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Background: Resolution of sleep disordered breathing (SDB) in typically developing children normalises heart rate variability (HRV), a measure of autonomic control, to that of non-snoring controls. Children with Down Syndrome (DS) have dampened heart rate variability (HRV) but the effect of treatment is not known. To assess the effect of improvement of SDB on autonomic control we compared HRV in children with DS whose SDB improved over 2 y, to those whose SDB did not improve., Methods: 24 children (3-19 y) had a baseline and follow-up polysomnographic study 2 y later. Improved SDB was defined as a reduction in obstructive apnea hypopnea index (OAHI) to ≤ 50% of baseline. Children were grouped into Improved (n = 12) and Unimproved (n = 12). Power spectral analysis of the ECG determined low frequency (LF), high frequency (HF) power and the LF/HF ratio. Seven children in the Improved and 2 in the Unimproved group were treated following the baseline study., Results: In the Unimproved group at follow-up, LF power was lower compared to baseline during N3 and Total Sleep (p < 0.05 for both). HF power was lower during REM (p < 0.05). HRV remained unchanged between studies in the Improved group., Conclusion: Autonomic control worsened as indicated by lower LF and HF power in children whose SDB was not improved. In contrast, in those children with improved SDB, autonomic control remained the same, suggesting improvement in SDB severity prevents further worsening of autonomic control in children with DS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Paroxysmal sympathetic hyperactivity (PSH) and catecholamine surge, which are associated with poor outcome, may be triggered by traumatic brain injury (TBI).β Adrenergic receptor blockers (β-blockers), as potential therapeutic agents to prevent paroxysmal sympathetic hyperactivity and catecholamine surge, have been shown to improve survival after TBI. The principal aim of this study was to investigate the effect of β-blockers on outcomes in patients with TBI., Methods: For this systematic review and meta-analysis, we searched MEDLINE, EMBASE, and Cochrane Library databases from inception to September 25, 2020, for randomized controlled trials, nonrandomized controlled trials, and observational studies reporting the effect of β-blockers on the following outcomes after TBI: mortality, functional measures, and cardiopulmonary adverse effects of β-blockers (e.g., hypotension, bradycardia, and bronchospasm). With use of random-effects model, we calculated pooled estimates, confidence intervals (CIs), and odds ratios (ORs) of all outcomes., Results: Fifteen studies with 12,721 patients were included. Exposure to β-blockers after TBI was associated with a significant reduction in adjusted in-hospital mortality (OR, 0.39; 95% CI, 0.30-0.51; I2 = 66.3%; p < 0.001). β-Blockers significantly improved the long-term (≥6 months) functional outcome (OR, 1.75; 95% CI, 1.09-2.80; I2 = 0%; p = 0.02). Statistically significant difference was not seen for cardiopulmonary adverse events (OR, 0.91; 95% CI, 0.55-1.50; I2 = 25.9%; p = 0.702)., Conclusion: This meta-analysis demonstrated that administration of β-blockers after TBI was safe and effective. Administration of β-blockers may therefore be suggested in the TBI care. However, more high-quality trials are needed to investigate the use of β-blockers in the management of TBI., Level of Evidence: Systematic review and meta-analysis, level III., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Using previous total mesorectal excision with pelvic autonomic nerve preservation (PANP+TME) and simple total mesorectal excision (TME) without emphasis on retained nerves as control, we explore the advantages of nerve plane-oriented laparoscopic total mesorectal excision (NPO+LTME) on urinary and sexual function. Methods: A retrospective cohort study was carried out. Case inclusion criteria: (1) male patients with pathologically confirmed middle and low rectal adenocarcinoma (4 to 11 cm from the anus); (2) stage T1-2tumor; (3) normal sexual life before operation. Exclusion criteria: (1) no pathological diagnosis before surgery; (2) local recurrence or distant metastasis; (3) preoperative neoadjuvant chemoradiotherapy; (4) opensurgery and laparoscopic surgery conversionto open; (5) no follow-up data. According to the above criteria, clinical data of 173 male patients with low and middle rectal adenocarcinoma who underwent radical operation for laparoscopic rectal cancer from July 2003 to July 2018 at the Department of Gastrointestinal Surgery, Wuhan University People's Hospital were collected. According to different surgical methods, patients were divided into TME group (58 cases), PANP+TME group (63 cases) and NPO+LTME group (52 cases). There were no significant differences in the baseline data including age, body mass index and pathological examination between the 3 groups (all P >0.05). The nerve plane referred to the nerve, the adipose tissue, the extremely finecapillaries around the nerve with overlying fine membranous tissue. NPO+LTME referred to the process of laparoscopic TME guided by the nerve plane, performing in the loose connective tissue between the nerve plane and the rectal properfascia, in order to ensure the integrity of the nerve plane, and maximally protect the patient's urinary and reproductive functions. The operation time, intraoperative blood loss, urinary catheter removal time, urinary function grading, postoperative first erection time, and erectile function and ejaculation function were observed and compared among the 3 groups at 3- and 6-month after operation. Results: In the NPO+LTME group, the PANP+TME group and the TME group, the operation time was (181.9±24.5) minutes, (176.7±29.2) minutes and (137.7±16.2) minutes, respectively ( F =54.868, P <0.001); the intraoperative blood lost was (6.0±1.4) ml, (6.5±1.8) ml and (12.8±4.6) ml, respectively ( F =95.016, P <0.001); the time to postoperative removal of the catheter was (2.4±1.1) days, (3.7 ±1.7) days and (6.5±2.4) days, respectively ( F =79.409, P <0.001); the first postoperative erection time was (1.6±0.6) days, (8.9±2.7) days and (15.9±6.8) days ( F =177.677, P <0.001), respectively, whose differences were all statistically significant (all P <0.01). In comparison of urinary function grading, the proportion of grade I (normal function, no urinary dysfunction) in the NPO+LTME, the ANP+TME group and the TME group was 84.1% (53/63), 39.7% (23/58) and 19.2% (10/52), respectively, and the difference was statistically significant ( H =52.915, P <0.001). At postoperative 3- and 6-month, proportion of patients with grade I erectile function (normal erectile function) was 77.8% (49/63) and 85.7% (54/63), 44.8% (26/58) and 53.4% (31/58), 28.8% (15/52) and 48.1% (25/52) in the NPO+LTME group, the PANP+TME group, and the TME group, respectively. The differences were statistically significant ( H =91.709, P <0.001; H =79.692, P <0.001). The proportion of patients with grade I ejaculation function (with ejaculation, no abnormalities in routine semen examination before and after surgery) at 3- and 6-month after surgery in the NPO+LTME group, the PANP+TME group and the TME group was 82.5% (52/63) and 87.3% (55/63), 53.4% (31/58) and 60.3% (35/58), 28.8% (15/52) and 46.1% (24/52), respectively. The differences were statistically significant as well ( H =86.543, P <0.001; H =78.667, P <0.001). Patients in the NPO+LTME group had no grade III erections and ejaculation disorders. Conclusion: The surgical procedure of NPO+LTME can promote the recovery of postoperative neurological function and preserve urination and sexual function better.

