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1.
Pediatr Allergy Immunol ; 35(7): e14192, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39007449

RESUMEN

BACKGROUND: While food allergy (FA) has been increasingly recognized as a growing public health burden worldwide, epidemiological studies on FA in Japan are limited. METHODS: This was a noninterventional, observational study using the administrative claims data from 2010 to 2019 (10 years). Patients with physician-diagnosed FA in Japan (prevalent cohort) were divided into high-risk or low-risk cohorts using adrenaline prescription. The high-risk cohort was further divided into anaphylaxis or nonanaphylaxis cohort based on the occurrence of anaphylaxis or a serious allergic reaction (SAR) during 1 year after adrenaline prescription. The primary objective was to examine yearly prevalence of FA. The secondary objectives were to describe demographics/clinical characteristics and healthcare resource utilization (HCRU), to evaluate the number of occurrences of anaphylaxis/SAR in the high-risk cohort, and the impact of anaphylaxis/SAR on HCRU. RESULTS: The overall standardized prevalence rate was 0.325% (95% confidence interval [CI], 0.311-0.339) in 2010 and 0.797% (95% CI, 0.790-0.804) in 2019 and predominant in patients age <6 years (preschool; 3.377% [95% CI, 3.229-3.525] in 2010 and 5.726% [95% CI, 5.663-5.789] in 2019). Majority of FA patients (>80%) were children/adolescent throughout the 10 years. While high-risk cohort was a relatively minor population (8.5% in the prevalent cohort in 2019), the occurrence of anaphylaxis/SAR in the high-risk cohort was 227,690/100,000 patient-years. Multivariate analysis showed a significant increase in HCRU variables in the anaphylaxis versus nonanaphylaxis cohort (e.g., 2.08 [95% CI, 2.05-2.11] times more FA-related outpatient visits). CONCLUSIONS: Prevalence of FA increased in a statistically significant way from 2010 to 2019; 1.7-fold increase was observed in patients <6 years old. Patients in the high-risk cohort appear to have suffered from frequent anaphylaxis/SAR, highlighting an unmet medical need for FA patients at "high-risk," considering the unavailability of approved medications to prevent anaphylaxis/SAR.


Asunto(s)
Anafilaxia , Hipersensibilidad a los Alimentos , Humanos , Hipersensibilidad a los Alimentos/epidemiología , Japón/epidemiología , Prevalencia , Masculino , Femenino , Preescolar , Anafilaxia/epidemiología , Niño , Lactante , Epinefrina/uso terapéutico , Estudios de Cohortes , Recién Nacido , Pueblos del Este de Asia
2.
Bull Exp Biol Med ; 177(1): 63-67, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38954300

RESUMEN

Compound L-36, a new derivative of 6H-1,3,4-thiadiazine, was studied in in vitro and in vivo experiments. This compound exhibits high antiplatelet and antithrombogenic activity. In in vitro experiments, compound L-36 by its antiplatelet activity (by IC50) was superior to acetylsalicylic acid by 9.4 times. In in vivo experiments, compound L-36 by its ED50 value was close to the comparison drug. On the model of pulmonary artery thrombosis, compound L-36 ensured better survival of experimental animals than acetylsalicylic acid. Morphological studies showed that compound L-36 effectively attenuated the thrombosis processes in the pulmonary tissue induced by intravenous injection of a thrombogenic mixture (epinephrine and collagen).


Asunto(s)
Aspirina , Fibrinolíticos , Inhibidores de Agregación Plaquetaria , Agregación Plaquetaria , Tiadiazinas , Animales , Inhibidores de Agregación Plaquetaria/farmacología , Inhibidores de Agregación Plaquetaria/química , Tiadiazinas/farmacología , Tiadiazinas/química , Fibrinolíticos/farmacología , Fibrinolíticos/química , Agregación Plaquetaria/efectos de los fármacos , Aspirina/farmacología , Masculino , Trombosis/tratamiento farmacológico , Trombosis/prevención & control , Ratas , Arteria Pulmonar/efectos de los fármacos , Colágeno , Epinefrina/farmacología , Ratones , Plaquetas/efectos de los fármacos
3.
Int J Mol Sci ; 25(13)2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-39000088

RESUMEN

Neuroendocrine tumors are uncommon in the gastrointestinal system but can develop in the majority of the body's epithelial organs. Our goal was to examine the presence and clinical application of serum dopamine (DA), serotonin (ST), norepinephrine (NE), and epinephrine (EPI), in addition to determining the significance of the Prognostic Nutritional Index (PNI), Glasgow Prognostic Score (GPS), and systemic inflammatory response (SIR) markers as a prognostic factor for patients with colorectal neuroendocrine tumors (CR-NETs), in various tumor-node-metastasis (TNM) stages. We also wanted to identify the possible connection between them. This study included 25 consecutive patients who were diagnosed with CR-NETs and a control group consisting of 60 patients with newly diagnosed colorectal cancer (CRC). We used the Enzyme-Linked Immunosorbent Assay (ELISA) technique. This study revealed that CR-NET patients showed significantly higher serum levels of DA compared to CRC patients. We showed that serum DA was present in the early stages of CR-NETs, with increasing levels as we advanced through the TNM stages. Moreover, we found a close relationship between the levels of DA and the inflammation and nutritional status of the CR-NET patients in this study. CR-NET patients from the PNI < 47.00 subgroup had a higher level of DA than those from the PNI ≥ 47.00 subgroup. Pearson's correlation analysis revealed correlations between DA, PNI, and the neutrophil/lymphocyte ratio (NLR) and the platelet/lymphocyte ratio (PLR). Both hematological indices were negatively correlated with albumin (ALB). Our investigation's findings relating to the PNI, GPS, SIR, and DA indicate that these tools can be markers of nutritional and systemic inflammatory status, are simple to use, and are repeatable. Further research on this topic could provide valuable insights into which biomarkers to incorporate into clinical practice for the management of CR-NET patients.


