Hypoglycemia induces vascular endothelial dysfunction in subjects with normal glucose tolerance.

This prospective study determined the effects of hypoglycemic stimulation on vascular endothelial function in non-diabetic patients using reactive hyperemia peripheral arterial tonometry (RH-PAT). The study included non-diabetic patients who were hospitalized for an insulin tolerance test (ITT) for the diagnosis of hypoadrenocorticism or hypopituitarism. Vascular endothelial function was assessed using the reactive hyperemia index (RHI) measured by the RH-PAT. We also measured the levels of anterior pituitary hormone, adrenaline, noradrenaline, and dopamine at the time of hypoglycemia. The primary endpoint was a change in the RHI at 120 min after insulin administration. The study included 27 patients. ITT was associated with significant increases in systolic blood pressure, pulse rate, and the blood levels of adrenocorticotropic hormone, cortisol, growth hormone, adrenaline, noradrenaline, and dopamine. RHI significantly decreased after ITT from 2.24 ± 0.51 to 1.71 ± 0.42. A significant inverse correlation was observed between the change in RHI and change in adrenaline (r = - 0.670, p = 0.012). We concluded that hypoglycemic stimulation altered vascular endothelial function, as measured by RH-PAT, even in patients free of glucose intolerance. The observed deterioration in vascular endothelial function correlated with increases in catecholamine levels during hypoglycemia.Trial registration: UMIN000033244.

Associations of neurotransmitters and the gut microbiome with emotional distress in mixed type of irritable bowel syndrome.

Evidence highlights the comorbidity between emotional distress and irritable bowel syndrome (IBS) through the gut-brain axis. However, the underlying mechanism is largely unknown. Thus, the present study aimed to evaluate the associations among neurotransmitter levels and the gut microbiome profiles in persons with IBS and emotional distress. In this nested case-controlled study, emotional symptoms, including anxiety and depressive symptoms, were evaluated in 40 persons with IBS and 20 healthy controls (HC). Plasma neurotransmitters levels (serotonin and norepinephrine) and the gut microbiome profile of the collected fecal samples were examined. Emotional distress and microbiome profile were significantly different between IBS and HC groups. Lower but not significant neurotransmitters' levels (serotonin and norepinephrine) were observed in the IBS group compared to the HC. A negative correlation was found between norepinephrine levels and alpha diversity (Shannon and Simpson indices) in the IBS group. Moreover, serotonin levels were positively associated with the abundance of Proteobacteria, and norepinephrine were positively correlated with Bacteroidetes, but negatively associated with Firmicutes phylum. The present study demonstrated alteration in the gut microbiome between persons with IBS and emotional distress compared to HC. The correlations between plasma neurotransmitters and the gut microbiome suggest that the gut microbiome may impact the regulation of neurotransmitters.

Sympathetic neural responses to sleep disorders and insufficiencies.

Short sleep duration and poor sleep quality are associated with cardiovascular risk, and sympathetic nervous system (SNS) dysfunction appears to be a key contributor. The present review will characterize sympathetic function across several sleep disorders and insufficiencies in humans, including sleep deprivation, insomnia, narcolepsy, and obstructive sleep apnea (OSA). We will focus on direct assessments of sympathetic activation, e.g., plasma norepinephrine and muscle sympathetic nerve activity, but include heart rate variability (HRV) when direct assessments are lacking. The review also highlights sex as a key biological variable. Experimental models of total sleep deprivation and sleep restriction are converging to support several epidemiological studies reporting an association between short sleep duration and hypertension, especially in women. A systemic increase of SNS activity via plasma norepinephrine is present with insomnia and has also been confirmed with direct, regionally specific evidence from microneurographic studies. Narcolepsy is characterized by autonomic dysfunction via both HRV and microneurographic studies but with opposing conclusions regarding SNS activation. Robust sympathoexcitation is well documented in OSA and is related to baroreflex and chemoreflex dysfunction. Treatment of OSA with continuous positive airway pressure results in sympathoinhibition. In summary, sleep disorders and insufficiencies are often characterized by sympathoexcitation and/or sympathetic/baroreflex dysfunction, with several studies suggesting women may be at heightened risk.

The Dual Role of the ß2-Adrenoreceptor in the Modulation of IL-17 and IFN-γ Production by T Cells in Multiple Sclerosis.