Background: The aim of this study was to compare the effects of dexmedetomidine, esmolol, and combination of both on control of sympathetic response to laryngoscopy and tracheal intubation in coronary artery disease patients., Material and Methods: A prospective, randomized, double-blinded clinical study included 90 patients scheduled for elective coronary artery bypass surgery. Patients were randomly allocated into three groups of 30 each: dexmedetomidine group (Group D) 1 μg/kg, esmolol group (Group E) 2 mg/kg, and group dexmedetomidine with esmolol (Group DE) 0.5 μg/kg of dexmedetomidine with 1 mg/kg of esmolol. Each drug was diluted with 0.9% normal saline to 20 ml volume and infused in 10 min before induction of anesthesia. Hemodynamic changes (heart rate [HR], arterial blood pressure, and pulmonary artery pressure) were compared at various time intervals as follows-baseline, after study drug, after induction, and 1, 3, and 5 min after intubation. Statistical analysis included analysis of variance, Chi-square, and Fisher's exact test., Results: In Group DE, there was no significant increase in HR at all-time intervals, and the HR was stable compared to Group D and Group E. Blood pressure values were comparable in all groups except in Group E at 5 min. The pulmonary arterial pressures were statistically less in DE group except at 3 and 5 min., Conclusions: The combination of dexmedetomidine and esmolol group has beneficial effect on HR and pulmonary arterial pressures but has no additional advantage with respect to arterial blood pressure when compared with dexmedetomidine and esmolol groups in patients undergoing elective coronary artery bypass grafting.

Exercise is a fundamental component of diabetes management. However, choosing inappropriate type or timing of exercise is associated with mild or severe hypoglycemia either during exercise or several hours after exercise. Several studies have shown that impaired counterregulatory responses triggers hypoglycemia. Therefore, in this investigation, we explored the appropriate intensity and time of exercise in patients with diabetes. The mechanisms of counterregulatory responses and hypoglycemia associated autonomic failure (HAAF), as well as the strategies for preventing episodes of hypoglycemia after exercise were also investigated. In this study, we obtained the following results: 1) High intensity interval exercise is more suitable for diabetic patients. 2) Morning exercise reduces nocturnal hypoglycemia risks compared with midday, afternoon and evening exercise. 3) Hypoglycemia can be prevented by dietary approach, reduction or suspension of insulin dose, use of mini dose glucagon, caffeine, mitigation methods, prediction algorithm, autonomic feedback controlled close-loop insulin delivery, real time continuous glucose monitoring. Based on these results we concluded that exercise may cause severe hypoglycemia or induce blunted response in patients with diabetes. For Diabetes Mellitus (DM) patients, the intensity and time of exercise influence the occurrence of hypoglycemia. This review summarizes the clinical characteristics of different types of exercises and time of exercise that can be potentially used to educate and guide patients regarding the role of exercise in standard of care.

Calcitonin gene-related peptide (CGRP) can cause migraines, yet it is also a potent vasodilator that protects against hypertension. Given the emerging role of CGRP-targeted antibodies for migraine prevention, an important question is whether the protective actions of CGRP are mediated by vascular or neural CGRP receptors. To address this, we have characterized the cardiovascular phenotype of transgenic nestin/hRAMP1 mice that have selective elevation of a CGRP receptor subunit in the nervous system, human receptor activity-modifying protein 1 (hRAMP1). Nestin/hRAMP1 mice had relatively little hRAMP1 RNA in blood vessels and intravenous injection of CGRP caused a similar blood pressure decrease in transgenic and control mice. At baseline, nestin/hRAMP1 mice exhibited similar mean arterial pressure, heart rate, baroreflex sensitivity, and sympathetic vasomotor tone as control mice. We previously reported that expression of hRAMP1 in all tissues favorably improved autonomic regulation and attenuated hypertension induced by angiotensin II (Ang II). Similarly, in nestin/hRAMP1 mice, hypertension caused by Ang II or phenylephrine was greatly attenuated, and associated autonomic dysregulation and increased sympathetic vasomotor tone were diminished or abolished. We conclude that increased expression of neuronal CGRP receptors is sufficient to induce a protective change in cardiovascular autonomic regulation with implications for migraine therapy.

Heart failure is a common adverse effect associated with doxorubicin treatment. The aim of this study is to investigate the effect of ivabradine treatment on doxorubicin-induced heart failure in conscious rats. Rats were treated with doxorubicin (2.5 mg/kg/d) or ivabradine (10 mg/kg/d) alone or along with doxorubicin injections. Changes in heart rate variability (HRV), baroreflex sensitivity, left ventricular (LV) function, serum cardiac troponin T, and cardiac histological features were taken as index parameters for the development of heart failure. Ivabradine significantly reduced the elevated heart rate; normalized the parameters of LV function, dP/dtmax and the relaxation time constant (Tau); reduced the elevated serum level of cardiac troponin T; and minimized the cardiac structural abnormalities in doxorubicin-treated rats. Moreover, ivabradine significantly increased the diminished time domain parameters of HRV, SDNN and rMSSD, and decreased the elevated low frequency power and the low frequency/high frequency while having no effect on the reduced high frequency power. Consistently, ivabradine significantly lowered the elevated baroreflex sensitivity measured by sodium nitroprusside. In conclusion, ivabradine ameliorated the LV dysfunction induced by doxorubicin. Moreover, ivabradine increased the overall HRV and restored the autonomic balance by reducing the sympathetic over activation. Therefore, ivabradine may have a possible therapeutic potential against doxorubicin-induced heart failure.

Extracorporeal membrane oxygenation (ECMO) is used in critically ill patients with severe pulmonary and/or cardiac failure. Blood is drained from the venous system and pumped through a membrane oxygenator where it is oxygenated. For pulmonary support, the blood is returned to the patient via a vein (veno-venous ECMO) and for pulmonary/circulatory support it is returned via an artery (veno-arterial ECMO).Veno-venous ECMO can be performed either with a single dual-lumen cannula or with two separate single-lumen cannulas. If the latter is chosen, flow direction can either be from the inferior caval vein (IVC) to the right atrium or the opposite. Earlier research has shown that drainage from the IVC yields less recirculation and therefore the IVC to right atrium route has become the standard in most centers for veno-venous ECMO with two cannulas. However, recent research has shown that recirculation can be minimized using a multistage draining cannula in the optimal position inserted via the right internal jugular vein and with blood return to the femoral vein. The clinical results with this route are excellent.In veno-arterial ECMO the most common site for blood infusion is the femoral artery. If venous blood is drained from the IVC, the patient is at risk of developing a dual circulation (Harlequin syndrome, North-South syndrome, differential oxygenation) meaning a poor oxygenation of the upper part of the body, while the lower part has excellent oxygenation. By instead draining from the superior caval vein (SVC) via a multistage cannula inserted in the right internal jugular vein this risk is neutralized.In conclusion, the authors argue that draining blood from the SVC and right atrium via a multistage cannula inserted in the right internal jugular vein is equal or better than IVC drainage both in veno-venous two cannula ECMO and in veno-arterial ECMO with blood return to the femoral artery.