Asunto(s)
Neoplasias Colorrectales , Dopamina , Epinefrina , Estadificación de Neoplasias , Tumores Neuroendocrinos , Norepinefrina , Serotonina , Humanos , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/sangre , Femenino , Masculino , Persona de Mediana Edad , Tumores Neuroendocrinos/patología , Tumores Neuroendocrinos/sangre , Tumores Neuroendocrinos/diagnóstico , Serotonina/sangre , Epinefrina/sangre , Pronóstico , Norepinefrina/sangre , Anciano , Dopamina/sangre , Dopamina/metabolismo , Adulto , Biomarcadores de Tumor/sangre , Evaluación Nutricional , Neurotransmisores/sangre , Neurotransmisores/metabolismo , Inflamación/sangre , Inflamación/patología
4.
Sci Rep ; 14(1): 15738, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38977766

RESUMEN

The relationship between VISmax and mortality in patients undergoing major abdominal surgery remains unclear. This study aims to evaluate the association between VISmax and both short-term and long-term all-cause mortality in patients undergoing major abdominal surgery, VISmax was calculated (VISmax = dopamine dose [µg/kg/min] + dobutamine dose [µg/kg/min] + 100 × epinephrine dose [µg/kg/min] + 10 × milrinone dose [µg/kg/min] + 10,000 × vasopressin dose [units/kg/min] + 100 × norepinephrine dose [µg/kg/min]) using the maximum dosing rates of vasoactives and inotropics within the first 24 h postoperative ICU admission. The study included 512 patients first admitted to the intensive care unit (ICU) who were administered vasoactive drugs after major abdominal surgery. The data was extracted from the medical information mart in intensive care-IV database. VISmax was stratified into five categories: 0-5, > 5-15, > 15-30, > 30-45, and > 45. Compared to patients with the lowest VISmax (≤ 5), those with the high VISmax (> 45) had an increased risk of 30-day mortality (hazard ratio [HR] 3.73, 95% CI 1.16-12.02; P = 0.03) and 1-year mortality (HR 2.76, 95% CI 1.09-6.95; P = 0.03) in fully adjusted Cox models. The ROC analysis for VISmax predicting 30-day and 1-year mortality yielded AUC values of 0.69 (95% CI 0.64-0.75) and 0.67 (95% CI 0.62-0.72), respectively. In conclusion, elevated VISmax within the first postoperative 24 h after ICU admission was associated with increased risks of both short-term and long-term mortality in patients undergoing major abdominal surgery.


Asunto(s)
Abdomen , Vasoconstrictores , Humanos , Masculino , Femenino , Estudios Retrospectivos , Anciano , Persona de Mediana Edad , Abdomen/cirugía , Vasoconstrictores/administración & dosificación , Vasoconstrictores/uso terapéutico , Unidades de Cuidados Intensivos , Cardiotónicos/administración & dosificación , Norepinefrina , Epinefrina/administración & dosificación , Dobutamina/administración & dosificación , Dopamina , Vasopresinas , Milrinona/administración & dosificación
5.
Crit Care ; 28(1): 242, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39010134

RESUMEN

BACKGROUND: Half of pediatric in-hospital cardiopulmonary resuscitation (CPR) events have an initial rhythm of non-pulseless bradycardia with poor perfusion. Our study objectives were to leverage granular data from the ICU-RESUScitation (ICU-RESUS) trial to: (1) determine the association of early epinephrine administration with survival outcomes in children receiving CPR for bradycardia with poor perfusion; and (2) describe the incidence and time course of the development of pulselessness. METHODS: Prespecified secondary analysis of ICU-RESUS, a multicenter cluster randomized trial of children (< 19 years) receiving CPR in 18 intensive care units in the United States. Index events (October 2016-March 2021) lasting ≥ 2 min with a documented initial rhythm of bradycardia with poor perfusion were included. Associations between early epinephrine (first 2 min of CPR) and outcomes were evaluated with Poisson multivariable regression controlling for a priori pre-arrest characteristics. Among patients with arterial lines, intra-arrest blood pressure waveforms were reviewed to determine presence of a pulse during CPR interruptions. The temporal nature of progression to pulselessness was described and outcomes were compared between patients according to subsequent pulselessness status. RESULTS: Of 452 eligible subjects, 322 (71%) received early epinephrine. The early epinephrine group had higher pre-arrest severity of illness and vasoactive-inotrope scores. Early epinephrine was not associated with survival to discharge (aRR 0.97, 95%CI 0.82, 1.14) or survival with favorable neurologic outcome (aRR 0.99, 95%CI 0.82, 1.18). Among 186 patients with invasive blood pressure waveforms, 118 (63%) had at least 1 period of pulselessness during the first 10 min of CPR; 86 (46%) by 2 min and 100 (54%) by 3 min. Sustained return of spontaneous circulation was highest after bradycardia with poor perfusion (84%) compared to bradycardia with poor perfusion progressing to pulselessness (43%) and bradycardia with poor perfusion progressing to pulselessness followed by return to bradycardia with poor perfusion (62%) (p < 0.001). CONCLUSIONS: In this cohort of pediatric CPR events with an initial rhythm of bradycardia with poor perfusion, we failed to identify an association between early bolus epinephrine and outcomes when controlling for illness severity. Most children receiving CPR for bradycardia with poor perfusion developed subsequent pulselessness, 46% within 2 min of CPR onset.


