and secondary outcomes included ICU and hospital length of stay. Results: A total of 1088 patients (544 matched pairs) met inclusion criteria. Patient characteristics were similar, with the exception of more patients in the dexmedetomidine group undergoing repair of complete atrioventricular canal and fewer undergoing mechanical valve replacement (p<0.01). More patients in the dexmedetomidine group were administered milrinone, epinephrine, vasopressin, benzodiazepines, opiates, and adjunct pain and sedative medications (p<0.01). The dexmedetomidine group had greater time on the ventilator [7 (4.5-11) versus 6 (4-10) days (median, interquartile range) p<0.01] and similar ICU length of stay, hospital length of stay, and mortality compared with controls. Mixed-effects modelling clustered on institution did not show beneficial effect of dexmedetomidine on ventilator time, ICU stay, or hospital length of stay. Conclusions: The use of dexmedetomidine was not associated with the decreased ventilatory time. Routine use of dexmedetomidine is not warranted in this patient population.
- Topical hemostatic procedures control blood loss in bilateral cemented single-stage total knee arthroplasty. [JOURNAL ARTICLE]
- J Orthop Sci 2014 Aug 27.
Blood management is critical in total knee arthroplasty (TKA). In bilateral, single stage TKA, blood loss seems more prominent. We believe it is important to control all potential bleeding within the wound tissue.The purpose of the study was to evaluate a series of topical procedures used to reduce blood loss and transfusion in single-stage bilateral cemented total knee arthroplasty: antifibrinolysis with tranexamic acid, vasoconstriction with epinephrine, sealing of the bone section intraoperatively, and closure of the drainage tube within the first 4 h postoperatively.Patients with osteoarthritis of the knees were randomly divided into two groups. In group A, 5 ml (25 mg/ml) tranexamic acid (TXA) and 5 ml analgesic containing epinephrine (3 μg/ml) solution were injected at several points into the posterior capsule before installation of the prosthesis. The femoral medullar canal was closed with autograft bone and then sealed compressively with cement. Before the tourniquet was released, 10 ml TXA solution and 10 ml analgesic containing epinephrine were injected at several points into the periosteum, synovium, joint capsule, tendons, and deep fascia tissue (injection of analgesic containing epinephrine into subcutaneous fat and dermis was avoided). The residual nail holes in the bone and the uncovered bone section were covered with bone wax. The tourniquet was then removed, and active bleeding points were stanched. TXA solution (20 ml) was injected into the articular cavity after wound closure. The drainage tube was clamped for 4 h, then opened. In group B, injection of analgesic containing epinephrine into soft tissue, control of active bleeding, and clamping of the drainage tube for 4-h, only, were performed.Ninety patients were enrolled in the study. Compared with those in group B, intraoperative blood loss, drainage volume, total postoperative blood loss, and number of patients requiring allogenic blood transfusion were significantly reduced in group A. There was no significant difference between the incidence of complications in the groups.Our topical procedures enable effective and safe reduction of blood loss and the number of patients requiring transfusion in single-stage bilateral osteoarthritic TKA.
- Ability of medical students to calculate drug doses in children after their paediatric attachment. [Journal Article]
- Pharm Pract (Granada) 2008 Oct; 6(4):191-6.
Dose calculation errors constitute a significant part of prescribing errors which might have resulted from informal teaching of the topic in medical schools.To determine adequacy of knowledge and skills of drug dose calculations in children acquired by medical students during their clinical attachment in paediatrics.Fifty two 5th year medical students of the Lagos State University College of Medicine (LASUCOM), Ikeja were examined on drug dose calculations from a vial and ampoules of injections, syrup and suspension, and tablet formulation. The examination was with a structured questionnaire mostly in the form of multiple choice questions.Thirty-six (69.2%) and 30 (57.7%) students were taught drug dose calculation in neonatal posting and during ward rounds/ bed-side teaching, respectively. Less than 50% of the students were able to calculate the correct doses of each of adrenaline, gentamicin, chloroquine and sodium bicarbonate injections required by the patient. Dose calculation was however relatively better with adrenalin when compared with the other injections. The proportion of female students that calculated the correct doses of quinine syrup and cefuroxime suspension were significantly higher than those of their male counterparts (p<0.05 and p<0.01, respectively; Chi-square test). When doses calculated in mg/dose and mL/dose was compared for adrenalin injection and each of quinine syrup and cefuroxime suspension, there were significant differences (adrenaline and quinine, p=0.005; adrenaline and cefuroxime, p=0.003: Fischer's exact test). Dose calculation errors of similar magnitude to injections, syrup and suspension were also observed with tablet formulation.LASUCOM medical students lacked the basic knowledge of paediatric drug dose calculations but were willing to learn if the topic was formally taught. Drug dose calculations should be given a prominent consideration in the undergraduate medical curriculum in Nigeria.