Introduction: Familial amyloid polyneuropathy (FAP) is a rare disease caused by systemic deposition of amyloidogenic variants of the transthyretin (TTR) protein. The TTR-V30M mutation is caused by the substitution of valine by methionine at position 30 and mainly affects the peripheral and autonomic nervous systems. Cardiovascular manifestations are common and are due to autonomic denervation and to amyloid deposition in the heart. Cardiac sympathetic denervation detected by iodine-123 labeled metaiodobenzylguanidine (MIBG) is an important prognostic marker in TTR-V30M FAP. Liver transplantation, widely used to halt neurological involvement, appears to have a varying effect on the progression of amyloid cardiomyopathy. Its effect on the progression of cardiac denervation remains unknown., Methods: In this observational study, patients with the TTR-V30M mutation underwent annual cardiac assessment and serial MIBG imaging with quantification of the late heart-to-mediastinum (H/M) ratio., Results: We studied 232 patients (median age 40 years, 54.7% female, 37.9% asymptomatic at the time of inclusion) who were followed for a median of 4.5 years and underwent a total of 558 MIBG scans. During follow-up, 47 patients (20.3%) died. MIBG scintigraphy at inclusion was a strong predictor of prognosis, with the risk of death increasing by 27.8% for each one-tenth reduction in the late H/M ratio. The late H/M ratio decreased with age (0.082/year, p<0.001), but progression of cardiac denervation was so slow that annual repetition of MIBG imaging did not increase its prognostic accuracy. During follow-up, 70 symptomatic patients underwent liver transplantation. The late H/M ratio decreased by 0.19/year until transplantation but no statistically significant differences were detected after the procedure., Conclusions: Cardiac denervation is common during the progression of TTR-V30M FAP and quantification of the late H/M ratio on MIBG scintigraphy is valuable for prognostic stratification of these patients. Liver transplantation stabilizes cardiac denervation, without recovery or further deterioration in cardiac MIBG uptake after the procedure., (Copyright © 2017 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: In rectopexy the use of meshes provides stability by mechanical support as well as by the induction of scar formation; however, one of the problems of conventional methods of mesh rectopexy is that many patients postoperatively suffer from functional disorders, such as fecal incontinence and stool evacuation disorders. One reason is the damage of vegetative nerves following dorsal and lateral mobilization of the rectum, which is required for positioning of the mesh. In 2004 D'Hoore and Penninckx first described the method of ventral rectopexy, a new technique of mesh rectopexy which allows preservation of the autonomic nerves., Objective: Does ventral rectopexy provide advantages regarding functional outcome, complications and recurrence rates?, Material and Methods: A search was carried out in the databases PubMed and Medline for studies on ventral rectoplexy. Presentation and analysis of the current state of relevant studies relating to ventral rectopexy., Results: Ventral rectopexy is characterized by a low complication rate and good functional results in terms of improvement of incontinence, constipation and stool evacuation disorders. The indications for ventral rectopexy are considered in patients with external prolapse of the rectum. Also in a well-selected patient population internal prolapse, rectocele as well as enterocele accompanied by obstructive defecation syndrome represent relative indications for ventral rectopexy., Conclusion: In order to obtain a valid assessment of the value of this procedure it is crucial to improve the current lack of evidence (level 3) by prospective randomized studies that compare ventral rectopexy with other surgical techniques and nonsurgical treatment options.

Autonomic nervous system (ANS) imbalances are involved in the etiology of cancer, allergy, and collagen diseases. Previously, we hypothesized that FoxO and HSF-1 limit autonomic stress responses via negative feedback on the ANS. Here, we evaluated the role of AKT, a negative regulator of FoxO, during activation of the ANS by loneliness stress in mice. Spontaneous motility was increased during loneliness stress and decreased after release from stress. The AKT activator SC79 attenuated stress-induced spontaneous motility, whereas the AKT inhibitor API-2 prevented decreases in motility after stress release. Our results show that AKT activity regulates ANS responses to loneliness stress., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To examine whether cardiovascular autonomic neuropathy (CAN) is an independent risk factor of cardiovascular disease (CVD) events during DCCT/EDIC., Research Design and Methods: Standardized cardiovascular autonomic reflex tests (R-R response to paced breathing, Valsalva maneuver, postural changes in blood pressure) were performed at DCCT baseline, every 2 years throughout DCCT, and at two time points in EDIC. CVD events were ascertained throughout the study and adjudicated by a review committee. Cox proportional hazards models were used to estimate the effect of CAN at DCCT closeout on subsequent CVD risk., Results: There were 299 adjudicated CVD events in 165 participants following the DCCT closeout assessment: 132 of 1,262 subjects (10%) without CAN at DCCT closeout who experienced 244 CVD events versus 33 of 131 subjects (25%) with CAN at DCCT closeout who experienced 55 events (hazard ratio 2.79, 95% CI 1.91-4.09 for time to first CVD event). The cumulative incidence of the first occurrence of any CVD event during EDIC was significantly higher in participants with CAN at DCCT closeout compared with those without CAN. The association remained marginally significant after adjustment for multiple risk factors, including the EDIC updated mean HbA 1c . When analyzed as a continuous variable, R-R variation was significantly lower at DCCT closeout in participants who experienced a CVD event compared with those who did not (P = 0.0012)., Conclusions: In the DCCT/EDIC cohort, individuals diagnosed with CAN at DCCT closeout experienced a higher long-term risk of CVD events during follow-up in EDIC. This association was not independent of historic glycemic exposure and its metabolic memory effect, the principal determinant of both long-term CVD risk and CAN in type 1 diabetes., (© 2017 by the American Diabetes Association.)

High work stress has been consistently associated with disturbed autonomic balance, specifically, lowered vagal cardiac control and increased sympathetic activity, which may lead to increased cardiovascular risk. Stress management procedures have been proposed to reduce autonomic dysfunctions related to work stress in different categories of workers exposed to heightened work demands, while a limited number of studies addressed this issue in managers. The present study was aimed at evaluating the effectiveness of a respiratory sinus arrhythmia (RSA) biofeedback (BF) intervention on psychological and physiological outcomes, in managers with high-level work responsibilities. Thirty-one managers leading outstanding private or public companies were randomly assigned to either a RSA-BF training (RSA-BF; N = 16) or a control group (N = 15). The RSA-BF training consisted of five weekly 45 min sessions, designed to increase RSA, whereas controls had to provide a daily stress diary once a week. After the training, managers in both groups reported reduced heart rate at rest, lower anxiety levels and improvement in health-related quality of life. More importantly, managers in the RSA-BF group showed increased vagal control (as indexed by increased RSA), decreased sympathetic arousal (as indexed by reduced skin conductance and systolic blood pressure) and lower emotional interferences, compared to managers in the control group. Results from this study showed that RSA-BF training was effective in improving cardiac autonomic balance at rest. Moreover, findings from this study underline the effectiveness of biofeedback in reducing psychophysiological negative outcomes associated with stress in managers.

Chronic musculoskeletal pain (CMP) conditions, like fibromyalgia, are associated with widespread pain and alterations in autonomic functions. Regular physical activity prevents the development of CMP and can reduce autonomic dysfunction. We tested if there were alterations in autonomic function of sedentary mice with CMP, and whether exercise reduced the autonomic dysfunction and pain induced by CMP. Chronic musculoskeletal pain was induced by 2 intramuscular injections of pH 5.0 in combination with a single fatiguing exercise task. A running wheel was placed into cages so that the mouse had free access to it for either 5 days or 8 weeks (exercise groups) and these animals were compared to sedentary mice without running wheels. Autonomic function and nociceptive withdrawal thresholds of the paw and muscle were assessed before and after induction of CMP in exercised and sedentary mice. In sedentary mice, we show decreased baroreflex sensitivity, increased blood pressure variability, decreased heart rate variability, and decreased withdrawal thresholds of the paw and muscle 24 hours after induction of CMP. There were no sex differences after induction of the CMP in any outcome measure. We further show that both 5 days and 8 weeks of physical activity prevent the development of autonomic dysfunction and decreases in withdrawal threshold induced by CMP. Thus, this study uniquely shows the development of autonomic dysfunction in animals with chronic muscle hyperalgesia, which can be prevented with as little as 5 days of physical activity, and suggest that physical activity may prevent the development of pain and autonomic dysfunction in people with CMP.