Asunto(s)
Bradicardia , Reanimación Cardiopulmonar , Epinefrina , Humanos , Epinefrina/administración & dosificación , Epinefrina/uso terapéutico , Reanimación Cardiopulmonar/métodos , Reanimación Cardiopulmonar/estadística & datos numéricos , Masculino , Femenino , Bradicardia/tratamiento farmacológico , Bradicardia/terapia , Preescolar , Niño , Lactante , Adolescente , Unidades de Cuidados Intensivos/estadística & datos numéricos , Unidades de Cuidados Intensivos/organización & administración
6.
J Pak Med Assoc ; 74(7): 1397-1401, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39028090

RESUMEN

Objectives: To assess the knowledge and awareness of dental house officers regarding calculation of local anaesthesia dosage, and to evaluate differences in practices at various tertiary care facilities. METHODS: The cross-sectional study was conducted at three dental hospitals affiliated with Dow University of Health Sciences, Karachi from July to December 2022, and comprised house officers of either gender currently enrolled at the participating centres. Data was collected using a self-administered questionnaire to assess knowledge and awareness of local anaesthesia dosage calculation, administration methods, and common complications. Data was analysed using SPSS 26. RESULTS: Of the 200 subjects approached, 136(68%) responded, and 89(65.4%) of them were females. Knowledge regarding the meaning of 2% lidocaine solution was low 45(33%), and 68(50%) subjects were knowledgeable about the maximum dosage of lidocaine with epinephrine. In terms of practice, lidocaine was the most commonly administered local anaesthetic 115(85%), followed by bupivacaine 15(11%). The majority of subjects administered local anaesthesia with vasoconstrictor 127(94%), but only 36(27%) performed aspiration during administration. Syncope 71(52%) was the most commonly reported complication, followed by lip/cheek/tongue biting by 35(26%). CONCLUSIONS: House officers' knowledge level of local anaesthesia administration indicated the need for adequate training.


Asunto(s)
Anestesia Local , Anestésicos Locales , Lidocaína , Humanos , Femenino , Pakistán , Masculino , Anestésicos Locales/administración & dosificación , Estudios Transversales , Lidocaína/administración & dosificación , Anestesia Local/métodos , Adulto , Epinefrina/administración & dosificación , Conocimientos, Actitudes y Práctica en Salud , Bupivacaína/administración & dosificación , Centros de Atención Terciaria , Anestesia Dental/métodos , Encuestas y Cuestionarios , Vasoconstrictores/administración & dosificación , Competencia Clínica
7.
Pflugers Arch ; 476(8): 1263-1277, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38963545

RESUMEN

6-Cyanodopamine is a novel catecholamine released from rabbit isolated heart. However, it is not known whether this catecholamine presents any biological activity. Here, it was evaluated whether 6-cyanodopamine (6-CYD) is released from rat vas deferens and its effect on this tissue contractility. Basal release of 6-CYD, 6-nitrodopamine (6-ND), 6-bromodopamine, 6-nitrodopa, and 6-nitroadrenaline from vas deferens were quantified by LC-MS/MS. Electric-field stimulation (EFS) and concentration-response curves to noradrenaline, adrenaline, and dopamine of the rat isolated epididymal vas deferens (RIEVD) were performed in the absence and presence of 6-CYD and /or 6-ND. Expression of tyrosine hydroxylase was assessed by immunohistochemistry. The rat isolated vas deferens released significant amounts of both 6-CYD and 6-ND. The voltage-gated sodium channel blocker tetrodotoxin had no effect on the release of 6-CYD, but it virtually abolished 6-ND release. 6-CYD alone exhibited a negligible RIEVD contractile activity; however, at 10 nM, 6-CYD significantly potentiated the noradrenaline- and EFS-induced RIEVD contractions, whereas at 10 and 100 nM, it also significantly potentiated the adrenaline- and dopamine-induced contractions. The potentiation of noradrenaline- and adrenaline-induced contractions by 6-CYD was unaffected by tetrodotoxin. Co-incubation of 6-CYD (100 pM) with 6-ND (10 pM) caused a significant leftward shift and increased the maximal contractile responses to noradrenaline, even in the presence of tetrodotoxin. Immunohistochemistry revealed the presence of tyrosine hydroxylase in both epithelial cell cytoplasm of the mucosae and nerve fibers of RIEVD. The identification of epithelium-derived 6-CYD and its remarkable synergism with catecholamines indicate that epithelial cells may regulate vas deferens smooth muscle contractility.


