Association of Advanced Airway Management in Preference to Intravenous Adrenaline on Neurological Outcomes Following Out-of-Hospital Cardiac Arrest.

AIM: To examine the preference for advanced airway management (AAM) or intravenous adrenaline administration (IVAd) provided by emergency medical services (EMS) for out-of-hospital cardiac arrest (OHCA) with shockable or nonshockable rhythms. METHODS: We conducted a retrospective analysis of a nationwide cohort of OHCA patients in Japan. Adult patients with witnessed collapse who were provided AAM and/or IVAd by EMS between June 2014 and December 2019 were divided into the AAM preferred group and IVAd preferred group, according to the initial advanced EMS intervention. The rates of favorable neurological outcomes (cerebral performance category 1 or 2 after 30 days) were compared between groups of patients with initial shockable or nonshockable rhythms. RESULTS: We analyzed 1365 and 9733 patients with initial shockable and nonshockable rhythms, respectively. Of these patients, 1033 (75.7%) with shockable and 7844 (80.6%) with nonshockable rhythms, respectively, were assigned to the AAM preferred group. Favorable neurological outcomes were significantly more frequent in the AAM preferred group than in the IVAd preferred group in patients with a shockable rhythm (13.6% vs 9.3%, respectively; P = 0.039), but not in those with a nonshockable rhythm (1.0% vs 0.8%, respectively; P = 0.509). Preferred AAM was independently associated with a higher probability of favorable neurological outcomes in patients with a shockable rhythm (adjusted odds ratio 1.66, 95% confidence interval 1.08-2.53, P = 0.020), but not in patients with a nonshockable rhythm. CONCLUSIONS: AAM provided by EMS in preference to IVAd was associated with the favorable neurological outcomes of OHCA patients with shockable rhythms.

Anaphylactic Shock After Intramuscular Diclofenac Sodium: A Case Report.

Diclofenac sodium is a commonly used nonsteroidal anti-inflammatory drug. It is widely used for acute and chronic pain management. Side effects, such as fixed drug eruption, asthmatic attack, and vasospastic angina, are commonly seen after the use of diclofenac sodium. However, anaphylaxis and anaphylactic shock secondary to injection of diclofenac sodium are rare. Our main aim in reporting this adverse event is to alert healthcare professionals to this potentially life-threatening adverse effect of diclofenac sodium and prompt use of adrenaline for treatment.

THE PECULIARITIES OF BIOCHEMICAL AND MORPHOLOGICAL CHANGES IN THE HEART OF THE CASTRATED RATS IN THE DEVELOPMENT OF ADRENALIN DAMAGE OF HEART.

OBJECTIVE: The aim of the study was to evaluate the state of oxidation processes and morphological changes in the heart of castrated rats during the development of epinephrine heart damage (EHD). PATIENTS AND METHODS: Materials and methods. The study was performed on 120 white male Wistar rats. The animals were divided into four series: 1 - control, 2 - castration. For EHD, rats were injected once intraperitoneally with a 0.18% solution of adrenaline hydrotartrate at the rate of 0.5 mg/kg of weight. Castration was performed under anesthesia. The concentration of diene and triene conjugates (DC, TC), Schiff's bases (SB), TBA-active products (TBA-ap), oxidatively modi"ed proteins (OMP), activity of superoxide dismutase (SOD) and catalase (CAT) were determined in the heart. A morphological study of preparations stained with Azantrichrome was carried out. All studies were performed in control, 1, 3, 7, 14 and 28 days after adrenaline injection. RESULTS: Results: In the I series DC and TC increased after 1 day of EHD, fell to control values after 3 days, and then had wave-like character (highest - after 14 days). SB decreased (minimal after 7 days), TBA-ap increase (maximal after 14 days). OMP370 increased after 1 and 3 days, after 7 days they did not differ from the control, after 14 days they were higher than in control, and after 28 days they decreased to the control values. OMP430 and OMP530were greater than the control indicators in all terms, except the last; the maximum was noted after 14 days. The activity of antioxidant enzymes was lower than the control indicators at all times of the study. Castration caused an increase of lipid peroxidation. After 7 days, DC and TC, were lower and SB - higher, than in the I series. Castration caused a decrease in OMP. In EHD all values of OMP, compared to the castrated control rats, were higher at all studed times Castration leads to increase of SOD, and decrase of CAT. All indicators of SOD and CAT exceeded the indicators of animals of the I series at all times of the study. Biochemical changes are consistent with morphological changes. After injection of epinephrine, severe vascular disorders, adventitia edema, perivasal edema, endothelial cell damage, dilatation of hemicapillaries, full blood vessels, stasis, hemorrhages in the surrounding tissues, and sclerosing of the walls of arteries and venules were observed. Cardiomyocytes were swollen, shortening, necrosis was observed, myocytolysis was noted. Edema of the stroma was noted. In the stroma, around the vessels, located cells of connective tissue elements were observed. Indicate more damage to the myocardium in the process of development of EHD in animals of the I series. CONCLUSION: Conclusions: Castration of rats causes an increase of lipid peroxidation products and CAT activity in the heart, but a decrease in the content of OMP. Adrenaline injection causes activation of lipid peroxidation and an increase in the content of OMP. During the development of EHD, the activity of antioxidants is significantly higher in II group. Biochemical changes are consistent with morphological, and indicate more damage to the myocardium in the development of EHD in animals of the I series.