Norepinephrine is a neurotransmitter that also has an immunomodulatory effect and is involved in multiple sclerosis (MS) pathogenesis. This study aimed to clarify the role of the ß2-adrenoreceptor in the norepinephrine-mediated modulation of interleukin-17 (IL-17) and interferon-γ (IFN-γ) production, which play a critical pathogenetic role in MS. CD4+ T cells obtained from twenty-five relapsing-remitting MS patients and sixteen healthy subjects were cultured ex vivo with norepinephrine and/or ß2-adrenoreceptor antagonist or agonist, followed by a cytokine production analysis using ELISA. Norepinephrine suppressed IL-17 and IFN-γ production by the anti-CD3/anti-CD28-microbead-stimulated CD4+ T cells in both groups. Blockade of the ß2-adrenoreceptor with the specific antagonist ICI 118.551 enhanced norepinephrine-mediated IL-17 suppression but decreased its inhibitory effect on IFN-γ production in MS patients. In contrast, the ß2-adrenoreceptor agonist formoterol did not influence norepinephrine's inhibitory effect on cytokine production in both groups. The blockade of the ß2-adrenoreceptor, even in the absence of exogenous norepinephrine, suppressed IL-17 production but did not influence IFN-γ production in both groups. Conversely, ß2-adrenoreceptor activation by formoterol decreased IFN-γ production and did not affect IL-17 production in both groups. These data illustrate the inhibitory effect of norepinephrine on IL-17 and IFN-γ production by CD4+ T cells in MS. The inhibitory effect of norepinephrine on IFN-γ production by CD4+ T cells in MS could be mediated via ß2-adrenoreceptor activation.

Standardized Autonomic Testing in Patients With Probable Radiation-Induced Afferent Baroreflex Failure.

Injury of the afferent limb of the baroreflex from neck radiation causes radiation-induced afferent baroreflex failure (R-ABF). Identification and management of R-ABF is challenging. We aimed to investigate the pattern of autonomic dysfunction on standardized autonomic testing in patients with probable R-ABF. We retrospectively analyzed all autonomic reflex screens performed at Mayo Clinic in Rochester, MN, between 2000 and 2020 in patients with probable R-ABF. Additional tests reviewed included ambulatory blood pressure monitoring, plasma norepinephrine, and thermoregulatory sweat test. We identified 90 patients with probable R-ABF. Median total composite autonomic severity score (range, 0-10) was 7 (interquartile range, 6-7). Cardiovascular adrenergic impairment was seen in 85 patients (94.4%), increased blood pressure recovery time after Valsalva maneuver in 71 patients (78.9%; median 17.4 seconds), and orthostatic hypotension in 68 patients (75.6%). Cardiovagal impairment was demonstrated by abnormal heart rate responses to deep breathing (79.5%), Valsalva ratio (87.2%), and vagal baroreflex sensitivity (57.9%). Plasma norepinephrine was elevated and rose appropriately upon standing (722-1207 pg/mL). Ambulatory blood pressure monitoring revealed hypertension, postural hypotension, hypertensive surges, tachycardia, and absence of nocturnal dipping. Blood pressure lability correlated with impaired vagal baroreflex function. Postganglionic sympathetic sudomotor function was normal in most cases; the most frequent thermoregulatory sweat test finding was focal neck anhidrosis (78.9%). Standardized autonomic testing in R-ABF demonstrates cardiovascular adrenergic impairment with orthostatic hypotension, blood pressure lability, and elevated plasma norepinephrine. Cardiovagal impairment is common, while sudomotor deficits are limited to direct radiation effects.

Distinct expression and clinical value of aquaporin 4 in children with hand, foot and mouth disease caused by enterovirus 71.