Asunto(s)
Dopamina , Contracción Muscular , Conducto Deferente , Masculino , Animales , Conducto Deferente/efectos de los fármacos , Conducto Deferente/metabolismo , Conducto Deferente/fisiología , Contracción Muscular/efectos de los fármacos , Ratas , Dopamina/metabolismo , Dopamina/farmacología , Ratas Wistar , Norepinefrina/farmacología , Norepinefrina/metabolismo , Músculo Liso/efectos de los fármacos , Músculo Liso/metabolismo , Músculo Liso/fisiología , Estimulación Eléctrica , Epinefrina/farmacología , Tirosina 3-Monooxigenasa/metabolismo
8.
Bull Exp Biol Med ; 177(1): 57-62, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38954299

RESUMEN

We studied the effect of Refralon on the electrophysiological properties of the supraventricular myocardium against the background of adrenergic (epinephrine) influence in the zone of the pulmonary veins, the area where 50-90% of atrial arrhythmias is triggered. The experiments were carried out on isolated tissue preparations of Wistar rats. The multichannel microelectrode array technique was used to record action potentials simultaneously in the atrium and in the ostium and distal parts of the pulmonary veins. Epinephrine application (12-50 nM) led to depolarization of the resting potential and the conduction block in the distal part of the pulmonary veins. Refralon (30 µg/kg) restored the resting potential in the distal part of the pulmonary veins. Against the background of epinephrine, Refralon did not significantly change the duration of the action potential at 90% repolarization in comparison with control. At the same time, the comparison drug E-4031 against the background of epinephrine significantly increased the duration of action potential in the atrium and in the ostium of the pulmonary veins, and sotalol increased it only in the ostium. Neither E-4031, nor sotalol restored conduction in their distal part. Refralon has a biphasic effect under conditions of adrenergic stimulation: the fast component is responsible for stabilizing the resting potential in the pulmonary vein and reduces the dispersion of action potential duration in the atrium and pulmonary vein and is also quickly washed away, and the slow component is responsible for the increase of the action potential duration and is slowly washed away.


Asunto(s)
Potenciales de Acción , Antiarrítmicos , Epinefrina , Atrios Cardíacos , Venas Pulmonares , Ratas Wistar , Animales , Ratas , Epinefrina/farmacología , Potenciales de Acción/efectos de los fármacos , Antiarrítmicos/farmacología , Venas Pulmonares/efectos de los fármacos , Masculino , Atrios Cardíacos/efectos de los fármacos , Atrios Cardíacos/fisiopatología , Arritmias Cardíacas/fisiopatología , Arritmias Cardíacas/tratamiento farmacológico
9.
Int J Mol Sci ; 25(13)2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-39000139

RESUMEN

Epinephrine influences the function of pancreatic ß-cells, primarily through the α2A-adrenergic receptor (α2A-AR) on their plasma membrane. Previous studies indicate that epinephrine transiently suppresses insulin secretion, whereas prolonged exposure induces its compensatory secretion. Nonetheless, the impact of epinephrine-induced α2A-AR signaling on the survival and function of pancreatic ß-cells, particularly the impact of reprogramming after their removal from sustained epinephrine stimulation, remains elusive. In the present study, we applied MIN6, a murine insulinoma cell line, with 3 days of high concentration epinephrine incubation and 2 days of standard incubation, explored cell function and activity, and analyzed relevant regulatory pathways. The results showed that chronic epinephrine incubation led to the desensitization of α2A-AR and enhanced insulin secretion. An increased number of docked insulin granules and impaired Syntaxin-2 was found after chronic epinephrine exposure. Growth curve and cell cycle analyses showed the inhibition of cell proliferation. Transcriptome analysis showed the occurrence of endoplasmic reticulum stress (ER stress) and oxidative stress, such as the presence of BiP, CHOP, IRE1, ATF4, and XBP, affecting cellular endoplasmic reticulum function and survival, along with UCP2, OPA1, PINK, and PRKN, associated with mitochondrial dysfunction. Consequently, we conclude that chronic exposure to epinephrine induces α2A-AR desensitization and leads to ER and oxidative stress, impairing protein processing and mitochondrial function, leading to modified pancreatic ß-cell secretory function and cell fate.