The Diabetes Control and Complications Trial (DCCT) and its epidemiological follow-up, the Epidemiology of Diabetes Interventions and Complications (EDIC) provide important insight on the natural history of distal symmetrical polyneuropathy and cardiovascular autonomic neuropathy in patients with type 1 diabetes and on the impact of intensive treatment of hyperglycemia on disease progression. This chapter summarizes the design and methods used for neuropathy evaluations both in the DCCT and in EDIC, the characteristics of the DCCT/EDIC patient population, and summarizes the findings of the DCCT/EDIC relative to neuropathic complications of type 1 diabetes. Lessons learned from the DCCT and EDIC experiences of longitudinal assessments of neuropathic complications are also reviewed., (© 2016 Elsevier Inc. All rights reserved.)

Introduction: The anti-atrial fibrillation (AF) effects of GS-458967 (GS-967), a selective, potent inhibitor of cardiac late Na(+) current (I(Na)), were evaluated in a novel model of AF induction that does not require electrical stimuli., Methods and Results: In 6 closed-chest anesthetized pigs, AF was induced by intrapericardial acetylcholine (1 mL of 100 mM solution) followed within 1 minute by epinephrine (20 μg/kg, i.v., bolus over 1 min). Effects of GS-967 (0.4 mg/kg, i.v., infused over 30 min) on inducibility and duration of AF were analyzed. Administration of acetylcholine followed by epinephrine elicited spontaneous AF that persisted for 12.03 ± 1.22 minutes (mean ± SEM) in all 6 pigs. Following GS-967, AF did not occur in 5 of 6 pigs when plasma concentration was 383 ± 150 nM. In the single animal in which AF could still be induced, the arrhythmia lasted 6.3 minutes. Partial return of AF inducibility occurred in 2 of 6 animals at 90 minutes, when plasma concentration of GS-967 was 228 ± 35 nM. GS-967 reduced the QT interval (P = 0.004), consistent with cardiac late I(Na) inhibition, but did not affect heart rate, mean arterial pressure, QRS duration, or PR interval. Epinephrine infusion alone, tested in a separate group (N = 6), did not provoke AF., Conclusion: Selective cardiac late I(Na) inhibition with GS-967 suppresses spontaneous induction of AF in a novel model that does not require provocative electrical stimuli. Because this mode of action has only a mild on effect on contractility, it offers an advantage over contemporary anti-AF agents, which can have negative inotropic actions., (© 2015 Wiley Periodicals, Inc.)

Background: This study assesses the autonomic function of patients who have regained awareness of hypoglycaemia following islet cell or whole pancreas transplant., Methods: Five patients with type 1 diabetes and either islet cell (four patients) or whole pancreas (one patient) transplant were assessed. These patients were age-matched and gender-matched to five patients with type 1 diabetes without transplant and preserved hypoglycaemia awareness and five healthy control participants without diabetes. All participants underwent (i) a battery of five cardiovascular autonomic function tests, (ii) quantitative sudomotor axonal reflex testing, and (iii) sympathetic skin response testing., Results: Total recorded hypoglycaemia episodes per month fell from 76 pre-transplant to 13 at 0- to 3-month post-transplant (83% reduction). The percentage of hypoglycaemia episodes that patients were unaware of decreased from 97 to 69% at 0-3 months (p < 0.001, Fisher's exact test) and to 20% after 12 months (p < 0.0001, Fisher's exact test). This amelioration was maintained at the time of testing (mean time: 4.1 years later, range: 2-6 years). Presence of significant autonomic neuropathy was seen in all five transplanted patients (at least 2/3 above modalities abnormal) but in only one of the patients with diabetes without transplantation., Conclusions: The long-term maintenance of hypoglycaemia awareness that returns after islet cell/pancreas transplantation in patients with diabetes is not prevented by significant autonomic neuropathy and is better accounted for by other factors such as reversal of hypoglycaemia-associated autonomic failure., (Copyright © 2015 John Wiley & Sons, Ltd.)

Objective: Complete prevention of diabetic neuropathies has not been previously demonstrated. We sought to determine whether long-term near-normoglycaemia maintained from the diagnosis of type 1 diabetes is associated with polyneuropathy and cardiac autonomic dysfunction., Design: Prospective observational study over 24 years., Setting: Ambulatory care., Participants: 32 newly diagnosed patients with type 1 diabetes aged 20.3 ± 1.0 years, duration of diabetes 2.7 ± 0.3 weeks., Intervention: Insulin therapy according to standards of care., Primary and Secondary Outcome Measures: Motor and sensory nerve conduction velocity (MNCV and SNCV), heart rate variability (HRV), and confirmed clinical polyneuropathy measured at 15 time points over 24 years and quantitative sensory testing (QST) determined over 20-22 years., Results: 11 patients were well controlled over 24 years with mean glycated haemoglobin (HbA1c) <7.0% (6.5 ± 0.1%; group 1), whereas 21 patients were poorly controlled (mean HbA1c ≥ 7.0%: 8.3 ± 0.2%; group 2). After 24 years, MNCV was faster in group 1 versus group 2 in the median (55.5 ± 1.6 vs 48.9 ± 1.6 m/s), ulnar (56.5 ± 1.5 vs 49.3 ± 1.7 m/s) and peroneal nerve (44.7 ± 1.6 vs 36.8 ± 2.5 m/s), while SNCV was faster in the median (53.6 ± 1.6 vs 45.5 ± 2.8 m/s), ulnar (54.7 ± 1.8 vs 43.0 ± 3.9 m/s), and sural nerve (44.5 ± 1.8 vs 35.5 ± 2.6 m/s; all p<0.05). The annual decline in peroneal MNCV and sural SNCV in group 1 was sixfold and threefold faster in group 2 than in group 1, respectively. Likewise, impairment in QST and HRV developed at faster rates in group 2. After 24 years, 64% of patients in group 2, but none in group 1, developed confirmed clinical polyneuropathy., Conclusions: Near-normoglycaemia maintained from the diagnosis of type 1 diabetes over 24 years was associated with a complete prevention of the decline in hyperglycaemia-related peripheral and autonomic nerve function, and development of confirmed clinical polyneuropathy., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Earlier, we found that arsenic induced cholinergic deficits in rat brain could be protected by curcumin. In continuation to this, the present study is focused to unravel the molecular mechanisms associated with the protective efficacy of curcumin in arsenic induced cholinergic deficits. Exposure to arsenic (20mg/kg body weight, p.o) for 28 days in rats resulted to decrease the expression of CHRM2 receptor gene associated with mitochondrial dysfunctions as evident by decrease in the mitochondrial membrane potential, activity of mitochondrial complexes and enhanced apoptosis both in the frontal cortex and hippocampus in comparison to controls. The ultrastructural images of arsenic exposed rats, assessed by transmission electron microscope, exhibited loss of myelin sheath and distorted cristae in the mitochondria both in the frontal cortex and hippocampus as compared to controls. Simultaneous treatment with arsenic (20mg/kg body weight, p.o) and curcumin (100mg/kg body weight, p.o) for 28 days in rats was found to protect arsenic induced changes in the mitochondrial membrane potential and activity of mitochondrial complexes both in frontal cortex and hippocampus. Alterations in the expression of pro- and anti-apoptotic proteins and ultrastructural damage in the frontal cortex and hippocampus following arsenic exposure were also protected in rats simultaneously treated with arsenic and curcumin. The data of the present study reveal that curcumin could protect arsenic induced cholinergic deficits by modulating the expression of pro- and anti-apoptotic proteins in the brain. More interestingly, arsenic induced functional and ultrastructural changes in the brain mitochondria were also protected by curcumin., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Jo Ireland of the Animal Health Trust describes a new field trial of a potential vaccine against equine grass sickness., (British Veterinary Association.)