In-hospital cardiac arrest: Incidence, prognostic factors and results.

BACKGROUND AND AIMS: In-hospital cardiac arrest (CA) is a clinical entity with high morbidity and mortality that occurs in up to 2% of hospitalized patients. It is a public health problem with important economic, social, and medical repercussions, and as such its incidence needs to be reviewed and improved. The aim of this study was to determine the incidence of in-hospital CA, return of spontaneous circulation (ROSC), and survival rates at Hospital de la Princesa, and to define the clinical and demographic characteristics of patients with in-hospital CA. PATIENTS AND METHODS: Retrospective observational chart review of patients presenting in-hospital CA and treated by anaesthesiologists from the hospital's rapid intervention team. Data were collected over 1 year. RESULTS: Forty four patients were included in the study, of which 22 (50%) were women. Mean age was 75.7 years (±15.78 years), and incidence of in-hospital CA was 2.88 per 100,000 hospital admissions. Twenty two patients (50%) achieved ROSC and 11 patients (25%) survived until discharge home. The most prevalent comorbidity was arterial hypertension (63.64%); 66.7% of cases were not witnessed, and only 15.9% presented a shockable rhythm. CONCLUSIONS: These results are similar to those reported in other larger studies. We recommend introducing immediate intervention teams and devoting time to training hospital staff in in-hospital CA.

Virtual Reality Based Active Shooter Training Drill Increases Salivary and Subjective Markers of Stress.

Law enforcement personnel are required to respond to a variety of dangerous, potentially life-threatening high stress scenarios. Virtual reality (VR)-based training has been shown to attenuate stress responses; however, little is known about the acute stress response from VR exposure. This study examined the impact of participating in a VR-based active shooter training drill (ASD) on markers of physiological stress as well as potential differences in men and women. To examine the impact of participation in a ~50 sec VR-based ASD, 29 subjects (n = 29; 17 males, 12 females) participated in a quasi-experimental single group design. Saliva samples were collected and analyzed from 27 of the 29 subjects a total of four times 1) 30-min prior to, 2) 5-min prior to, 3) 5-min after, and 4) 30-min after the ASD and analyzed for α-amylase (AA) activity and concentrations of secretory immunoglobulin-A (SIgA), cortisol (CORT), and uric acid (UA). Participation in the ASD resulted in a significant (p < 0.05) increase in salivary stress markers AA and SIgA. In addition, lower concentrations of CORT and UA were found in women compared to men. These findings have implications for law enforcement and/or military personnel that may seek to implement a VR-based training into their training regimen. Future studies should investigate the impact of longitudinal participation in ASD interventions to determine if this is an effective training method to reduce stress responses to real life active shooter training drills.

Nuclear organization of catecholaminergic neurons in the brains of a lar gibbon and a chimpanzee.