Asunto(s)
Estrés del Retículo Endoplásmico , Epinefrina , Células Secretoras de Insulina , Insulina , Estrés Oxidativo , Animales , Epinefrina/farmacología , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Ratones , Estrés del Retículo Endoplásmico/efectos de los fármacos , Insulina/metabolismo , Secreción de Insulina/efectos de los fármacos , Receptores Adrenérgicos alfa 2/metabolismo , Receptores Adrenérgicos alfa 2/genética , Retículo Endoplásmico/metabolismo , Retículo Endoplásmico/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos
10.
Int J Circumpolar Health ; 83(1): 2367273, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38875453

RESUMEN

It has previously been shown that EpiPen® autoinjectors are likely to activate normally following up to five excursions to -25°C but data about the post-freezing performance of other brands of adrenaline autoinjectors has not previously been published. Additionally, conditions experienced by polar medics may be substantially colder than this and the performance of adrenaline autoinjectors following more extreme freeze-thaw cycles remains uncharacterised. Investigators in Antarctica and the United Kingdom performed laboratory testing on two brands of adrenaline autoinjector, EpiPen® and Jext® (12 devices of each type). A single freeze-thaw cycle involved freezing the device to -80°C then allowing it to come to room temperature. Devices were exposed to 0, 1, 5 or 15 freeze-thaw cycles. The mass of liquid ejected from each device, when activated, was then measured. No significant differences in the mass of the liquid ejected was found between the test groups. Multiple freeze-thaw cycles to -80°C are unlikely to significantly impact the amount of adrenaline solution expelled from EpiPen® and EpiPen® autoinjectors. This preliminary finding encourages further work investigating the safety and effectiveness of adrenaline autoinjectors after exposure to very low temperatures. This information would be valuable for future polar medics planning and delivering medical provision in extreme environments.


Asunto(s)
Frío , Epinefrina , Congelación , Epinefrina/administración & dosificación , Humanos , Inyecciones Intramusculares/instrumentación
11.
Arch Pediatr ; 31(5): 299-305, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38853084

RESUMEN

AIM: The aim of the study was to assess the impact of a video training program (VTP) on primary school teachers' skills in using an adrenaline auto-injector (AAI), in correlation with knowledge regarding allergies, in cases of anaphylaxis. METHODS: A questionnaire on teachers' knowledge of allergies and on their level of confidence in using an AAI was distributed in primary schools in the French department of Manche (2173 teachers). A VTP followed this questionnaire. A second questionnaire was then distributed. Theoretical knowledge was assessed with a score out of 20. The confidence level was rated on a scale from 1 to 4. RESULTS: We collected 218 responses to the first questionnaire (10.0 % of the population included). The response rate to the second questionnaire was 4.7 % (103 participants), and from this group, 93 of the 103 participants viewed the video (90.3 %). Overall, 76 of the 218 (34.9 %) participants who completed the first questionnaire also completed the second questionnaire and watched the VTP. The number of participants who completed the whole survey was 76 (out of 2173, 3.5 %). The VTP significantly improved teachers' knowledge of the subject of allergies (the average score increased by 2.11 points, p < 0.001) as well as their confidence in recognizing the signs of a severe allergic reaction and in using an AAI: 85.4 % (n = 88) of self-confident teachers after the VTP versus 42.3 % (n = 92) before the VTP (p < 0.001). CONCLUSION: The VTP improved teachers' level of knowledge and confidence in using an AAI in cases of anaphylaxis. A similar VTP could be circulated more widely in schools to offer easy access to training tools about allergies.


Asunto(s)
Anafilaxia , Epinefrina , Conocimientos, Actitudes y Práctica en Salud , Maestros , Humanos , Epinefrina/administración & dosificación , Femenino , Encuestas y Cuestionarios , Francia , Masculino , Grabación en Video , Hipersensibilidad , Adulto , Formación del Profesorado/métodos , Inyecciones Intramusculares/instrumentación , Inyecciones Intramusculares/métodos , Autoadministración
12.
Bull Exp Biol Med ; 176(6): 747-750, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38888651

RESUMEN

In in vitro model of short-term therapeutic inhalation of Xe/O2 mixture, xenon in millimolar concentrations led to a pronounced decrease in induced platelet aggregation in the platelet-enriched blood plasma. The maximum and statistically significant decrease occurred in response to induction by collagen (by ≈30%, p≤0.01) and ADP (by ≈25%, p≤0.01). A slightly weaker but statistically significant reduction in aggregation appeared in response to ristocetin (by ≈12%, p≤0.01) and epinephrine (by ≈9%, p≤0.01). It should be noted that the spontaneous aggregation exceeded the reference values in the control group. Nevertheless, even at minimal absolute values, spontaneous platelet aggregation decreased by 2 times in response to xenon (p≤0.01). The reasons for the decrease of spontaneous and induced aggregation are xenon accumulation in the lipid bilayer of the membrane with subsequent nonspecific (mechanical) disassociation of membrane platelet structures and specific block of its distinct from neuronal NMDA receptor.


