- Assessment of 'on-treatment platelet reactivity' and relationship with cerebral micro-embolic signals in asymptomatic and symptomatic carotid stenosis. [Journal Article]
- JNJ Neurol Sci 2017 May 15; 376:133-139
- CONCLUSIONS: Carotid interventional treatment, presumably in combination with resolution of the acute phase response, may decrease the prevalence of HTPR in patients with recently symptomatic carotid stenosis over time. Preliminary subgroup analysis suggests that successful intervention may reduce the prevalence of aspirin-HTPR in symptomatic patients to lower levels than asymptomatic medically-treated patients on aspirin monotherapy. Larger, longitudinal studies are warranted to reassess the impact of more intensive secondary preventive treatment on ex vivo platelet function at different levels of shear stress in carotid stenosis patients.
- Central Nervous System GLP-1 Receptors Regulate Islet Hormone Secretion and Glucose Homeostasis in Male Rats. [Journal Article]
- EEndocrinology 2017 Apr 18
- The glucagon-like peptide 1 (GLP-1) system plays an important role in blood glucose regulation, in great part through coordinate control of insulin and glucagon secretion. These effects are generally...
The glucagon-like peptide 1 (GLP-1) system plays an important role in blood glucose regulation, in great part through coordinate control of insulin and glucagon secretion. These effects are generally attributed to GLP-1 produced in peripheral sites, principally the intestine. GLP-1 is also produced in hindbrain neurons that signal through GLP-1 receptors (GLP-1r) expressed in brain regions involved in metabolic regulation. GLP-1 in the central nervous system (CNS) induces satiety, visceral illness, and stress responses. However, recent evidence suggests CNS GLP-1 is also involved in glucose regulation. To test the hypothesis that central GLP-1 regulates islet hormone secretion, conscious rats were given intra-cerebroventricular (i.c.v.): a) GLP-1, b) GLP-1r antagonist exendin-[9-39] (Ex-9), or c) saline during fasting or hyperglycemia from intravenous (IV) glucose. Administration of CNS GLP-1 increased fasting glucose, glucagon, corticosterone and epinephrine and blunted insulin secretion in response to hyperglycemia. Paradoxically, GLP-1r blockade with i.c.v. Ex-9 also reduced glucose-stimulated insulin secretion, and administration of i.c.v. Ex-9 to freely feeding rats caused mild glucose intolerance. Thus, direct administration of CNS GLP-1 affected islet hormone secretion counter to what is seen with peripherally administered GLP-1, an effect likely due to stimulation of sympathetic nervous system activity. In contrast, blockade of brain GLP-1r supports a role for CNS GLP-1 on glucose-stimulated insulin secretion and glucose control after a meal. These findings suggest a model in which activation of CNS GLP-1r by endogenous peptide promotes glucose tolerance, an effect that can be over-ridden by stress responses stimulated by exogenous GLP-1.
- Synthesis of Dopamine in E.coli Using Plasmid Based Expression System and Its Marked Effect on Host Growth Profiles. [Journal Article]
- PBPrep Biochem Biotechnol 2017 Apr 21
- L-Dopa and dopamine are important pathway intermediates towards the synthesis of catecholamine like epinephrine and norepinephrine from amino acid L-tyrosine. Dopamine, secreted from dopaminergic ner...
L-Dopa and dopamine are important pathway intermediates towards the synthesis of catecholamine like epinephrine and norepinephrine from amino acid L-tyrosine. Dopamine, secreted from dopaminergic nerve cells, serves as an important neurotransmitter. We report the synthesis of dopamine by extending the aromatic amino acid pathway of E.coli DH5α by expression of 4-hydroxyphenylacetate-3-hydrolase (HpaBC) from E.coli and an engineered dopa decarboxylase (DDC) from pig kidney cell. The activity of HpaBC and DDC require 200 µM iron supplementation and 50 µM vitamin B6 respectively as additives to the growth media. The maximum concentration of L-Dopa and dopamine obtained from the broth was around 26 mg/L and 27 mg/L after 24 hours of separate shake flask studies. We observed that in presence of dopamine synthesized in vivo host growth was remarkably enhanced. These observations lead us to an interesting finding about the role of these catecholamines on bacterial growth. It is clear that synthesis of dopamine in vivo actually promotes growth much efficiently as compared to when dopamine is added to the system from outside. From HPLC and GC-MS data it was further observed that L-Dopa was stable within the observable time of experiments while dopamine actually was subjected to degradation via oxidation and host consumption.