Using tyrosine hydroxylase immunohistochemistry, we describe the nuclear parcellation of the catecholaminergic system in the brains of a lar gibbon (Hylobates lar) and a chimpanzee (Pan troglodytes). The parcellation of catecholaminergic nuclei in the brains of both apes is virtually identical to that observed in humans and shows very strong similarities to that observed in mammals more generally, particularly other primates. Specific variations of this system in the apes studied include an unusual high-density cluster of A10dc neurons, an enlarged retrorubral nucleus (A8), and an expanded distribution of the neurons forming the dorsolateral division of the locus coeruleus (A4). The additional A10dc neurons may improve dopaminergic modulation of the extended amygdala, the enlarged A8 nucleus may be related to the increased use of communicative facial expressions in the hominoids compared to other primates, while the expansion of the A4 nucleus appears to be related to accelerated evolution of the cerebellum in the hominoids compared to other primates. In addition, we report the presence of a compact division of the locus coeruleus proper (A6c), as seen in other primates, that is not present in other mammals apart from megachiropteran bats. The presence of this nucleus in primates and megachiropteran bats may reflect homology or homoplasy, depending on the evolutionary scenario adopted. The fact that the complement of homologous catecholaminergic nuclei is mostly consistent across mammals, including primates, is advantageous for the selection of model animals for the study of specific dysfunctions of the catecholaminergic system in humans.

Research of spontaneous and stimulated functional activity of platelets in patients with different types of atrial fibrillation.

Platelet function testing is widely used to diagnose disorders of the cellular link of hemostasis. The study of platelet aggregation activity is relevant for the prevention of thromboembolic complications in atrial fibrillation and monitoring the effectiveness and safety of therapy. In this study, a comparative analysis of spontaneous and stimulated platelet aggregation in groups of patients with two types of atrial fibrillation was performed - paroxysmal and persistent. The effect of ß-adrenoblocker therapy on platelet aggregation activity in patients with atrial fibrillation was also studied. Platelet aggregation activity was studied using the method of G. Born in the modification of Z.A. Gabbasov on a two-channel laser analyzer "Biola". Collagen at a concentration of 2 mg / ml and adrenaline in a concentration range of 2.5-10 µg / ml were used as aggregation-promoting agents. It has been established that spontaneous aggregation potential and collagen-induced platelet aggregation depend on the type of atrial fibrillation, as well as on the presence or absence of ß-blockers in therapy. The response of platelets to stimulation with adrenaline depends, first of all, on the type of atrial fibrillation and the concentration of adrenaline in the reaction medium. The most significant changes were noted in the group of patients with a paroxysmal form atrial fibrillation, taking ß-blockers in therapy.

Intraoperative Pain Sensation During Cataract Surgery: Why Does Timing Matter?

Purpose: To investigate whether timing influences pain perception during cataract surgery and to investigate the possible mechanisms.Methods: Patients scheduled for cataract surgery both in the morning and afternoon were consecutively enrolled. Questionnaires to evaluate anxiety, including the Simplified State-Trait Anxiety Inventory, Amsterdam Preoperative Anxiety and Information Scale, and a visual analogue scale (VAS) for anxiety, were completed preoperatively, whereas a VAS for pain and the Wong-Baker FACES® Pain Rating Scale questionnaire were completed after surgery. Preoperative blood pressure and heart rate were recorded. Blood samples were acquired before surgery, and plasma cortisol, adrenocorticotropic hormone, adrenalin, and noradrenalin were tested.Results: Fifty-five patients underwent uneverntful cataract surgery (28 in the morning and 27 in the afternoon) were included in the final analysis. Greater intraoperative pain perception during cataract surgery was reported in the afternoon than in the morning. Overall anxiety levels were significantly higher in the afternoon. Plasma adrenalin levels were significantly higher in the afternoon. Cortisol levels were higher in the afternoon. Preoperative anxiety levels were closely related to intraoperative pain perception. Both adrenalin and cortisol correlated positively with preoperative anxiety, but only adrenalin correlated significantly with the pain scores.Conclusions: Patients undergoing cataract surgery in the afternoon showed more preoperative anxiety, which may have increased their relevant stress hormones. Both the patient's emotional state and hormone levels may together aggravate his/her perceived pain in the afternoon. Monitoring preoperative anxiety levels, blood pressure, and heart rate should help to identify patients at higher risk of perceived intraoperative pain.Clinical trial registration:Trial registration number: NCT02182921Registration site: clinicaltrials.gov.