Asunto(s)
Agregación Plaquetaria , Xenón , Xenón/farmacología , Agregación Plaquetaria/efectos de los fármacos , Humanos , Plaquetas/efectos de los fármacos , Plaquetas/metabolismo , Adenosina Difosfato/farmacología , Inhibidores de Agregación Plaquetaria/farmacología , Plasma Rico en Plaquetas/metabolismo , Epinefrina/farmacología , Epinefrina/sangre , Colágeno/metabolismo
13.
Bull Exp Biol Med ; 176(6): 761-766, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38896318

RESUMEN

A number of pharmacological drugs have side effects that contribute to the occurrence of atrial fibrillation, the most common type of cardiac rhythm disorders. The clinical use of antihistamines is widespread; however, information regarding their anti- and/or proarrhythmic effects is contradictory. In this work, we studied the effects and mechanisms of the potential proarrhythmic action of the first-generation antihistamine chloropyramine (Suprastin) in the atrial myocardium and pulmonary vein (PV) myocardial tissue. In PV, chloropyramine caused depolarization of the resting potential and led to reduction of excitation wave conduction. These effects are likely due to suppression of the inward rectifier potassium current (IK1). In presence of epinephrine, chloropyramine induced spontaneous automaticity in the PV and could not be suppressed by atrial pacing. Chloropyramine change functional characteristics of PV and contribute to occurrence of atrial fibrillation. It should be noted that chloropyramine does not provoke atrial tachyarrhythmias, but create conditions for their occurrence during physical exercise and sympathetic stimulation.


Asunto(s)
Fibrilación Atrial , Venas Pulmonares , Venas Pulmonares/efectos de los fármacos , Venas Pulmonares/fisiopatología , Animales , Fibrilación Atrial/fisiopatología , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/inducido químicamente , Atrios Cardíacos/efectos de los fármacos , Atrios Cardíacos/fisiopatología , Clorfeniramina/farmacología , Epinefrina/farmacología , Antagonistas de los Receptores Histamínicos H1/farmacología , Miocardio/metabolismo , Miocardio/patología , Masculino , Potenciales de Acción/efectos de los fármacos , Sistema de Conducción Cardíaco/efectos de los fármacos , Sistema de Conducción Cardíaco/fisiopatología
14.
J Cardiovasc Pharmacol ; 84(1): 110-117, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38922579

RESUMEN

ABSTRACT: Hypercatecholaminergic conditions are known to cause heart failure and cardiac fibrosis when severe. Although previous investigations have studied the effects of beta-blockade in experimental models of catecholaminergic states, the detailed benefits of beta-blockade in more realistic models of hyper-adrenergic states were less clear. In this study, we examined acute cardiac changes in rats with hyperacute catecholamine-induced heart failure with and without propranolol treatment. Male Sprague-Dawley rats (n = 12) underwent a 6-hour infusion of epinephrine and norepinephrine alone, with an additional propranolol bolus (1 mg/kg) at hour 1 (n = 6). Cardiac tissues were examined after 6 hours. Cardiac immunohistochemistry revealed significantly decreased expression of phosphorylated p-38 (left ventricle, P = 0.021; right ventricle, P = 0.021), with upregulation of reactive oxidative species and other profibrosis proteins, after catecholamine infusion alone. After 1 propranolol 1 mg/kg bolus, the levels of phosphorylated-p38 returned to levels comparable with sham (left ventricle, P = 0.021; right ventricle, P = 0.043), with additional findings including downregulation of the apoptotic pathway and profibrotic proteins. We conclude that catecholamine-induced heart failure exerts damage through the p-38 mitogen-activated protein kinase pathway and demonstrates profibrotic changes mediated by matrix metalloproteinase 9, alpha-smooth muscle actin, and fibroblast growth factor 23. Changes in these pathways attenuated acute catecholamine-induced heart failure after propranolol bolus 1 mg/kg. We conclude that propranolol bolus at 1 mg/kg is able to mediate the effects of catecholamine excess through the p-38 mitogen-activated protein kinase pathway, profibrosis, and extrinsic apoptosis pathway.


Asunto(s)
Antagonistas Adrenérgicos beta , Fibrosis , Insuficiencia Cardíaca , Norepinefrina , Propranolol , Ratas Sprague-Dawley , Proteínas Quinasas p38 Activadas por Mitógenos , Animales , Masculino , Propranolol/farmacología , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Ratas , Antagonistas Adrenérgicos beta/farmacología , Antagonistas Adrenérgicos beta/administración & dosificación , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/metabolismo , Insuficiencia Cardíaca/patología , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/inducido químicamente , Norepinefrina/metabolismo , Epinefrina/toxicidad , Epinefrina/administración & dosificación , Fosforilación , Apoptosis/efectos de los fármacos , Modelos Animales de Enfermedad , Miocardio/patología , Miocardio/metabolismo , Miocardio/enzimología , Catecolaminas/metabolismo , Especies Reactivas de Oxígeno/metabolismo
15.
Microcirculation ; 31(5): e12858, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38837563