Brain dysfunction is a prerequisite for critical complications in children with hand, foot, and mouth disease (HFMD). Aquaporin 4 (AQP-4) may be involved in the pathological process of cerebral oedema and injury in children with severe and critical HFMD. This study aimed to assess the association of AQP-4 with the severity of enterovirus 71 (EV71)-associated HFMD. Children with EV71-infected HFMD were divided into a common group (clinical stage 1), a severe group (clinical stage 2), and a critical group (clinical stage 3) according to Chinese guidelines. The levels of AQP-4, interleukin-6 (IL-6), norepinephrine (NE), and neuron-specific enolase (NSE) before and after treatment were tested. Serum AQP-4, IL-6, NE, and NSE levels showed significant differences among the critical, severe, and common groups before and after treatment (P < 0.01). No significant differences in AQP-4 levels in cerebrospinal fluid (CSF) were observed between the critical and severe groups before and after treatment, but the CSF AQP-4 levels in these two groups were higher than those in the common group before treatment (P < 0.01). Serum AQP-4 levels, but not CSF AQP-4 levels, closely correlated with serum IL-6, NE, and NSE levels. These results suggest that the level of AQP-4 in serum, but not in CSF, is a candidate biomarker for evaluating the severity and prognosis of EV71-associated HFMD.

Effect of a high-fat diet and chromium on hormones level and Cr retention in rats.

AIMS: The aim of the study was to determine how the administration of a high-fat diet supplemented with various forms of chromium to rats affects accumulation of this element in the tissues and levels of leptin, ghrelin, insulin, glucagon, serotonin, noradrenaline and histamine, as well as selected mineral elements. METHODS: The experiment was conducted on 56 male Wistar rats, which were divided into 8 experimental groups. The rats received standard diet or high fat diet (HFD) with addition of 0.3 mg/kg body weight of chromium(III) picolinate (Cr-Pic), chromium(III)-methioninate (Cr-Met), or chromium nanoparticles (Cr-NP). RESULTS: Chromium in organic forms was found to be better retained in the body of rats than Cr in nanoparticles form. However, Cr-Pic was the only form that increased the insulin level, which indicates its beneficial effect on carbohydrate metabolism. In blood plasma of rats fed a high-fat diet noted an increased level of serotonin and a reduced level of noradrenaline. The addition of Cr to the diet, irrespective of its form, also increased the serotonin level, which should be considered a beneficial effect. Rats fed a high-fat diet had an unfavourable reduction in the plasma concentrations of Ca, P, Mg and Zn. The reduction of P in the plasma induced by supplementation with Cr in the form of Cr-Pic or Cr-NP may exacerbate the adverse effect of a high-fat diet on the level of this element. CONCLUSION: A high-fat diet was shown to negatively affect the level of hormones regulating carbohydrate metabolism (increasing leptin levels and decreasing levels of ghrelin and insulin).

Correlation of Antibodies to Neurotransmitters in the Sera of Women with Alcohol Dependence and Depressive Disorders.

Comparative analysis of blood sera from women with alcohol dependence and depressive disorders or from conditionally healthy women revealed reduced level of antibodies to dopamine, norepinephrine, serotonin, glutamate, and GABA in blood serum in women with dysthymic disorder and a depressive episode and their increased content in women with alcohol dependence in combination with depressive disorders.

Study of stability and interference for catecholamines and metanephrines, 3-methoxytyramine: key point of an accurate diagnosis for pheochromocytoma and paraganglioma.

BACKGROUND: Accurate diagnosis of pheochromocytoma and paraganglioma (PPGLs) is highly dependent on the detection of metanephrines and catecholamines. However, the systematic investigation on influencing factors including specimen (plasma or whole blood), anticoagulant, storage conditions, and interference factors need further confirmation. METHODS: Blood with heparin-lithium or EDTA-K2 were collected, stability of epinephrine (EPI), norepinephrine (NE), dopamine (DA), metanephrine (MN), normetanephrine (NMN), 3-methoxytyramine (3-MT) in whole blood and plasma at room temperature and 4 °C for different storage times, stability of plasma MN, NMN and 3-MT at -20 °C and -80 °C were investigated. Plasma with hemoglobin (1 g/L, 2 g/L, 3 g/L, 4 g/L, 6 g/L), TG (<5 mmol/L, 5-8 mmol/L, >8 mmol/L) were prepared. RESULTS: EPI, NE, DA were prone to degrade at room temperature, samples should be centrifuged at 4 °C. EPI and NE were stable in whole blood at 4 °C for 4 h and in plasma for 2 h. For MN, NMN, 3-MT, plasma can be stable at room temperature and 4 °C for at least 6 h, which is better than whole blood; there was no significant difference when stored at -20 °C and -80 °C for 7 days. Heparin-lithium had a slight advantage over EDTA-K2. EPI, NE, DA should not be performed when Hb > 1 g/L or TG > 5 mmol/L. MN, NMN, 3-MT should not be performed when Hb > 2 g/L, whereas TG had no interference. CONCLUSIONS: According to the actual clinical application scenario, this study provided a reliable basis for the accurate diagnosis of PPGLs.