Arrhythmogenic Interaction Between Sympathetic Tone and Mechanical Stretch in Rat Pulmonary Vein Myocardium.

Rapid firing from pulmonary veins (PVs) frequently initiates atrial fibrillation, which is a common comorbidity associated with hypertension, heart failure, and valvular disease, i.e., conditions that pathologically increase cardiomyocyte stretch. Autonomic tone plays a crucial role in PV arrhythmogenesis, while its interplay with myocardium stretch remains uncertain. Two-microelectrode technique was used to characterize electrophysiological response of Wistar rat PV to adrenaline at baseline and under mild (150 mg of applied weight that corresponds to a pulmonary venous pressure of 1 mmHg) and moderate (10 g, ∼26 mmHg) stretch. Low concentrations of adrenaline (25-100 nmol/L) depolarized the resting membrane potential selectively within distal PV (by 26 ± 2 mV at baseline, by 18 ± 1 mV at 150 mg, P < 0.001, and by 5.9 ± 1.1 mV at 10 g, P < 0.01) suppressing action potential amplitude and resulting in intra-PV conduction dissociation and rare episodes of spontaneous activity (arrhythmia index of 0.4 ± 0.2, NS vs. no activity at baseline). In contrast, 1-10 µmol/L of adrenaline recovered intra-PV propagation. While mild stretch did not affect PV electrophysiology at baseline, moderate stretch depolarized the resting potential within distal PV (-56 ± 2 mV vs. -82 ± 1 mV at baseline, P < 0.01), facilitated the triggering of rapid PV firing by adrenaline (arrhythmia index: 4.4 ± 0.2 vs. 1.3 ± 0.4 in unstretched, P < 0.001, and 1.7 ± 0.8 in mildly stretched preparations, P < 0.005, at 10 µmol/L adrenaline) and induced frequent episodes of potentially arrhythmogenic atrial "echo" extra beats. Our findings demonstrate complex interactions between the sympathetic tone and mechanical stretch in the development of arrhythmogenic activity within PVs that may impact an increased atrial fibrillation vulnerability in patients with elevated blood pressure.

The adrenergic-induced ERK3 pathway drives lipolysis and suppresses energy dissipation.

Obesity-induced diabetes affects >400 million people worldwide. Uncontrolled lipolysis (free fatty acid release from adipocytes) can contribute to diabetes and obesity. To identify future therapeutic avenues targeting this pathway, we performed a high-throughput screen and identified the extracellular-regulated kinase 3 (ERK3) as a hit. We demonstrated that ß-adrenergic stimulation stabilizes ERK3, leading to the formation of a complex with the cofactor MAP kinase-activated protein kinase 5 (MK5), thereby driving lipolysis. Mechanistically, we identified a downstream target of the ERK3/MK5 pathway, the transcription factor FOXO1, which promotes the expression of the major lipolytic enzyme ATGL. Finally, we provide evidence that targeted deletion of ERK3 in mouse adipocytes inhibits lipolysis, but elevates energy dissipation, promoting lean phenotype and ameliorating diabetes. Thus, ERK3/MK5 represents a previously unrecognized signaling axis in adipose tissue and an attractive target for future therapies aiming to combat obesity-induced diabetes.

[Clinical Practice Guide for Anaphylaxis in Latin America (Galaxia-Latam)]. / Guía de Actuación en Anafilaxia en Latinoamérica. Galaxia-Latam.

Anaphylaxis is a severe allergic reaction with a rapid onset and it is potentially life-threatening. Its clinical manifestations are varied; they may affect the skin, the cardiovascular system, the respiratory system, and the digestive system, among others. The treatment of choice, which is an intra-muscular injection of epinephrine (adrenaline), must be applied promptly. Therefore, being prepared to recognize it properly is of crucial importance. The objective of this clinical practice guide is to improve the knowledge of health professionals about anaphylaxis and, consequently, to optimize the treatment and long-term management of this reaction. This guide is adapted to the peculiarities of Latin America; especially in matters regarding the treatment. The need to introduce epinephrine auto-injectors in countries that don't have them yet is highlighted.