We report the development of hypothermia in a patient with Hodgkin lymphoma which resolved with chemotherapy administration. A review of the literature revealed 16 previous reports of hypothermia in patients with Hodgkin lymphoma. Overall prognosis seems to be unfavorable. To the best of our knowledge this is the first report of hypothermia in a patient with Hodgkin lymphoma transforming from chronic lymphocytic leukemia (Richter's syndrome). A possible pathophysiology could be paraneoplastic autonomic neuropathy. Physicians should be aware that Hodgkin lymphoma can present with hypothermia and should carefully monitor newly diagnosed patients with advanced disease for this complication. Likewise, patients with Hodgkin lymphoma who develop hypothermia should be screened for signs of autonomic neuropathy.

Background: There are conflicting data regarding the effects of renal transplantation (RT) on uraemic autonomic dysfunction. Moreover, no study has examined the impact of physical training on the cardiac autonomic function in RT patients. Thus, we studied the effects of exercise training on heart rate variability (HRV) and arterial baroreflex sensitivity (BRS), which are sensitive markers of cardiac autonomic outflow, in RT recipients., Methods: Eleven patients (Exercise group-aged 52.1 ± 5.6 years) were studied before and after 6 months of exercise training. Twelve age- and sex- matched RT patients (Sedentary) and 12 healthy sedentary individuals (Healthy), who remained untrained, served as controls. At baseline and follow-up, all the subjects underwent cardiopulmonary exercise testing for the evaluation of peak oxygen consumption (VO2peak), a tilt test for the evaluation of BRS and baroreflex effectiveness index (BEI) and an ambulatory 24-h Holter monitoring for time- and frequency-domain measures of HRV., Results: In the exercise group, VO2peak increased by 15.8% (P < 0.05) and all depressed HRV and BRS indices were significantly improved after training. Specifically, the standard deviation of all normal-to-normal (NN) intervals (SDNN) significantly increased by 92.5%, the root-mean-square of the differences between consecutive NN intervals by 45.4%, the percentage value of NN50 count by 58.2%, the high-frequency by 74.8% and low-frequency spectral power by 41.6%, BRS by 43.7% and BEI by 57.3%. None of the variables studied was altered over time in either control group., Conclusions: The increased cardiorespiratory fitness by exercise training was associated with an improved BRS function and a modification of the sympathovagal control of HRV towards a persistent increase in parasympathetic tone. These alterations may lead to a better cardiovascular prognosis in RT recipients.

Introduction: Autonomic dysfunction, including orthostatic hypotension (OH), sialorrhea, sexual dysfunction, urinary dysfunction and constipation is a common feature of Parkinson's disease (PD). Even though its treatment has been recognized as a major unmet need in PD, there is a paucity of clinical trials to assess their treatment., Areas Covered: Evidence about the efficacy and safety of available treatments for autonomic dysfunction is summarized. Potential targets for upcoming therapies are then discussed in light of what is currently known about the physiopathology of each disorder in PD. Proof-of-concept trials and circumstantial evidence about treatments for autonomic dysfunction as well as upcoming clinical trials are discussed. Finally, critical aspects of clinical trials design are considered., Expert Opinion: Botulinum toxin (BTX) or glycopyrrolate might be used for sialorrhea whereas macrogol could be useful in constipation. There is preliminary evidence suggesting that fludrocortisone, domperidone, droxidopa or fipamezole may be effective for the treatment of OH. Tropicamide, clonidine or radiotherapy are under development for sialorrhea. Sildenafil may be effective for the treatment of erectile dysfunction; BTX or behavioral therapy for urinary incontinence and lubiprostone and probiotics for constipation. Sound clinical trials are needed in order to allow firm evidence-based recommendations about these treatments.

Aims/hypothesis: There is limited evidence on how multifactorial treatment improves outcomes of diabetes when initiated in the lead time between detection by screening and diagnosis in routine clinical practice. Cardiac autonomic neuropathy (CAN) in people with diabetes indicates widespread damage to the autonomic nervous system, which may severely affect health and quality of life. We examined effects of early detection and subsequent intensive treatment of type 2 diabetes in primary care on the prevalence of CAN at the 6-year follow-up examination in a pragmatic cluster-randomised parallel group trial., Methods: One hundred and ninety general practices were randomised to deliver either intensive multifactorial treatment (IT) or routine care (RC) as recommended by national guidelines to patients with type 2 diabetes, identified through a stepwise screening programme in the primary care setting. 1533 people (IT, n = 910; RC, n = 623) were identified and included. At the 6-year follow-up examination, measures of CAN were applied in an unselected subsample of 777 participants using heart rate variability analysis and standard tests of CAN., Results: At the 6-year follow-up examination, the prevalence of early CAN was 15.1% in the RC group and 15.5% in the IT group, while manifest CAN was present in 7.1% and 7.3%, respectively. We found no statistically significant effect of intensive treatment on the prevalence of CAN compared with routine care., Conclusions/interpretation: In the Danish arm of the ADDITION Study, signs of CAN were highly prevalent 6 years after a screening-based diagnosis of type 2 diabetes. Intensive multifactorial treatment did not significantly affect the prevalence of CAN compared with routine care. However, at follow-up the level of medication was also high in the RC group.

Background and Aims: Portal hypertension causes arterial vasodilation and sympathetic atrophy in the splanchnic area. We aimed to demonstrate a relationship between hemodynamic alterations and sympathetic atrophy by investigating a pathway from sensitive afferent signals to mesenteric sympathetic ganglia., Methods: Experiments were conducted in sham and portal vein ligated (PVL) adult and neonatal rats treated with vehicle or capsaicin. Hemodynamic parameters, and immunohistochemistry, immunofluorescence and Western blot of different tissues were analysed., Results: cFos expression in the brain supraoptic nuclei was used to confirm abrogation of the afferent signal in capsaicin-treated PVL rats (effectively afferent blocked). Neonatal and adult PVL afferent blocked rats showed simultaneous prevention of hemodynamic alterations and sympathetic atrophy (measured by tyrosine hydroxylase expression in nerve structures of splanchnic vasculature). Not effectively afferent blocked rats showed none of these effects, behaving as PVL vehicle. All capsaicin treated animals presented loss of calcitonin gene-related peptide in superior mesenteric artery and ganglia, whereas neuronal nitric oxide synthase remained unaffected. Neuronal markers semaphorin-3A, nerve growth factor, its precursor and p75 neurotrophic receptor, were significantly over-expressed in the PVL sympathetic ganglia compared with sham, but not in effectively afferent blocked rats. Semaphorin-3A staining in mesenteric ganglia co-localized with vesicular acetylcholine transporter, but not with adrenergic, nitrergic and sensory axons, suggesting that semaphorin-3A might originate in preganglionic neurons., Conclusion: These results indicate that the nervous system has a central role in the genesis of the circulatory abnormalities of portal hypertension, and support that mesenteric sympathetic atrophy contributes to splanchnic arterial vasodilation., (© 2012 John Wiley & Sons A/S.)