- Emerging Approaches to Food Desensitization in Children. [Review]
- CACurr Allergy Asthma Rep 2017; 17(5):32
- The purpose of this review is to highlight the recent advances in food desensitization in children with food allergy.
The purpose of this review is to highlight the recent advances in food desensitization in children with food allergy.
- Metabolomics of fescue toxicosis in grazing beef steers. [Journal Article]
- FCFood Chem Toxicol 2017 Apr 18
- Fescue toxicosis (FT) results from consumption of tall fescue (Lolium arundinaceum) infected with an endophyte (Epichloë coenophiala) that produces ergot alkaloids (EA), which are considered key etio...
Fescue toxicosis (FT) results from consumption of tall fescue (Lolium arundinaceum) infected with an endophyte (Epichloë coenophiala) that produces ergot alkaloids (EA), which are considered key etiological agents of FT. Decreased weight gains, hormonal imbalance, circulating cholesterol disruption, and decreased volatile fatty acid absorption suggest toxic (E+) fescue-induced metabolic perturbations. Employing untargeted high-resolution metabolomics (HRM) to analyze E+ grazing-induced plasma and urine metabolome changes, fescue-naïve Angus steers were placed on E+ or non-toxic (Max-Q) fescue pastures and plasma and urine were sampled before, 1, 2, 14, and 28 days after pasture assignment. Plasma and urine catecholamines and urinary EA concentrations were also measured. In E+ steers, urinary EA appeared early and peaked at 14 days. 13,090 urinary and 20,908 plasma HRM features were detected; the most significant effects were observed earlier (2 days) in the urine and later (>14 days) in the plasma. Alongside EA metabolite detection, tryptophan and lipid metabolism disruption were among the main consequences of E+ consumption. The E+ grazing-associated metabolic pathways and signatures described herein may accelerate development of novel early FT detection and treatment strategies.
- Disaggregation Following Agonist-Induced Platelet Activation in Patients on Dual Antiplatelet Therapy. [Journal Article]
- JCJ Cardiovasc Transl Res 2017 Apr 19
- Disaggregation as the difference between maximal and final platelet aggregation by light transmission aggregometry indicates the stability of platelet aggregates. We evaluated the extent of disaggreg...
Disaggregation as the difference between maximal and final platelet aggregation by light transmission aggregometry indicates the stability of platelet aggregates. We evaluated the extent of disaggregation after platelet stimulation with adenosine diphosphate (ADP), arachidonic acid (AA), collagen, epinephrine, and thrombin receptor-activating peptide (TRAP)-6 in 323 patients on dual antiplatelet therapy with daily aspirin and clopidogrel (group 1), prasugrel (group 2), or ticagrelor (group 3) therapy. All patients in group 1 underwent elective angioplasty and stenting, whereas all patients included in groups 2 and 3 suffered from acute coronary syndromes (STEMI or NSTEMI) and underwent urgent PCI. Significant differences between maximal and final platelet aggregation were observed with all agonists throughout the groups (all p<0.001). Disaggregation was highest using AA (clopidogrel 36.5%; prasugrel/ticagrelor 100%) and ADP (clopidogrel 21.7%; prasugrel/ticagrelor 100%). In contrast, low disaggregation was observed after platelet stimulation with collagen and TRAP-6 in clopidogrel-treated patients, and after platelet stimulation with collagen and epinephrine in prasugrel- and ticagrelor-treated patients. In conclusion, pathways of platelet activation that are not inhibited by standard antiplatelet therapy allow persisting platelet aggregation and may at least in part be responsible for adverse ischemic events.