RESUMEN

OBJECTIVE: The sympathetic-parasympathetic (or axo-axonal) interaction mechanism mediated that neurogenic relaxation, which was dependent on norepinephrine (NE) releases from sympathetic nerve terminal and acts on ß2-adrenoceptor of parasympathetic nerve terminal, has been reported. As NE is a weak ß2-adrenoceptor agonist, there is a possibility that synaptic NE is converted to epinephrine by phenylethanolamine-N-methyltransferase (PNMT) and then acts on the ß2-adrenoceptors to induce neurogenic vasodilation. METHODS: Blood vessel myography technique was used to measure relaxation and contraction responses of isolated basilar arterial rings of rats. RESULTS: Nicotine-induced relaxation was sensitive to propranolol, guanethidine (an adrenergic neuronal blocker), and Nω-nitro-l-arginine. Nicotine- and exogenous NE-induced vasorelaxation was partially inhibited by LY-78335 (a PNMT inhibitor), and transmural nerve stimulation depolarized the nitrergic nerve terminal directly and was not inhibited by LY-78335; it then induced the release of nitric oxide (NO). Epinephrine-induced vasorelaxation was not affected by LY-78335. However, these vasorelaxations were completely inhibited by atenolol (a ß1-adrenoceptor antagonist) combined with ICI-118,551 (a ß2-adrenoceptor antagonist). CONCLUSIONS: These results suggest that NE may be methylated by PNMT to form epinephrine and cause the release of NO and vasodilation. These results provide further evidence supporting the physiological significance of the axo-axonal interaction mechanism in regulating brainstem vascular tone.


Asunto(s)
Nicotina , Feniletanolamina N-Metiltransferasa , Vasodilatación , Animales , Vasodilatación/efectos de los fármacos , Feniletanolamina N-Metiltransferasa/metabolismo , Ratas , Nicotina/farmacología , Masculino , Norepinefrina/farmacología , Arterias Cerebrales/efectos de los fármacos , Óxido Nítrico/metabolismo , Ratas Sprague-Dawley , Receptores Adrenérgicos beta 2/metabolismo , Epinefrina/farmacología
16.
Cells ; 13(12)2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38920675

RESUMEN

BACKGROUND: Ischemic post-conditioning (IPoC) has been shown to improve outcomes in limited pre-clinical models. As down-time is often unknown, this technique needs to be investigated over a range of scenarios. As this tool limits reperfusion injury, there may be limited benefit or even harm after short arrest and limited ischemia-reperfusion injury. METHODS: Eighteen male Wistar rats underwent 7 min of asphyxial arrest. Animals randomized to IPoC received a 20 s pause followed by 20 s of compressions, repeated four times, initiated 40 s into cardiopulmonary resuscitation. If return of spontaneous circulation (ROSC) was achieved, epinephrine was titrated to mean arterial pressure (MAP) of 70 mmHg. Data were analyzed using t-test or Mann-Whitney test. Significance set at p ≤ 0.05. RESULTS: The rate of ROSC was equivalent in both groups, 88%. There was no statistically significant difference in time to ROSC, epinephrine required post ROSC, carotid flow, or peak lactate at any timepoint. There was a significantly elevated MAP with IPoC, 90.7 mmHg (SD 13.9), as compared to standard CPR, 76.7 mmHg (8.5), 2 h after ROSC, p = 0.03. CONCLUSIONS: IPoC demonstrated no harm in a model of short arrest using a new arrest etiology for CPR based IPoC intervention in a rat model.


Asunto(s)
Asfixia , Modelos Animales de Enfermedad , Paro Cardíaco , Poscondicionamiento Isquémico , Ratas Wistar , Animales , Paro Cardíaco/terapia , Paro Cardíaco/complicaciones , Paro Cardíaco/fisiopatología , Masculino , Poscondicionamiento Isquémico/métodos , Ratas , Asfixia/complicaciones , Reanimación Cardiopulmonar/métodos , Epinefrina
17.
Arerugi ; 73(4): 340-346, 2024.
Artículo en Japonés | MEDLINE | ID: mdl-38880633

RESUMEN

BACKGROUND: Although paramedics can use adrenaline autoinjectors (AAIs) during their duties, the actual conditions of their use and the challenges faced remain unclear. We investigated the actual situation and issues pertaining to creating an environment in which paramedics can operate AAIs more effectively. METHODS: A web-based survey was conducted among paramedics who participated in a web-based training session related to their latest knowledge on food allergies and emergency responses in 2022. The survey items included practice and training environments, practices of AAI administration, and regarding AAI administration. RESULTS: Seventy paramedics responded to the survey. Twenty-eight respondents (40%) had experienced cases in which they wished they had an AAI in their work to date, but only one had actually administered one. Thirty-four (49%) indicated that it would be good to have an AAI in the ambulance at all times; 48 (69%) were not concerned about the use of AAI, and the level of concern about its use was significantly related to length of service. The study also revealed that paramedics do not have an adequate training environment regarding AAI. CONCLUSION: Few paramedics have experience in administering AAI, although they are aware of the need for it. For more effective use of AAI, it is necessary to establish a training environment to familiarize paramedics with anaphylaxis and an environment that enables them to use AAI promptly in the field.