Renal Deafferentation Prevents Progression of Hypertension and Changes to Sympathetic Reflexes in a Rabbit Model of Chronic Kidney Disease.

[Figure: see text].

Liposome-encapsulated hemoglobin (HbV) transfusion rescues rats undergoing progressive lethal 85% hemorrhage as a result of an anti-arrhythmogenic effect on the myocardium.

Liposome-encapsulated hemoglobin vesicles (HbV) can serve as a blood substitute with oxygen-carrying capacity comparable to that of human blood and lethal hemorrhage is associated with lethal arrhythmias. To investigate the resuscitation effect of HbV on lethal hemorrhage and anti-arrhythmogenesis, we performed optical mapping analysis (OMP) and electrophysiological study (EPS) in graded blood exchange (85% blood loss) in the rat model. We also measured cardiac autonomic activity, as assessed by heart rate variability (HRV), and changes in plasma norepinephrine and left ventricle ejection fraction (LVEF) by echocardiography. Pathological study on Connexin43 was performed. A 5% albumin (ALB group), washed rat erythrocytes (wRBC group), and HbV (HbV group) were used as a resuscitation fluid. The survival effects over 24 hours were examined. All rats died in the ALB group, whereas almost all survived for 24-hours period in wRBC and HbV groups. OMP showed impaired action potential duration dispersion (APDd) in the ALB group, whereas normal APDs in HbV and wRBC groups. Lethal arrhythmias were induced by EPS in the ALB group, but not in wRBC and HbV groups. HRV indices, LVEF, Connexin43 were preserved in HbV and wRBC groups. Lethal hemorrhage causes lethal arrhythmias in the presence of impaired APDd. HbV acutely rescues lethal hemorrhage by preventing lethal arrhythmias and preserving arrhythmogenic factors.

Effect of exercise intensity and duration on the levels of stress hormones and hypothalamic-pituitary-gonadal axis in adult male rats: an experimental study.

PURPOSE: The effect of exercise on stress has been demonstrated in several studies which have shown that exercise intensity and duration have various effects on the reproductive axis. This study evaluated the effect of different intensities and durations of exercise on the hormonal indices of stress, such as corticosterone (CORT), norepinephrine (NEP), and also reproductive performance indices, including gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH), and testosterone (T). METHODS: In this experimental study, 30 adult Wistar rats were randomly divided into five groups as follows: no-exercise, RME-1 (regular moderate exercise for 1 month), RME-6 (regular moderate exercise for 6 months), RIE-1 (regular intensive exercise for 1 month), and RIE-6 (regular intensive exercise for 6 months). At the end of the experiment, the serum levels of the abovementioned hormones and hypothalamic expression of the Gnrh gene were measured using the enzyme-linked immunosorbent assay and the real-time polymerase chain reaction method, respectively. RESULTS: The levels of stress hormones, including CORT and NEP, increased only in the RIE-1 group compared with the no-exercise group. In addition, an increase was observed in T hormone levels in the RME-1 group compared with those in the no-exercise group, whereas LH and T hormone levels showed a greater decrease in the RIE-6 group than in the no-exercise group. Gnrh expression levels showed an increase and a decrease in the RME-1 and RIE-6 groups compared with the no-exercise group, respectively. CONCLUSION: These results confirmed the effects of different intensities and durations of exercise on sex hormone levels.

Stability and test-retest reliability of different hormonal stress markers upon exposure to psychosocial stress at a 4-month interval.