La anafilaxia es una reacción alérgica grave de instauración rápida y potencialmente mortal. Sus manifestaciones clínicas son muy variadas, pudiendo afectar la piel, el sistema cardiovascular, el aparato respiratorio y el digestivo, entre otros. El tratamiento de elección, mediante la inyección intramuscular de adrenalina, debe ser precoz. Por lo anterior, es vital estar preparados para reconocerla adecuadamente. El objetivo de la presente guía de actuación clínica es mejorar el conocimiento de los profesionales sanitarios sobre anafilaxia y, consecuentemente, optimizar el tratamiento y manejo a largo plazo de esta entidad. La guía está adaptada a las peculiaridades de América Latina, especialmente en los aspectos relativos al tratamiento. Se destaca la necesidad de introducir los autoinyectores de adrenalina en los países que no dispongan de ellos.

Greater palatine canal injections reduce operative bleeding during endoscopic sinus surgery: a systematic review and meta-analysis.

OBJECTIVES: The use of greater palatine canal (GPC) injections of a local anesthetic and a vasoconstrictor to decrease surgical bleeding during endoscopic sinus surgery (ESS) is controversial. We investigated the role of a preoperative GPC injection to minimize intraoperative bleeding during ESS in patients with chronic sinusitis through a meta-analysis of the relevant literature. DATA SOURCES: PubMed, SCOPUS, and the Cochrane database. REVIEW METHODS: We screened the relevant literature published before May of 2018. Five articles that compared the pre-operative GPC injection (treatment group) with a placebo or no treatment (control group) were included for this analysis of the outcomes, which included an endoscopic grade of nasal bleeding and intraoperative hemodynamic stability during ESS. RESULTS: The endoscopic grade in the treatment group was significantly reduced when compared with the control group. No significant adverse effects were reported in the enrolled studies. The subgroup analyses of these results compared the concentrations of adrenalin (1:80,000 or 1:100,000), and adrenalin 1:80,000 showed significant effects on intraoperative bleeding when compared to adrenalin 1:100,000. CONCLUSION: This study demonstrated that GPC injections of local anesthesia with 1:80,000 adrenaline for ESS effectively reduced intraoperative bleeding. Additionally, this procedure showed no significant adverse effects, such as hemodynamic instability. However, the standardized dosing needs further investigation and more trials. LEVEL OF EVIDENCE: Ia.

Mechanism of Huanglian Ejiao Tang on Prevention and Treatment of Myocardial Injury Induced by Anthracycline Chemotherapy Drugs / 中国实验方剂学杂志

Objective: To observe the preventive and therapeutic effect of Huanglian Ejiao Tang on myocardial injury induced by anthracycline chemotherapeutic drugs in all kinds of cancer patients undergoing chemotherapy. Method:We chosen all kinds of cancer patients with combined use of anthracycline chemotherapy drugs in our hospital, 21 days as one cycle. The cardiac toxicity reaction was observed after three continuous chemotherapy cycles. A total of 64 patients who met the dialectical criteria of "imbalance between heart-Yang and kidney-Yin" were randomly divided into treatment group (32 cases) and control group (32 cases). Patients in treatment group were treated with Chinese medicine Huanglian Ejiao Tang based on original chemotherapy regimen, adding and subtracting Chinese medical materials according to the symptoms. Patients in control group continued to maintain the original chemotherapy regimen, and both two groups of patients continued to receive 3 cycles of continuous chemotherapy. By comparing the cardiac function classification and cardiac function tolerance between the 3 cycles and 6 cycles of two groups of patients after chemotherapy; changes of echocardiography index, QTc interval, creatine kinase isoenzyme (CK-MB), Myoglobin (MYO), cardiac troponin I (cTNI)and nitrogenous terminal-pro-brain natriuretic peptide(NT-pro-BNP) concentration value were compared between two groups; and the concentrations of adrenaline (E), norepinephrine (NE) and angiotensin Ⅱ(AngⅡ) were observed and compared; meanwhile, the correlation analysis was carried out at the same time. Result:After 6 cycles of chemotherapy in Chinese medicine treatment group, degree of cardiac function classification and the 6 minute walking heart function tolerance were significantly better than those at the 3 cycles of chemotherapy (PPPPPConclusion:Huanglian Ejiao Tang can reduce the excitability of the symppthetic nervous system (SNS) and renin-angiotensin system(RAS) in human body and inhibit the release level of NE, E and AngⅡ by effect of "invigorating the kidney and clearing the heart". It has a certain preventive and treatment effect on the cardiac toxicity of patients with the cumulative use of anthracycline chemotherapy. To a certain extent, it can inhibit myocardial injury, improve cardiac function and reduce the incidence of cardiovascular events.