Cardiovascular autonomic neuropathy (CAN) in diabetes is generally overlooked in practice, although awareness of its serious consequences is emerging. Challenges in understanding the complex, dynamic changes in the modulation of the sympathetic/parasympathetic systems' tone and their interactions with physiologic mechanisms regulating the control of heart rate, blood pressure, and other cardiovascular functions in the presence of acute hyper-or-hypoglycemic stress, other stressors or medication, and challenges with sensitive evaluations have contributed to lower CAN visibility compared with other diabetes complications. Yet, CAN is a significant cause of morbidity and mortality, due to a high-risk of cardiac arrhythmias, silent myocardial ischemia and sudden death. While striving for aggressive risk factor control in diabetes practice seemed intuitive, recent reports of major clinical trials undermine established thinking concerning glycemic control and cardiovascular risk. This review covers current understanding and gaps in that understanding of the clinical implications of CAN and prevention and treatment of CAN.

Autonomic dysfunction, including baroreceptor attenuation and sympathetic activation, has been reported in patients with myocardial infarction (MI) and has been associated with increased mortality. We tested the hypotheses that exercise training (ET) in post-MI patients would normalize arterial baroreflex sensitivity (BRS) and muscle sympathetic nerve activity (MSNA), and long-term ET would maintain the benefits in BRS and MSNA. Twenty-eight patients after 1 month of uncomplicated MI were randomly assigned to 2 groups, ET (MI-ET) and untrained. A normal control group was also studied. ET consisted of three 60-minute exercise sessions per week for 6 months. We evaluated MSNA (microneurography), blood pressure (automatic oscillometric method), heart rate (ECG), and spectral analysis of RR interval, systolic arterial pressure (SAP), and MSNA. Baroreflex gain of SAP-RR interval and SAP-MSNA were calculated using the α-index. At 3 to 5 days and 1 month after MI, MSNA and low-frequency SAP were significantly higher and BRS significantly lower in MI patients when compared with the normal control group. ET significantly decreased MSNA (bursts per 100 heartbeats) and the low-frequency component of SAP and significantly increased the low-frequency component of MSNA and BRS of the RR interval and MSNA. These changes were so marked that the differences between patients with MI and the normal control group were no longer observed after ET. MSNA and BRS in the MI-untrained group did not change from baseline over the same time period. ET normalizes BRS, low-frequency SAP, and MSNA in patients with MI. These improvements in autonomic control are maintained by long-term ET. These findings highlight the clinical importance of this nonpharmacological therapy based on ET in the long-term treatment of patients with MI.

We assessed the state of the autonomic nervous system in 90 children with diabetes mellitus type I. The autonomic dysfunction syndrome was found in 58,9% and diabetic cardiac autonomic neuropathy in 28,9% of patients. We revealed the high risk of the development of diabetic cardiac autonomic neuropathy in children with diabetes mellitus type I in the presence of the autonomic dysfunction syndrome. It has been shown that the early treatment of functional disturbances of the autonomic nervous system using transcranial magnetic stimulation is necessary to prevent the manifestation of diabetic cardiac autonomic neuropathy.

Background: We previously demonstrated that cyclosporine (CyA) impairs endothelial function as a result of alterations in nitric oxide (NO) and endothelin-1 (ET-1) regulation. Bosentan (BOS), an ET-1 antagonist, and tetrahydrobiopterin (BH₄), an eNOS cofactor, may reduce endothelial dysfunction by improving ET-1/NO homeostasis., Methods: Lewis rats received intraperitoneal injections of CyA with BOS or with BOS+BH₄ daily for 2 weeks. Control (Con) animals received saline injections. Thoracic aortic segments were assessed for endothelial-dependent (E(dep)) and -independent (E(ind)) relaxation (E(max%)) after exposure to acetylcholine and sodium nitroprusside. Vessel sensitivity to ET-1-induced vasospasm was evaluated., Results: CyA use resulted in impaired E(dep) vasorelaxation when compared with Con, whereas BOS and BH₄ treatment preserved E(dep) vasorelaxation. CyA significantly altered E(ind) vasorelaxation, whereas BOS and BH₄ therapy attenuated CyA-induced effects. Compared with Con, CyA and BH₄ exposure demonstrated increased sensitivity to ET-1 vasospasm. BOS therapy abrogated the CyA and BH₄-induced sensitivity to vasospasm. CyA treatment resulted in higher 8-isoprostane levels compared with Con. CyA-mediated vascular dysfunction is characterized by impaired NO and ET-1 homeostasis., Conclusions: Our study suggests potential therapeutic strategies to prevent endothelial dysfunction as combined therapy with ET-1 antagonism and NO augmentation completely abrogated CyA-induced vascular injury., (Copyright © 2011 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Diabetic autonomic neuropathy is a critical complication frequently encountered in anaesthetic and surgical practice. Power spectral analysis is a noninvasive tool for monitoring frequency analysis of heart rate variability (HRV) and autonomic control of the heart. This study examined HRV changes in preoperative diabetic patients without overt signs of autonomic dysfunction and in matched controls (n=18 per group). HRV values at -15 degrees, 0 degrees, 15 degrees, 45 degrees and sitting positions were compared between groups and for each position. HRV in diabetic patients was lower than in controls at all positions (absolute units). Low-frequency power (normalized units) and the low-frequency/high-frequency ratio increased significantly at 45 degrees and in sitting positions in controls but not in diabetic patients. Pre-existing autonomic derangements in diabetic patients without overt clinical symptoms can be aggravated by high-degree tilting or sitting positions. Consequently, great care should be taken during the intra- and perioperative management of these patients.

The article deals with problems of optimizing sanatorium-and-spa programs to better health in workers exposed to vibration, through using panto-magnesium pearl baths. Examinations covered 49 individuals exposed to local vibration at work, who underwent health programs including magnetotherapy, manual massage and exercise therapy. The authors conclude that maximal effect of improved life quality was seen after panto-magnesium gas baths course auxiliary to the programs.

Context: Repeated hypoglycemia is associated with hypoglycemia-associated autonomic failure (HAAF), a syndrome of defective counterregulation., Objective: HAAF increases the risk of severe hypoglycemia in diabetes, although its mechanism remains unresolved. Because beta-endorphin influences the autonomic response to hypoglycemia via opioid receptor activation, we hypothesized that it is also involved in the pathogenesis of HAAF., Research Design and Methods: We asked whether opioid receptor blockade during antecedent hypoglycemia (60 mg/dl) on d 1 would prevent development of HAAF on d 2 in eight nondiabetic subjects (five males, 3 females; age, 28 +/- 3.5 yr; body mass index, 24.2 +/- 2.1 kg/m(2)). On four occasions, d 1 was: 1) two 90-min hypoglycemic clamps (N-); 2) two 90-min hypoglycemic clamps plus naloxone (N+); 3) two euglycemic 90-min clamps (C); or 4) two euglycemic 90-min clamps plus naloxone (C+)., Results: Day 1 hypoglycemia caused marked deterioration of d 2 hormonal responses to hypoglycemia, consistent with HAAF-i.e. decreased plasma epinephrine, norepinephrine, and glucagon compared to control (C) (374 +/- 71 vs. 810 +/- 94, 307 +/- 65 vs. 686 +/- 98, and 71 +/- 9 vs. 93 +/- 4 pg/ml, respectively, P < 0.01), as well as in endogenous glucose production (24 vs. 163%; P < 0.01). In contrast, naloxone on d 1 completely prevented the defective counterregulatory responses; epinephrine, norepinephrine, and glucagon (852 +/- 82, 769 +/- 77, and 98 +/- 7 pg/ml) and endogenous glucose production recovery (167%) were identical to those after d 1 euglycemia (P < NS for all). Infusion of naloxone alone during euglycemia on d 1 (C+) had no effect on d 2 responses., Conclusions: These data suggest that the opioid signaling system is a promising target for further studies to prevent HAAF.