The Trier Social Stress Test (TSST) has been shown to reliably induce physiological stress responses in the hypothalamus-pituitary-adrenal (HPA) and in the sympathetic-adrenal-medullary (SAM) axis in cross-sectional studies. However, it was also reported that repeated exposure to the TSST might be associated with habituation, mainly of the HPA axis responsivity. Thus, in all longitudinal stress studies involving repeated TSST administration, potential habituation of the HPA axis response complicates the interpretation of results. The goal of the present study was therefore to assess stability and test-retest reliability of a number of different endocrinological stress markers as well as subjective stress responses after two exposures to the TSST four months apart. We assessed salivary and plasma cortisol profiles, plasma ACTH and noradrenaline profiles, as well as subjective stress ratings in healthy volunteers before, during, and after the TSST at six time-points both at test-day 1 (TSST_1, n = 42) and test-day 2 (TSST_2, n = 34) 4-months later. Half of the participants received the TSST in the early, the other half in the late afternoon. Discontinuous growth models were applied to model three phases of the stress response (preTSST, reactivity, recovery) for each marker. Subsequently, the stability of these phases was analyzed. Stability and test-retest reliability of standard physiological stress markers such as Area-under-the-Curve (AUCG, AUCI), Absolute Peak Change, and Relative Peak Change (RPC) were analyzed as well. We did not observe strong test-retest effects in any of the endocrinological measures. In contrast, test-retest effects in subjective stress were characterized by a faster drop directly after the second TSST, whereas the initial increase before the test period was the same for both test-days. Regarding test-retest-reliability, AUCG was the most reliable measure across all endocrinological and subjective stress markers (range: r = .606 to .858), while AUCI and RPC (range: r = - .146 to .548) were least reliable. A 4-month interval is a sufficient time interval between two repeated TSST exposures to largely reinstate the physiological stress response, which was also true for the initial psychological stress response. Thus, the TSST is well applicable in longitudinal studies.

Modulation of behavioral and neurochemical responses of adult zebrafish by fluoxetine, eicosapentaenoic acid and lipopolysaccharide in the prolonged chronic unpredictable stress model.

Long-term recurrent stress is a common cause of neuropsychiatric disorders. Animal models are widely used to study the pathogenesis of stress-related psychiatric disorders. The zebrafish (Danio rerio) is emerging as a powerful tool to study chronic stress and its mechanisms. Here, we developed a prolonged 11-week chronic unpredictable stress (PCUS) model in zebrafish to more fully mimic chronic stress in human populations. We also examined behavioral and neurochemical alterations in zebrafish, and attempted to modulate these states by 3-week treatment with an antidepressant fluoxetine, a neuroprotective omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA), a pro-inflammatory endotoxin lipopolysaccharide (LPS), and their combinations. Overall, PCUS induced severe anxiety and elevated norepinephrine levels, whereas fluoxetine (alone or combined with other agents) corrected most of these behavioral deficits. While EPA and LPS alone had little effects on the zebrafish PCUS-induced anxiety behavior, both fluoxetine (alone or in combination) and EPA restored norepinephrine levels, whereas LPS + EPA increased dopamine levels. As these data support the validity of PCUS as an effective tool to study stress-related pathologies in zebrafish, further research is needed into the ability of various conventional and novel treatments to modulate behavioral and neurochemical biomarkers of chronic stress in this model organism.

Workplace bullying increases the risk of anxiety through a stress-induced ß2-adrenergic receptor mechanism: a multisource study employing an animal model, cell culture experiments and human data.

OBJECTIVES: Several studies show that severe social stressors, e.g., in the form of exposure to workplace bullying in humans, is associated with negative mental health effects such as depression and anxiety among those targeted. However, the understanding of the underlying biological mechanisms that may explain the relationship between exposure to bullying and such negative health outcomes is scarce. The analyses presented here focus on understanding the role of the ß2-adrenergic receptors (ADRB2) on this association. METHODS: First, a resident-intruder paradigm was used to investigate changes in circulating norepinephrine (NE) in rat serum induced by repeated social defeat and its relationship with subsequent social behavior. Second, the direct effects of the stress-hormones NE and cortisol, i.e., synthetic dexamethasone (DEX), on the ADRB2 expression (qPCR) and monocyte chemoattractant protein-1 (MCP-1) release (immunoassay) was examined in cultured EL-1 cells. Third, in a probability sample of 1052 Norwegian employees, the 9-item short version of the Negative Acts Questionnaire-Revised (S-NAQ) inventory, Hopkins Symptom Checklist and genotyping (SNP TaqMan assay) were used to examine the association between social stress in the form of workplace bullying and anxiety moderated by the ADRB2 genotype (rs1042714) in humans. RESULTS: The present study showed a clear association between reduced social interaction and increased level of circulating NE in rats previously exposed to repeated social defeat. Parallel cell culture work, which was performed to examine the direct effects of NE and DEX on ADRB2, demonstrated ADRB2 downregulation and MCP-1 upregulation in cultured EL-1 cells. Genotyping with regard to the ADRB2 genotype; rs1042714 CC vs CG/GG, on human saliva samples, showed that individuals with CC reported more anxiety following exposure to bullying behaviors as compared to the G carriers. CONCLUSION: We conclude that workplace bullying promotes anxiety and threaten well-being through an ADRB2 associated mechanism.