- β- and α2-Adrenoceptor Control of Vascular Tension and Catecholamine Release in Female Normotensive and Spontaneously Hypertensive Rats. [Journal Article]
- FNFront Neurol 2017; 8:130
- As in humans, young, female, spontaneously hypertensive rats (SHR) have a lower blood pressure than male SHR. In male, normotensive rats (WKY), α2- and β1+2-adrenoceptors (AR) reciprocally controlled...
As in humans, young, female, spontaneously hypertensive rats (SHR) have a lower blood pressure than male SHR. In male, normotensive rats (WKY), α2- and β1+2-adrenoceptors (AR) reciprocally controlled catecholamine release and vascular smooth muscle tension. This interaction was malfunctioning in male SHR. The present study analyzed if a favorable shift in the α2/β1+2AR interaction may represent an antihypertensive protection in females. Female SHR (early hypertension, 12-14 weeks) and age-matched WKY were infused with tyramine (15 min) to stimulate norepinephrine (NE) release through the reuptake transporter, consequently preventing reuptake. Presynaptic control of vesicular release was therefore reflected as differences in overflow to plasma. The released NE increased total peripheral vascular resistance (TPR). The results showed that β1>2AR facilitated tyramine-stimulated NE release in both strains, also in the presence of α2AR-antagonist (L-659,066). βAR-antagonist (atenolol-β1, ICI-118551-β2, nadolol-β1+2) had no effect on the increased secretion of epinephrine after L-659,066 in WKY, but β1>2AR-antagonist augmented the L-659,066-induced increase in the secretion of epinephrine in SHR. Nadolol increased the TPR response to tyramine with a greater effect in WKY than SHR, whereas β1or2-selective antagonists did not. One βAR-subtype may therefore substitute for the other. When both β1+2AR were blocked, α2AR-antagonist still reduced the TPR response in WKY but not SHR. Thus, α2/β1+2AR reciprocally controlled catecholamine release, with a particular negative β1AR-influence on α2AR-auto-inhibition of epinephrine secretion in SHR. Moreover, in these female rats, β1/2AR-independent α2AR-mediated vasoconstriction was seen in WKY but not SHR, but β1/2AR-mediated vasodilation downregulated adrenergic vasoconstriction, not only in WKY but also in SHR.
- Systematic review with network meta-analysis: dual therapy for high-risk bleeding peptic ulcers. [Journal Article]
- BGBMC Gastroenterol 2017 Apr 19; 17(1):55
- CONCLUSIONS: Mechanical therapy was the most appropriate modality to add to epinephrine injection. Epinephrine plus thermal coagulation was effective for controlling high risk bleeding ulcers. There was no further benefit with sclerosants with regard to rebleeding or surgery, and sclerosants were also associated with more adverse events than any other modality.
- To Give Epinephrine or Not to Give Epinephrine-That Is (No Longer) The Question! [Journal Article]
- NSNASN Sch Nurse 2017; 32(3):162-164
- It is vital that school nurses be able to assess students who are at risk for anaphylaxis and that nurses train school staff to identify the symptoms of a life-threatening allergic reaction. When a r...
It is vital that school nurses be able to assess students who are at risk for anaphylaxis and that nurses train school staff to identify the symptoms of a life-threatening allergic reaction. When a reaction occurs, school nurses and staff must be prepared to administer epinephrine immediately.
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- The management of ventricular dysrhythmia in aconite poisoning. [Journal Article]
- CTClin Toxicol (Phila) 2017; 55(5):313-321
- CONCLUSIONS: Based on the evidence available from human case reports, flecainaide or amiodarone appear to be more associated with a return to sinus rhythm than lidocaine and/or cardioversion, although it is not established whether the administration of treatment caused reversion to normal sinus rhythm. The potential beneficial effects of amiodarone were not observed in animal studies. This may be due to intra-species differences between ion channels or relate to the wider cardiovascular toxicity of aconite that extends beyond arrhythmias. Prolonged cardiopulmonary resuscitation and cardiopulmonary bypass should be considered as an integral part of good clinical care as "time-buying" strategies to allow the body to excrete the toxic alkaloids. There may also be a role for mexiletine, procainamide and magnesium sulphate.