Asunto(s)
Técnicos Medios en Salud , Anafilaxia , Epinefrina , Epinefrina/administración & dosificación , Humanos , Técnicos Medios en Salud/educación , Anafilaxia/tratamiento farmacológico , Encuestas y Cuestionarios , Adulto , Femenino , Masculino , Persona de Mediana Edad , Paramédico
18.
Int J Cardiol ; 410: 132228, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38844092

RESUMEN

BACKGROUND: no-reflow can complicate up to 25% of pPCI and is associated with significant morbidity and mortality. We aimed to compare the outcomes of intracoronary epinephrine and verapamil with intracoronary adenosine in the treatment of no-reflow after primary percutaneous coronary intervention (pPCI). METHODS: 108 STEMI patients had no-reflow during pPCI were assigned into four groups. Group 1, in which epinephrine and verapamil were injected through a well-cannulated guiding catheter. Group 2, in which same drugs were injected in the distal coronary bed through a microcatheter or perfusion catheter. Group 3, in which adenosine was injected through a guiding catheter. Group 4, in which adenosine was injected in distal coronary bed. Primary end point was the achievement of TIMI III flow and MBG II or III. Secondary end point was major adverse cardiovascular and cerebrovascular events (MACCEs) during hospital stay. RESULTS: The study groups did not differ in their baseline characteristics. Primary end point was achieved in 15 (27.8%) patients in the guide-delivery arm compared with 34 (63%) patients in the local-delivery arm, p < 0.01. However, the primary end point did not differ between the epinephrine/verapamil group and the adenosine group (27 (50%) vs 22 (40.7%), p = 0.334). The secondary end points were similar between the study groups. CONCLUSION: Local delivery of epinephrine, verapamil and adenosine in the distal coronary bed is more effective in achieving TIMI III flow with MBG II or III compared with their guide-delivery in patients who suffered no-reflow during pPCI. There was no difference between epinephrine/verapamil Vs. adenosine.


Asunto(s)
Adenosina , Epinefrina , Fenómeno de no Reflujo , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Verapamilo , Humanos , Verapamilo/administración & dosificación , Masculino , Femenino , Adenosina/administración & dosificación , Epinefrina/administración & dosificación , Persona de Mediana Edad , Intervención Coronaria Percutánea/métodos , Fenómeno de no Reflujo/etiología , Fenómeno de no Reflujo/tratamiento farmacológico , Infarto del Miocardio con Elevación del ST/tratamiento farmacológico , Infarto del Miocardio con Elevación del ST/terapia , Infarto del Miocardio con Elevación del ST/cirugía , Anciano , Vasodilatadores/administración & dosificación , Resultado del Tratamiento , Estudios Prospectivos
19.
Pediatr Allergy Immunol Pulmonol ; 37(2): 56-59, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38864768

RESUMEN

Background: Povidone, a synthetic polymer commonly used in various products such as antiseptics, cosmetics, and medications, has been associated with allergic reactions, including anaphylaxis. Despite its widespread use, cases of povidone-induced anaphylaxis, especially in children, are under-recognized. This case report aims to highlight the importance of considering povidone allergy in pediatric patients presenting with anaphylaxis. Case Presentation: We describe a 3-year-old boy who experienced anaphylaxis following the application of povidone-iodine antiseptic solution to a leg wound. He presented with generalized urticaria, angioedema, dyspnea, and cough. Prompt diagnosis and management were initiated in the emergency department. He experienced the second anaphylaxis with povidone-containing eye drops prescribed during an ophthalmology visit. Conclusions: Povidone allergy should be considered in pediatric patients presenting with anaphylaxis, especially those with idiopathic reactions or multiple drug allergies. Clinicians should emphasize patient education on label reading and the provision of adrenaline autoinjectors to prevent life-threatening reactions associated with povidone exposure.


Asunto(s)
Anafilaxia , Antiinfecciosos Locales , Povidona Yodada , Humanos , Anafilaxia/inducido químicamente , Anafilaxia/diagnóstico , Masculino , Preescolar , Povidona Yodada/efectos adversos , Povidona Yodada/administración & dosificación , Antiinfecciosos Locales/efectos adversos , Antiinfecciosos Locales/administración & dosificación , Hipersensibilidad a las Drogas/diagnóstico , Hipersensibilidad a las Drogas/etiología , Epinefrina/administración & dosificación , Epinefrina/efectos adversos , Soluciones Oftálmicas/efectos adversos
20.
Anal Chem ; 96(24): 9969-9974, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38847356

RESUMEN

Epinephrine (EP) is an essential catecholamine in the human body. Currently, most EP detection methods are not suitable for in vivo detection due to material limitations. An organic small molecule fluorescent probe based on a chemical cascade reaction for the detection of EP was designed. Anionic heptamethine cyanine dye was selected as a fluorescent dye because of its NIR fluorescence emission with excellent biocompatibility. The secondary amine of EP nucleophilically attacks the carbonate of the probe with its stronger nucleophilicity and further undergoes intramolecular nucleophilic cyclization to release the fluorophore. Other substances containing only primary amines or no ß-OH lack reaction competitiveness due to their weaker nucleophilicity or inability to undergo further cyclization. The fluorescence recovery of the probe was linearly related to the EP concentration of 2-75 µmol/L. The detection limit was 0.4 µmol/L. The recovery rate was 94.78-111.32%. Finally, we successfully achieved bioimaging of EP in living cells and EP analogue in nematodes.


Asunto(s)
Carbocianinas , Epinefrina , Colorantes Fluorescentes , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Humanos , Epinefrina/análisis , Carbocianinas/química , Animales , Imagen Óptica , Aniones/química , Aniones/análisis , Caenorhabditis elegans , Límite de Detección , Rayos Infrarrojos , Células HeLa , Estructura Molecular
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