Background: Obesity has been associated with significant abnormalities of the cardiac autonomic regulation. However, the precise impact of increasing body weight on cardiac autonomic function and the metabolic and hormonal contributors to these changes are presently unclear. The aim of our study was to explore in subjects with increasing values of body mass index (BMI) the alterations of cardiac autonomic function and to establish the potential role of various metabolic and hormonal contributors to these alterations., Materials and Methods: We investigated time and frequency domain heart rate variability (HRV) parameters taken from 24-h Holter recordings, and several anthropometric, metabolic and hormonal parameters (plasma glucose, insulin, triglycerides, free fatty acids, leptin and adiponectin) in 68 normoglycaemic and normotensive women (mean age of 40 +/- 3 years), subdivided according to their BMI into 15 normal body weight (controls), 15 overweight, 18 obese and 20 morbidly obese., Results: Heart rate was increased and HRV was decreased in the morbidly obese group as compared with controls. In overall population, a negative association linked body fat mass (FM) to HRV indices. None of the metabolic and hormonal parameters were significantly related to the HRV indices, after they were adjusted for the body FM., Conclusions: Morbidly obese, normoglycaemic and normotensive young women have increased HR and low HRV, indicating an abnormal cardiac autonomic function and representing a risk factor for adverse cardiovascular events. A decrease of HRV parameters is associated with a progressive increase of body FM. Other metabolic and hormonal factors, characterising obesity, do not show an independent influence on these HRV alterations.

Chemical weapons represent an ever-growing threat, not only for military forces but also for civilian populations. Nerve agents such as those used in terrorist attacks by the Aum sect in Tokyo are among the deadliest of those non conventional weapons. The French military health service has developed a new auto-injector presenting as a self-usable dual-chamber syringe and successfully obtained a new drug approval to provide this new emergency treatment for the military and civilians. After a short review of the pathophysiology and clinical presentation of acute nerve agent, the authors report the development and the process of new drug application. They finally suggest a clinical guideline for practical use in case of terrorist attack.

Intradialytic hypotension (IDH) remains an important cause of morbidity and mortality in chronic hemodialysis (HD) patients and can be ameliorated by cool temperature HD. The baroreflex arc is under autonomic control and is essential in the short-term regulation of blood pressure (BP). This study aimed to investigate if the baroreflex sensitivity (BRS) response to HD differed between standard and cool-temperature dialysate. Ten patients (mean age 67+/-2 years) prone to IDH were recruited into a randomized, crossover study to compare BRS variation at dialysate temperatures of 37 degrees C (HD(37)) and 35 degrees C (HD(35)). Each patient underwent continuous beat-to-beat BP monitoring during a dialysis session of HD(37) and HD(35). During HD(37) 2 patients developed symptomatic IDH, as opposed to 1 with HD(35). However, asymptomatic IDH occurred with a frequency of 0.4 episodes per session with HD(35) and 6.2 episodes per session during HD(37) (odds ratio15.5; 95%CI 5.6-14.2). Although absolute BRS measurements did not differ between the 2 modalities, BRS variability increased during HD(35). Our study has demonstrated that in IDH-prone patients, cool HD resulted in a reduction in heart rate and a greater reduction in cardiac output and stroke volume. Mean arterial pressure was maintained through a significantly greater increase in total peripheral resistance. Furthermore, although absolute BRS values during HD were not significantly altered by a reduction in dialysate temperature, there was a greater percentage increase in BRS values during cool HD. Understanding the varied causes of, and categorizing impaired hemodynamic responses to HD will enable further individualization of HD prescriptions according to patient need.

We examined the efficacy of herpes simplex virus vector-mediated gene transfer of erythropoietin in preventing neuropathy in mouse model of streptozotocin-diabetes. A replication-incompetent herpes simplex virus vector with erythropoietin under the control of the human cytomegalovirus promoter (vector DHEPO) was constructed. DHEPO expressed and released erythropoietin from primary dorsal root ganglion neurons in vitro, and following subcutaneous inoculation in the foot, expressed erythropoietin in dorsal root ganglion neurons in vivo. At 2 weeks after induction of diabetes, subcutaneous inoculation of erythropoietin prevented the reduction in sensory nerve amplitude characteristic of diabetic neuropathy measured 4 weeks later, preserved autonomic function measured by pilocarpine-induced sweating, and prevented the loss of nerve fibres in the skin and reduction of neuropeptide calcitonin gene-related peptide in the dorsal horn of spinal cord of the diabetic mice. We further investigated whether vector-mediated local expression of erythropoietin in dorsal root ganglion neurons can protect in vivo as well as in vitro hyperglycemia-induced axonal degeneration. Our findings show that the AKT/GSK-3beta dependent pathway plays an important role in mediating the protection of erythropoietin against diabetic neuropathy. Herpes simplex virus-mediated transfer of erythropoietin to dorsal root ganglia may prove useful in treatment of diabetic neuropathy.

Induction of hyperadrenergic activity was experimentally achieved in urethane-anesthetized rats using epinephrine (adrenaline). Acute administration of epinephrine (100 microg/kg) for 2 hours induced several cardiac disorders and vasomotor dysfunction. Pretreatment with natural wild honey (5 g/kg) for 1 hour prior to the injection with epinephrine (100 mug/kg) protected the anesthetized normal rats from the incidence of epinephrine-induced cardiac disorders and vasomotor dysfunction. Moreover, posttreatment with natural wild honey (5 g/kg) following the injection with epinephrine (100 microg/kg) for 1 hour showed several ameliorative outcomes to the electrocardiographic parameters and vasomotor dysfunction of anesthetized stressed rats. Furthermore, natural wild honey preserved the positive inotropic effect of epinephrine in both cases. Also, the total antioxidant capacity (AOC) of natural wild honey was found to be very pronounced. Levels of both reduced glutathione and ascorbic acid (vitamin C) were considered relatively high in natural wild honey. Activity of superoxide dismutase (SOD) was also high, whereas catalase activity was relatively low, especially when compared to the value of SOD activity. It would appear from the results of the present study that natural wild honey may exert its cardioprotective and therapeutic effects against epinephrine-induced cardiac disorders and vasomotor dysfunction directly, via its very pronounced total AOC and its great wealth of both enzymatic and nonenzymatic antioxidants involved in cardiovascular defense mechanisms, besides its substantial quantities of mineral elements such as magnesium, sodium, and chlorine, and/or indirectly, via the enhancement of the endothelium-derived relaxing factor nitric oxide release through the influence of ascorbic acid (vitamin C).