- Dietary-induced binge eating increases prefrontal cortex neural activation to restraint stress and increases binge food consumption following chronic guanfacine. [JOURNAL ARTICLE]
- Pharmacol Biochem Behav 2014 Aug 23.
Binge eating is a prominent feature of bulimia nervosa and binge eating disorder. Stress or perceived stress is an often-cited reason for binge eating. One notion is that the neural pathways that overlap with stress reactivity and feeding behavior are altered by recurrent binge eating. Using young adult female rats in a dietary-induced binge eating model (30min access to binge food with or without 24-h calorie restriction, twice a week, for 6weeks) we measured the neural activation by c-Fos immunoreactivity to the binge food (vegetable shortening mixed with 10% sucrose) in bingeing and non-bingeing animals under acute stress (immobilization; 1h) or no stress conditions. There was an increase in the number of immunopositive cells in the dorsal medial prefrontal cortex (mPFC) in stressed animals previously exposed to the binge eating feeding schedules. Because attention deficit hyperactive disorder (ADHD) medications target the mPFC and have some efficacy at reducing binge eating in clinical populations, we examined whether chronic (2weeks; via IP osmotic mini-pumps) treatment with a selective alpha-2A adrenergic agonist (0.5mg/kg/day), guanfacine, would reduce binge-like eating. In the binge group with only scheduled access to binge food (30min; twice a week; 8weeks), guanfacine increased total calories consumed during the 30-min access period from the 2-week pre-treatment baseline and increased binge food consumption compared with saline-treated animals. These experiments suggest that mPFC is differentially activated in response to an immobilization stress in animals under different dietary conditions and chronic guanfacine, at the dose tested, was ineffective at reducing binge-like eating.
- Advanced Clinical Interventions Performed by Emergency Medical Responder Firefighters prior to Ambulance Arrival. [JOURNAL ARTICLE]
- Prehosp Emerg Care 2014 Aug 25.
Abstract Introduction. Data on the clinical interventions performed by emergency medical responder firefighters (EMRFs) are limited outside the context of cardiac arrest. We sought to understand the broader medical role of firefighters by examining fire-ambulance arrival order and documenting specific interventions provided by firefighters with advanced EMR training. Methods. A secondary analysis was conducted using electronic patient care records from a single ambulance service and two municipal fire departments that partner to provide emergency response in two suburbs of Minneapolis, Minnesota. Firefighters in both municipalities are dispatched to all medical calls, regardless of severity, and receive training in the following advanced EMR skills: intravenous line placement, administration of oral nitroglycerin and aspirin, placement of supraglottic airways, administration of albuterol via nebulizer, and injections of intramuscular glucagon and epinephrine. Time stamps for unit arrival on scene were used to determine arrival order and to quantify fire lead time (i.e., the interval EMRFs were on scene before paramedics). Results. Fire and ambulance records were linked for 10,403 patient encounters that occurred over 2.5 years. EMRFs arrived first in 9,001 calls (88%) with an average fire lead time of 4.5 minutes. In the two communities, firefighters performed at least one of the six advanced training interventions in 688 patient encounters (7.6%) when they reached the patient first, the most frequent being intravenous line placement (n = 340; 3.8%) and administration of oral nitroglycerin or aspirin (n = 303; 3.4%). EMRFs arrived first to 96 cases of cardiac arrest and performed chest compressions in 78%, automated external defibrillator use in 44%, supraglottic airway placement in 32%, and intravenous line starts in 18%. A modest positive association was observed between increasing fire lead time and use of cardiac arrest interventions by EMRFs. Conclusions. EMRFs performed advanced EMR training interventions in a small fraction of the patients they were able to reach before paramedics, and further study of the clinical significance of these interventions in the hands of this responder group is needed. EMRF training in these communities should continue to emphasize the fervent and consistent application of BLS resuscitation interventions in victims of cardiac arrest.
- Adipose Cells Induce Phospho-Thr-172 AMPK Production by Epinephrine or CL316243 in Mouse 3T3-L1 Adipocytes or MAPK Activation and G Protein-Associated PI3K Responses Induced by CL316243 or Aluminum Fluoride in Rat White Adipocytes. [Journal Article]
- Folia Biol (Praha) 2014; 60(4):168-79.