[Determination of 5-hydroxytryptamine,Adrenalin and Noradrenalin in Human Plasma by Pre-column Derivatization HPLC-MS/MS].

OBJECTIVE: To establish a method for the determination of 5-hydroxy tryptamine (5-HT),adrenalin (AD) and noradrenalin (NA) in human plasma using pre-column derivatization HPLC-MS/MS. Methods Derivatives of the plasma samples were produced with dansyl chloride under pH 10.5,and then extracted and enriched with ethyl acetate. The detected chemicals were separated using Ultimate C18 (50 mm×4.6 mm,5 µm) with acetonitrile-water-formic acid=95∶5∶0.05 (V∶V∶V) at 0.2 mL/min. The HPLC-MS//MS system was operated under a multiple reaction monitoring mode (MRM) using the electrospray ionization technique in positive mode. RESULTS: Linear range of the calibration curve appeared in 250-2.5 ng/mL. The method had a less than 9% intra- and inter-assay relative standard deviation (RSD),95.44%-109.71% recoveries,and 4.86%-12.81% matrix effects. CONCLUSION: This method is simple,accurate,and suitable for detection of 5-HT,AD and NA in human plasma.

Real-life comparison of three general paediatric wards showed similar outcomes for children with bronchiolitis despite different treatment regimens.

AIM: This study evaluated the effectiveness of three different treatments for bronchiolitis in a tertiary paediatric facility. METHODS: Patients with bronchiolitis who were younger than two years of age and were randomly allocated to three general wards at Schneider Children's Medical Center, Israel, after admission were included. Different treatment protocols in the wards were retrospectively compared. RESULTS: The study comprised 286 children. The clinical and laboratory parameters on admission were similar between the wards. In Ward C where nebulised hypertonic saline was infrequently administered (6.7%), the mean number of days with oxygen saturation under 92% and the meanlength of hospital stay (1.8 and 3.8 days) were significantly lower than Ward A (2.8 and 5.3 days) and Ward B, (2.9 and 4.7 days) where nebulised hypertonic saline was given more frequently (38.7%-74.7%). Multivariate analysis indicated that low saturation on admission, leukocytosis and use of nebulised hypertonic saline or adrenalin were independent predictors of a longer period of desaturation and hospital stay. CONCLUSION: Different treatment protocols for bronchiolitis were used in three paediatric wards in this real-life study. No treatment regimen proved superior. Inhalations of hypertonic saline or adrenaline were associated with a longer hospital stay.

Changes in cardiovascular function based on adrenalin and norepinephrine metabolism in ovariectomized rats.