Comparison of Resveratrol Supplementation and Energy Restriction Effects on Sympathetic Nervous System Activity and Vascular Reactivity: A Randomized Clinical Trial.

Background: Chronic sympathetic nervous system activation is associated with endothelial dysfunction and cardiometabolic disease, which may be modulated by resveratrol (RSV) and energy restriction (ER). This study aimed to examine the effects of RSV and ER on plasma noradrenaline (NA), flow-mediated vasodilation (ed-FMD), and endothelium-independent nitrate-mediated vasodilation (ei-NMD). Methods: The study included 48 healthy adults randomized to 30-days intervention of RSV or ER. Results: Waist circumference, total cholesterol, HDL-c, LDL-c, apoA-I, and plasma NA decreased in the ER group, whilst RSV increased apoB and total cholesterol, without changing plasma NA. No effects on vascular reactivity were observed in both groups. Plasma NA change was positively correlated with total cholesterol (r = 0.443; p = 0.002), triglycerides (r = 0.438; p = 0.002), apoA-I (r = 0.467; p = 0.001), apoB (r = 0.318; p = 0.032) changes, and ei-NMD (OR = 1.294; 95%CI: 1.021-1.640). Conclusions: RSV does not improve cardiometabolic risk factors, sympathetic activity, and endothelial function. ER decreases plasma NA and waist circumference as well as improves blood lipids, but does not modify endothelial function. Finally, plasma NA was associated with ei-NMD, which could be attributed to a higher response to nitrate in patients with greater resting sympathetic vasoconstriction.

Acute hypoglycemia and risk of cardiac arrhythmias in insulin-treated type 2 diabetes and controls.

OBJECTIVE: Hypoglycemia is associated with an increased risk of cardiovascular disease including cardiac arrhythmias. We investigated the effect of hypoglycemia in the setting of acute glycemic fluctuations on cardiac rhythm and cardiac repolarization in insulin-treated patients with type 2 diabetes compared with matched controls without diabetes. DESIGN: A non-randomized, mechanistic intervention study. METHODS: Insulin-treated patients with type 2 diabetes (n = 21, age (mean ± s.d.): 62.8 ± 6.5 years, BMI: 29.0 ± 4.2 kg/m2, HbA1c: 6.8 ± 0.5% (51.0 ± 5.4 mmol/mol)) and matched controls (n = 21, age: 62.2 ± 8.3 years, BMI 29.2 ± 3.5 kg/m2, HbA1c: 5.3 ± 0.3% (34.3 ± 3.3 mmol/mol)) underwent a sequential hyperglycemic and hypoglycemic clamp with three steady-states of plasma glucose: (i) fasting plasma glucose, (ii) hyperglycemia (fasting plasma glucose +10 mmol/L) and (iii) hyperinsulinemic hypoglycemia (plasma glucose < 3.0 mmol/L). Participants underwent continuous ECG monitoring and blood samples for counterregulatory hormones and plasma potassium were obtained. RESULTS: Both groups experienced progressively increasing heart rate corrected QT (Fridericia's formula) interval prolongations during hypoglycemia ((∆mean (95% CI): 31 ms (16, 45) and 39 ms (24, 53) in the group of patients with type 2 diabetes and controls, respectively) with similar increases from baseline at the end of the hypoglycemic phase (P = 0.43). The incidence of ventricular premature beats increased significantly in both groups during hypoglycemia (P = 0.033 and P < 0.0001, respectively). One patient with type 2 diabetes developed atrial fibrillation during recovery from hypoglycemia. CONCLUSIONS: In insulin-treated patients with type 2 diabetes and controls without diabetes, hypoglycemia causes clinically significant and similar increases in cardiac repolarization that might increase vulnerability for serious cardiac arrhythmias and sudden cardiac death.

