Inter-ictal assay of peripheral circulating inflammatory mediators in migraine patients under adjunctive cervical non-invasive vagus nerve stimulation (nVNS): A proof-of-concept study

Objective

To assay peripheral inter-ictal cytokine serum levels and possible relations with non-invasive vagus nerve stimulation (nVNS) responsiveness in migraineurs.

Host–microbiome interactions: the aryl hydrocarbon receptor as a critical node in tryptophan metabolites to brain signaling

ABSTRACT

Tryptophan (Trp) is not only a nutrient enhancer but also has systemic effects. Trp metabolites signaling through the well-known aryl hydrocarbon receptor (AhR) constitute the interface of microbiome-gut-brain axis. However, the pathway through which Trp metabolites affect central nervous system (CNS) function have not been fully elucidated. AhR participates in a broad variety of physiological and pathological processes that also highly relevant to intestinal homeostasis and CNS diseases. Via the AhR-dependent mechanism, Trp metabolites connect bidirectional signaling between the gut microbiome and the brain, mediated via immune, metabolic, and neural (vagal) signaling mechanisms, with downstream effects on behavior and CNS function. These findings shed light on the complex Trp regulation of microbiome-gut-brain axis and add another facet to our understanding that dietary Trp is expected to be a promising noninvasive approach for alleviating systemic diseases.     

AN UNUSUAL BILATERAL VAGAL PARAGANGLIOMAS： ONE CASE STUDY

VAGAL paraganglioma VP)is an uncommonneoplasm originating from neural crest paragan-glion cells located along the vagus nerve,repre-senting less than5%of all paragangliomas of the head andneck.1Despite improvement in microsurgical techniques,management of…     

The difference in blood pressure between upper arm and finger during physical exercise

Summary. A new apparatus which measures the blood pressure in the finger continuously and yet not invasively was tested for its usefulness during exercise. It was compared with upper arm measurements in 23 volunteers during prolonged bicycle ergometry. Simultaneously, a pulse plethysmogram was recorded from another finger of the same arm, whereas in six additional volunteers Doppler measurements were carried out on the radial artery. The results show that finger systolic pressure ceased to rise at about 40% of maximal exercise; the difference with the continuously rising systolic pressure in the upper arm becoming significant at 140 W. At the same time the amplitude of the finger plethysmogram became significantly higher than its initial value, indicating distinct cutaneous vasodilation, whereas the volunteers also became hot and started to perspire. However, the radial artery ‘flow’, deduced from the Doppler measurements, did not change significantly during exercise. It increased sharply and markedly in the cooling down period. Simultaneously with this increase in flow, HR and both systolic blood pressures fell drastically whereas the plethysmography amplitude remained about stable at its raised level. The results fit in with the idea that a compromise is achieved between the need for muscle activity and the need for temperature regulation. It is concluded that the Finapres functions well during exercise, but that the systolic pressure in the finger is not representative for its more central counterpart during cutaneous vasodilation. It is argued that opening up of AVAs may contribute to this pressure effect.     

Monolateral hypoplasia of the motor vagal nuclei in a case of sudden infant death syndrome

During the development of motor vagal nuclei (MVN), the neuroblasts of the myeloencephalic basal plate migrate in the dorsolateral direction to form the dorsal motor vagal nucleus (DMVN) and ventrolaterally to form the ventral motor vagal nucleus (VMVN). Those neuroblasts that remain close to the median sulcus will form the hypoglossal nucleus. In support of the congenital origin of the alteration of the MVN in sudden infant death syndrome (SIDS), we report the case of an 8‐month‐old female child who was found dead in her cot. The neuropathological assessment revealed that the medullary triangle of the 4th ventricle floor was asymmetric, owing to the presence of three prominences to the left side of the median sulcus. The medial prominence corresponded to the hypoglossal nucleus, which showed a marked increase in the number of large neurons; the intermediate prominence corresponded to the DMVN whose large neurons were reduced and were recognizable mainly at the level of the medial fringe; the lateral prominence corresponded to the solitary nucleus. The left solitary tract showed a reduction of the transverse diameter. Also, the left VMVN showed marked reduction in the number of neurons. Inflammatory and astrocytic reactions were absent. We suggest that in SIDS cases the hypocellularity of the MVN and the increased number of neurons of the hypoglossal nucleus are intimately related, indicating a congenital alteration due to incomplete migration of the vagal neuroblasts with abnormality of the autonomic cardio‐respiratory control.     

Pharmacology of the internal anal sphincter and its relevance to faecal incontinence

1 The internal anal sphincter (IAS) has a spontaneous tone and is the main contributor to the maintenance of faecal continence. The spontaneous resting tone exhibited by the sphincter can be modified by neurotransmitters from the autonomic and enteric nervous systems. 2 In this review, the influence of the sympathetic and parasympathetic nervous systems on IAS tone are discussed and the putative roles of nitric oxide, carbon monoxide, vasoactive intestinal peptide and adenosine triphosphate in non‐adrenergic non‐cholinergic transmission are considered. 3 Faecal incontinence is a common condition that places a heavy financial burden on the health service and severely affects patients’ quality of life. Resting anal pressure is reduced in patients with faecal incontinence and agents that increase sphincter tone tend to relieve symptoms. The results of clinical studies of the use of phenylephrine to treat faecal incontinence are reviewed. 4 It is concluded that the IAS is a potential target for drug development for the treatment of faecal incontinence.     