Menopause is a cardiovascular risk factor in women, and cardiovascular changes during perimenopause can increase the risk. We observed the influence of plasma adrenalin and norepinephrine and their metabolites on the cardiovascular system and the rectification effect of estrogen in ovariectomized rats. Fifty-four adult female Sprague-Dawley rats were randomly divided into sham (Sham), ovariectomized (OVX), or ovariectomized+estrogen treatment groups (OVX+E), with 18 rats in each. The Sham and OVX groups were given normal saline and the OVX+E group was given estradiol valerate beginning 2weeks after ovariectomy and continuing for 4weeks. Radioimmunoassay, high-performance liquid chromatography, high-performance liquid chromatography-tandem mass spectrometry, and chromatography-spectrophotometry were used to detect estradiol, adrenalin, norepinephrine, metanephrine, and normetanephrine in plasma and vanillylmandelic acid in urine. Echocardiography, Doppler blood flow detection technologyand hamnatodynamometer were applied to assess cardiovascular function. After ovariectomy, levels of estrogen reduced, adrenalin and metanephrine increased, and norepinephrine and normetanephrine in the plasma and vanillylmandelic acid in urine decreased. Symptoms indicative of cardiac diastolic dysfunction, including decreased diastolic left ventricular cavity capacity, increased wall thickness and decreased cardiac rate were observed. Different degrees of vasomotor dysfunction appeared in different peripheral positions, and the tail vessels were in relatively systolic conditions. However, the claw pad vessels were diastolic. Besides, blood pressure also increased. After ovariectomy, estrogen levels reduced and the metabolic processes of adrenalin and norepinephrine changed, which impacted cardiovascular functions. Changes of adrenalin and norepinephrine and its metabolites were correlated with the cardiovascular function. Cardiovascular disease occurred during the perimenopausal period. Estrogen replacement therapy can mitigate, rectify, and improve menopause-related conditions such as hot flash.

Identifying binding modes of two synthetic derivatives of adrenalin to the α2C-adrenoceptor by using molecular modeling; insights into the α2C-adrenoceptor activation.

Although, α2C adrenergic receptor (AR) mediates a number of physiological functions in vivo and has great therapeutic potential, the absence of its crystal structure is a major difficulty in the activation mechanism studies and drug design endeavors. Here, a homology model of α2C AR has been presented by means of multiple sequence alignment. The used templates were the latest crystal structures of the other ARs (Protein Data Bank IDs: 2R4R, 2RH1, 4GPO, 3P0G, 4BVN and 4LDO) that have 38.4% identity with the query. We then conducted docking simulations to understand and analyze the binding of noradrenaline (NOR), and its derivatives, namely arachidonoyl adrenalin (AA-AD) and arachidonoyl noradrenalin (AA-NOR) to the receptor. The existence of H-bonds between the ligands and SER218 residue implies the same binding site of derivatives with respect to the NOR. AA-AD and AA-NOR bind to the receptor with the larger binding affinities. The presence of salt bridge between ARG149 and GLU377 in the free receptor, obtained from molecular dynamics studies proved that the receptor still is in its basal state before binding process take places. The activation process is characterized by increasing in the RMSD values of the backbone receptor in the bound state, increasing the RMSF of the transmembrane involved in the activation process and the disappearance of the ARG149-GLU377 salt bridge.

The impact of theaflavins on systemic-and microcirculation alterations: The murine and randomized feasibility trials.

Theaflavins are polyphenols found in black tea; their physiological activities were not well investigated. The present study in rats evaluated the influence of theaflavins on circulation. In addition, an intervention pilot study examined the influence of a theaflavin drink on postprandial hemodynamic change. In an animal study, a single oral dose of theaflavin rich fraction (TF, 10mg/kg) caused transient increase in mean blood pressure (MBP) and heart rate (HR). TF also elevated cremastric blood flow significantly, and the magnitude of this effect was in this order: theaflavin 3'-O-gallate (TF2B) >>theaflavin-3-O-gallate (TF2A) >>theaflavin (TF1)=theaflavin-3, 3'-di-O-gallate (TF3). In addition, these hemodynamic alterations in mammals totally disappeared when pretreated with carvedilol as an adrenaline blocker. We also treated 10-mg/kg/day TF to the rats for 2 weeks. At the end of the ingestion period, MBP was reduced significantly, and aortic eNOS level was elevated by the repeated ingestion of TF compared with distilled water. In the intervention trial, blood pressure of the volunteers was increased significantly 2 and 4h after ingestion of the TF drink (45mg/drink) compared with before treatment. A significant difference was observed in FMD between the placebo and theaflavin groups 4h after ingestion. These results suggested that theaflavin has potent activity to alter hemodynamics in both murine and healthy subjects. Further studies is needed to elucidate the details; however, the results of animal study suggested that the possible involvement of sympathetic nervous system in the hemodynamic changes caused by TF.