Responses of adipose cells to adrenoceptor regulation, including that of β-adrenoceptor (AR), and the signalling machinery involved in these responses are not sufficiently understood; information that is helpful for elucidating the adrenoceptor (adrenergic and β-AR)-responsive machinery is insufficient. We examined phospho-Thr-172 AMPK production in mouse-derived 3T3-L1 adipocytes treated with epinephrine or CL316243 (a β3-AR agonist) for 15 min. We also examined MAPK activation or G protein-associated PI3K activation or -associated PI3K p85 complex formation in rat epididymal (white) adipocytes treated with CL316243 for 15 min or aluminum fluoride (a G-protein signalling activator) for 20 min. Furthermore, we examined the effect of PTX (a trimeric G-protein inactivator) on p85 complex formation induced by aluminum fluoride treatment. Western blot analysis revealed that epinephrine or CL316243 treatment increased the phospho- Thr-172 AMPK (an active form of AMPK) level in 3T3-L1 adipocytes. Activated kinase analysis with a specific substrate showed that CL316243 or aluminum fluoride treatment activated MAPK in rat adipocytes. Immunoprecipitation experiments with a G-protein β subunit (Gβ) antibody showed that treatment of rat adipocytes with CL316243 activated PI3K and increased the PI3K p85 level in the Gβ antibody immunoprecipitates. Such an increase in the p85 level was similarly elicited by aluminum fluoride treatment in a PTX-sensitive manner. Our results provide possible clues for clarifying the signalling machinery involved in adrenoceptor responses, including those of β3-AR, in mouse-derived adipocytes and rat white adipocytes. Our findings advance the understanding of responses to adrenoceptor regulation in adipose cells and of the cellular signalling machinery present in the cells.
- Managing food allergies in schools. [Journal Article]
- Curr Allergy Asthma Rep 2014 Oct; 14(10):467.
Food allergies are estimated to affect as many as 8 % of children with 2.5 % being allergic to peanut products. Based on the results of recent surveys, this prevalence has been increasing over the last few decades for unknown reasons. As children with food allergies reach school age, the issue is becoming more common in schools. For that reason, schools are now required to be prepared to take responsibility for the safety of food-allergic students. This review discusses the common problems surrounding management of food allergies in the school setting along with reasonable recommendations for addressing those problems. The most important component of food allergy management is for the student to get an accurate diagnosis and to then discuss development of an anaphylaxis action plan with their health-care provider. Each school should insist that a copy of such a plan be provided for each student with food allergy and that epinephrine is readily available should a student have an anaphylactic reaction. In addition to epinephrine, it is essential that school personnel be properly trained to recognize and treat allergic reactions should they occur. Known deficiencies in school preparedness have been documented in previous literature, and consequently, both state and the federal government have begun to implement policies to help with school preparedness.
- Stress-Induced Activation of the Sympathoadrenal System is Determined by Genetic Background in Rat Models of Tauopathy. [JOURNAL ARTICLE]
- J Alzheimers Dis 2014 Aug 21.
Stress may accelerate onset of neurodegenerative diseases in vulnerable subjects and, vice versa, neurodegeneration affects the responsiveness to stressors. We investigated the neuroendocrine response to immobilization stress in normotensive Wistar-Kyoto rats (WKY), spontaneously hypertensive rats (SHR), and transgenic rats of respective WKY and SHR strains overexpressing human truncated tau protein. Plasma levels of epinephrine, norepinephrine, and corticosterone were determined. An immobilization-induced elevation of epinephrine and norepinephrine was significantly reduced in WKY transgenic rats compared to WKY wild-type rats, while no differences were seen between SHR transgenic and SHR wild-type animals. Our data have shown that sympathoadrenal system response to stress strongly depends on both tau protein-induced neurodegeneration and genetic background of experimental animals.
- Effects of epinephrine on lidocaine pharmacokinetics and blood volume in the dental pulp. [Journal Article]
- J Endod 2014 Sep; 40(9):1370-4.
Epinephrine potentiates and prolongs the efficacy of local anesthetics by reducing blood flow. We investigated the effect of epinephrine on the pharmacokinetics of lidocaine and the pulpal blood volume after maxillary infiltration anesthesia in rats.We measured the (14)C-radioactivity and (14)C-distribution in the maxilla and the dental pulp after the injection of 2% (14)C-lidocaine with or without 10 μg/mL epinephrine (n = 7) into the palatine mucosa proximal to the first molar. The blood volume in the pulp was measured using (99m)Tc-pertechnetate (n = 5).When lidocaine was injected together with epinephrine, the lidocaine became widely distributed throughout the maxilla and was observed mainly in the first molar pulp. The lidocaine amount in the dental pulp at 10-60 minutes was more than 2 times higher than that after the injection of lidocaine alone. The relative pulpal blood volume after 20 minutes decreased to 63.1% of the value after the injection of lidocaine alone.We found that lidocaine had infiltrated into the molar pulp after infiltration anesthesia. Furthermore, our results suggested that epinephrine augmented the retention of lidocaine in the pulp.