Predictors of the Pressor Response to the Norepinephrine Transporter Inhibitor, Atomoxetine, in Neurogenic Orthostatic Hypotension.

[Figure: see text].

Whey protein preloading can alleviate stress adaptation disorder and improve hyperglycemia in women with gestational diabetes mellitus.

AIMS: To investigate the change of stress hormones, oxidative stress and insulin resistance (IR) in women with gestational diabetes mellitus (GDM) after supplement whey protein, in an attempt to gain insights into the prevention and treatment of GDM. MATERIALS AND METHODS: 60 GDM women were recruited in this study, and 30 women received a preload drink containing 20 g whey protein as group GDM-W, and the other 30 women received control flavoring drink as group GDM, and the trial lasted for 14 days. Plasma epinephrine (E), noradrenaline (NE), and cortisol were detected; we also determined levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH). Homeostasis model assessment of insulin resistance (HOMA-IR) was used to assess IR. RESULTS: In the GDM-W group, postprandial blood glucose was decreased significantly on 3, 5, 7, and 14 days (all p < .05), plasma 2 h insulin was increased by 7.2, 8.6, and 20.5% on days 5, 7, and 14 (p < .05, .05, .01). HOMA-IR was decreased significantly on day 14 (p < .05). MDA was decreased by 20.7% on day 14 (p < .01), and anti-oxidative enzymes' SOD was decreased by 13.4% on day 14 (p < .05) and GSH was decreased by 16.7 and 29.1% on days 7 and 14 (both p < .05). Stress hormones E and cortisol were decreased by 10.8 and 19.8%, respectively, on day 14 (p < .05). There was no significant difference in NE between the two groups within 14 days. CONCLUSIONS: Whey protein supplementation may improve hyperglycemia by alleviating stress disorder and oxidative stress injury in GDM women. This trial was registered at chictr.org.cn/as ChiCTR1800020413.

Rehabilitation training improves cognitive disorder after cerebrovascular accident by improving BDNF Bcl-2 and Bax expressions in regulating the JMK pathway.

OBJECTIVE: To explore the effect of rehabilitation training on cognitive impairment after cerebrovascular accident and its potential mechanism. PATIENTS AND METHODS: 100 patients of cerebrovascular accident treated in our hospital from August 2018 to August 2019 were selected as the subjects, and 50 patients with physical examination were selected as healthy control group. The patients with cerebrovascular accident were randomly divided into control group (50 patients) and research group (50 patients). The patients in the control group were given routine medication, the patients in research group were given rehabilitation training on the basis of routine drug therapy. The blood samples were collected on admission and 6 months after admission to detect the molecular markers related to inflammation, nerve cell nutrition and function and apoptosis in the serum. The cognitive function was evaluated by scales. We established a rat cerebral ischemia model, compared the differences in the evasive latency, serum CRP, BNDF, Bcl-2, BAX, Glu, NE levels and BNDF, TrkB, pTrkB, JNK levels in hippocampus, amygdala, and prefrontal tissue between model rats after rehabilitation training and model rats without rehabilitation training. RESULTS: On admission, there were no significant differences in the scores of Barthel index (BI), Fugl-Meyer motor function scale (FM), Montreal cognitive assessment scale (MoCA) and mini-mental state examination (MMSE) (p>0.05). 6 months later, the above scores and BNDF, Bcl-2, and norepinephrine were significantly higher in the research group (p<0.05), while CRP, Bax, 5-HT and glutamate in the research group were significantly lower than those in the control group (p<0.05). CONCLUSIONS: Rehabilitation training can improve the motor function, mental state and cognitive level of patients, reduce the levels of neurotoxic factors, pro-inflammatory factors and pro-apoptotic factors, and improve the levels of inhibiting apoptotic factors, neurotrophic factors and neurotransmitters. In animal experiments, rehabilitation training can increase BDNF and its activated receptors in hippocampus, amygdala and prefrontal lobe of rats, and decrease JNK of apoptotic protein, suggesting that rehabilitation training may regulate the expression of apoptotic proteins Bcl-2 and Bax by upregulating BDNF and its receptors and acting on JNK pathway, thereby inhibiting cell apoptosis and improving cognitive impairment after cerebrovascular accident.