Haemodynamics as a determinant of the pharmacokinetics of and the plasma catecholamine responses to isoprenaline

Summary The total body clearance and fractional extraction of isoprenaline (ISO) have been determined, and the relation between these parameters and cardiac output established. Whether desipramine, an inhibitor of neuronal uptake, altered the plasma catecholamine response to ISO was also investigated.Seven healthy subjects were given i.v., infusions of ISO in two, consecutive 25-min periods, at constant dose rates of 31–43 and 80–124 pmol·kg^–1·min^–1, respectively. The total-body (ER), pulmonary (ER_p) and forearm (ER_f) fractional extractions and the total body clearance (CL) of ISO were obtained from measurements of cardiac output and the steady-state ISO concentration in mixed central venous, arterial and forearm venous plasma.ISO-induced increases in cardiac output resulted in increases in CL, decreases in ER and no consistent change in ER_f. ER_p did not differ from zero. ISO also produced a dose-dependent increase in the mixed venous plasma concentrations of noradrenaline and 3,4-dihydroxyphenylglycol (DOPEG), and a decrease in that of adrenaline. Pretreatment with desipramine did not alter any of the pharmacokinetic parameters of ISO. Desipramine, however, reduced the mixed venous baseline plasma levels of noradrenaline (47%) and DOPEG (40%), and tended to reduce that of adrenaline (34%). It enhanced the plasma noradrenaline response 2.4-fold, abolished the plasma DOPEG response and did not alter the plasma adrenaline response to ISO.Hence, owing to its haemodynamic effects, ISO modifies its own pharmacokinetics which involve non-neuronal removal processes only. The increased DOPEG in plasma resulting from the ISO-induced increase in noradrenaline release was presynaptic in origin. Desipramine appears to reduce sympathetic activity. The enhancement by desipramine of the ISO-induced increase in plasma noradrenaline points towards recapture by neuronal uptake of at least 58% of the noradrenaline released in response to ISO.     

Heart rate response to breathing: dependency upon breathing pattern

Summary. Heart rate responses to stepwise and periodic changes in lung volume were studied in seven young healthy males. Stepwise inspiration and expiration both resulted in an increase in heart rate followed by a rapid decrease in heart rate. The fastest heart rate was reached in 1·6 ± 0·5 s and in 3·6 ± 1·4 s in response to inspiration and expiration, respectively (P < 0·01). The slowest heart rate was reached in 4·8± 1·0 s and in 7·6± 1·9 s in response to inspiration and expiration, respectively (P < 0·01). Following this biphasic change the heart rate returned to a steady level. The difference between the fastest and the slowest heart rates was significantly larger in response to inspiration (21·7 ± 7·3 beats per minute) than in response to expiration (12·0±7·3 beats per minute; P < 0·01). Periodic changes in lung volume were performed with frequencies from 3·0 to 12·0 respirations per minute (r.p.m.). The changes in heart rate showed a constant amplitude in the frequency range below 5·5 r.p.m. Maximal heart rate changes were found at frequencies of 5·5 to 7·0 r.p.m. Changes in heart rate decreased in a linear manner on a log-log scale in the frequency range above 7·0 r.p.m. The relation between frequency and changes in heart rate is explained by interference between the transient changes in heart rate induced both by inspiration and by expiration. It is concluded that if heart rate changes in response to periodic changes in lung volume are to be used as a measure of vagal function a number of factors have to be taken into consideration and to simplify the analysis of heart rate responses to breathing we recommend, instead, the use of the transient changes in heart rate induced by stepwise changes in lung volume.     

Effects of low-dose transdermal scopolamine on autonomic cardiovascular control in healthy young subjects

We studied how posture influences the effects of transdermal scopolamine on autonomic cardiovascular regulation in a randomized, double-blind, placebo-controlled crossover study of 10 healthy young volunteers. We recorded the electrocardiogram and auscultatory sphygmomanometric and continuous non-invasive finger arterial pressure (Finapres device) to obtain signals for the beat-by-beat R–R interval and systolic, mean and diastolic pressures. R–R interval and arterial pressure variabilities were characterized by power spectral analysis. Scopolamine increased the mean R–R intervals and reduced arterial pressure in both the supine and the standing positions, but did not affect blood pressure variability. Scopolamine increased the total variability of R–R interval and its mid- (0·07–0·15 Hz) and high- (0·15–0·40 Hz) frequency band power in the standing position during controlled breathing at 0·25 Hz. In the supine position, scopolamine did not affect R–R interval variability. In the deep breathing test, scopolamine increased the maximal expiratory–inspiratory R–R interval ratio. This study showed that low-dose scopolamine increases vagal cardiac inhibition in both supine and standing positions in healthy volunteers. However, scopolamine increases heart rate variability only in the standing position during partial vagal withdrawal. The study also demonstrates that transdermal scopolamine decreases blood pressure in healthy young subjects.