Objective: A dysregulation of the autonomic nervous system is discussed as a pathogenetic factor in migraine. As acupuncture has been shown to exhibit considerable autonomic effects, we tested whether the clinical effects of acupuncture in migraine prophylaxis are mediated by changes of the autonomic regulation., Methods: We simultaneously monitored changes of heart-rate variability (HRV) as an index of cardiac autonomic control and clinical improvement during an acupuncture treatment in 30 migraineurs. HRV was derived from spectral analysis of the electrocardiogram, which was performed before, during, and after the first and the last session of a series of 12 acupuncture sessions. Migraineurs were randomly allocated to 2 groups receiving either verum acupuncture (VA) or sham acupuncture (SA) treatment., Results: Across the combined VA and SA groups, the clinical responders (with at least 50% reduction of migraine attacks) exhibited a decrease of the low-frequency (LF) power of HRV in the course of the treatment, which was not be observed in patients without clinical benefit. VA compared with SA induced a stronger decrease of high-frequency power. The mode of acupuncture, however, did not have an impact on the LF component of HRV or the clinical outcome., Discussion: The data indicate, that VA and SA acupuncture might have a beneficial influence on the autonomic nervous system in migraineurs with a reduction of the LF power of HRV related to the clinical effect. This might be due to a reduction of sympathetic nerve activity. VA and SA induce different effects on the high-frequency component of HRV, which seem, however, not to be relevant for the clinical outcome in migraine.

Reasons for Performing Study: There is much evidence to suggest that group III Clostridium botulinum (types C and D) are involved in the aetiology of equine grass sickness (EGS). Antibodies have been detected previously in the blood and high levels associated with resistance to disease. Specific mucosal antibodies in the gastrointestinal (GI) tract are likely to be important in protection, and this study was performed to ascertain if such antibodies could be detected and if their levels were related to disease state., Objectives: To develop a method for quantifying IgA antibodies to C. botulinum types C and D in the GI tract of horses and to relate antibody levels to disease status., Methods: Samples of tissue (n = 25: 6 duodenum, 7 jejunum and 12 ileum) were taken from acute grass sickness (AGS) cases and from control horses (n = 12; 4 samples from each site) at post mortem. They were extracted with the detergent saponin in the presence of protease inhibitors and assayed for total IgA, for specific IgA against botulinum neurotoxins types C and D (BoNT/C or BoNT/D), and against surface antigens of a BoNT/C negative strain of C. botulinum type C (SA) and of Clostridium tetani (TetSA), as a control. Specific IgA was expressed as percentage total IgA., Results: Compared to controls, significantly higher levels of specific IgA against BoNT/C were detected in the jejunum (P = 0.04) and ileum (P = 0.02) of AGS cases. Similarly, higher specific levels against BoNT/D were demonstrated in duodenum (P = 0.01) and jejunum (P = 0.02). Significantly higher levels of IgA against SA were demonstrated only in duodenal samples (P = 0.01)., Conclusions: Levels of IgA antibody to BoNTs in control horses were at near undetectable levels, suggesting no recent exposure to toxins. In AGS cases, significantly higher levels of specific IgA were detected predominantly in jejunum and ileum., Potential Relevance: If specific IgA is protective then any successful vaccine for EGS should induce a mucosal response.

62 patients who had undergone mild craniocerebral injury have taken part in the study. All patients had a complex examination before the treatment. This examination included together with laboratory and instrumental methods the following scales: vegetovascular Vein's scale for a patient and physician, feeling scale (psychological scale). All patients received the following treatment: analgetics, vasoactive agents, tranquilizers, vitamins of the group B, magnesium sulfate, biostimulants, amino acids, physiotherapy, acupuncture, Patients of the first group received additionally noofen and patients of the second group received aminalon. The duration of the treatment was about two months. Positive dynamics of the course of the disease was noted in patients with late closed craniocerebral injury effect after a complex treatment including nootropic agents was done. However noofen was more effective in patients with closed craniocerebral injury late effect who had asthenic syndrome and vegetative disorders.

Autonomic nerve (sympathic and parasympathic) damage plays a crucial role in the aetiology of bladder dysfunction that occurs after resection of deeply infiltrating endometriosis (uterosacral ligaments, colorectal bowel, rectovaginal wall). This review presents an overview of the pathophysiology and management of voiding dysfunction that occur after this kind of surgery. The rate of significant post-voiding residual volume and/or hypoactive bladder after colorectal resection for endometriosis ranges from 15 to 20%. This rate seems to be higher (up to 30%) after proximal utero-sacral ligaments resection. This is explained by the location of the inferior hypogastric plexus at the proximal portion of the utero-sacral ligaments. Urodynamics investigations show non specific hypoactive bladder and altered uroflowmetry. Concerning treatment, further controlled studies are needed to assess the hypothetical usefulness of parasympathomimetic and prokinetic agents for hypoactive bladder occurring after pelvic autonomic denervation. Neuromodulation is a successful treatment for patients with refractory lower urinary tract dysfunction. However, there is no controlled study that focused on its efficacy in voiding dysfunction after radical pelvic surgery. Overall, the main objective of the treatment is to avoid the complications of post-voiding residue (such as infection) and of abdominal pushing effort (deterioration of perineal tissues). Therefore, self catheterization should be recommended when this postoperative complication occurs. An understanding of the location of the autonomic pelvic network should help prevent iatrogenic injury through the adoption of surgical techniques, such as nerve sparing, that reduce postoperative autonomic dysfunction.

Angiotensin II (Ang II)-induced arterial baroreflex dysfunction is associated with superoxide generation in the brain. Exercise training (EX) improves baroreflex function and decreases oxidative stress in cardiovascular diseases linked to elevated central Ang II. The aim of this study was to determine whether previous EX prevents baroreflex impairment caused by central administration of exogenous Ang II via an Ang II-superoxide mechanism. Four groups of rats were used: non-EX artificial cerebrospinal fluid infused, non-EX Ang II infused, EX artificial cerebrospinal fluid infused, and EX Ang II infused. Rats were treadmill trained for 3 to 4 weeks and subjected to intracerebroventricular infusion of Ang II over the last 3 days of EX. Twenty-four hours after the end of EX, the arterial baroreflex was assessed in anesthetized rats. Compared with non-EX artificial cerebrospinal fluid-infused rats, Ang II significantly decreased baroreflex sensitivity (maximum gain: 3.0+/-0.2% of maximum per millimeter of mercury versus 1.6+/-0.1% of maximum per millimeter of mercury; P<0.01), which was abolished by acute intracerebroventricular infusion of the Ang II type 1 receptor antagonist losartan and the reduced nicotinamide-adenine dinucleotide phosphate oxidase inhibitor apocynin. EX prevented the decrease in baroreflex sensitivity and downregulated Ang II type 1 receptor and NADPH oxidase subunit protein expression in the paraventricular nucleus of Ang II-infused rats. Finally, EX decreased superoxide production in the paraventricular nucleus of Ang II-infused rats. These results indicate that EX improves arterial baroreflex function in conditions of high brain Ang II, which is mediated by the central Ang II type 1 receptor and associated with a reduction in central oxidative stress.

The neuropathic complications related to Diabetes may affect the somatic, sympathetic and parasympathetic nervous system. As a result, there are several clinical manifestations of diabetic neuropathy. They can be related to nervous system lesions of the genital, urinary, gastro-intestinal, skin and cardiovascular tissues. The results of these alterations are loss in the quality of life as well as increase of mortality indexes related to sudden death with cardiac arrhythmias and other causes. The cardiovascular autonomic neuropathy probably contributes to the bad prognosis of the coronary heart disease and of the heart failure in type 1 and type 2 diabetic patients. For diabetologists, the nervous complications of diabetes are the result of an increase influx of glucose to the neuronal and endothelial cells. Evidences show that, with the aim of preventing these complications, the diabetic patients should receive a precocious diagnosis and be instructed for having a good metabolic and blood pressure control. Use of angiotensin converting enzyme inhibitors and beta adrenergic blockers are probably of impact in the prevention of the cardiac autonomic complications of diabetes.