Effect of electric and chemical stimulation of the raphe obscurus on phrenic nerve activity in the cat

The effect of electrical and chemical (l-glutamate) stimulation of the raphe obscurus on phrenic nerve activity was examined in the cat. Phrenic nerve activity was recorded from a C5 nerve root in anesthetized, paralyzed and artificially ventilated cats. Neural discharge was quantitated by integrating the phrenic nerve activity. The respiratory frequency was determined from the integrated nerve signal. Focal electrical stimulation (18–144 μA; 5–40 Hz; 100 μs pulse duration) resulted in significant (P < 0.05) increases in both integrated phrenic nerve (IPN) amplitude and respiratory frequency. These changes were dependent upon current intensity and frequency of stimulation. The largest increases in IPN amplitude and respiratory frequency were47 ± 17%and146 ± 8%, respectively. To insure that the changes in integrated phrenic nerve activity (IPNA) were the result of stimulation of cell bodies and not axons of passage,l-glutamate (100, 200 nmol) was microinjected (100 nl) into the raphe obscurus. Significant (P < 0.05) dose-related changes occurred in integrated phrenic nerve amplitude with an increase of44 ± 13% at 100 nmol and80 ± 13% at 200 nmoll-glutamate. No significant increase in respiratory frequency was observed withl-glutamate microinjection. The results suggest that the raphe obscurus may be involved in respiratory control.     

Conjunctival oxygen tension is influenced by plasma and blood volume, and flow through the external carotid artery

An investigation of the feasibility and validity of measurement of the conjunctival oxygen tension as a monitor of peripheral circulation, blood and extracellular fluid volume and cerebral circulation was carried out in 7 healthy volunteers and 5 unconscious critical care patients with proven total cerebral infarction. The healthy volunteers were subjected to changes in hydration achieved by the administration of furosemide and subsequent rehydration by administration of normal saline. Conjunctival oxygen tension was found to be a sensitive indicator of changes in the degree of hydration presumably by its ability to detect changes in peripheral circulation depending upon circulating blood and extracellular fluid volume. A drawback is that other stimuli of the sympatho-adrenergic system such as temperature and pain, interfere with measurement in the conscious volunteer. In patients with presumed total brain infarction the conjunctival PO₂ cannot be used as a reliable monitor of cerebral blood flow because of varying perfusion of the palpebral conjunctiva from the external carotid artery in the occasional patient.     

Short and long term effects of exercise training on the tonic autonomic modulation of heart rate variability after myocardial infarction

We studied the effects of cardiac rehabilitation on the sympathovagalcontrol of heart rate variability in 30 patients after a first,uncomplicated myocardial infarction. Twenty-two patients completed8 weeks of endurance training (trained), while eight decidednot to engage in the rehabilitation programme for logisticalreasons, and were taken as untrained controls. Age, site ofinfarction, ejection fraction, ventricular diameter and stresstest duration were similar in the two groups at baseline. Heartrate variability was evaluated 4 weeks after infarction beforestarting rehabilitation, and repeated 8 weeks and one year laterin both trained and untrained patients. Measures of heart ratevariability, obtained from both time- and frequency- domainanalysis of a 15 min ECG recording in resting conditions, wereas follows: mean RR interval and its standard deviation (RRSD),the mean square successive differences (MSSD), the percent ofRR intervals differing >50 ms from the preceding RR (pNTN50),the low and high frequency components of the autoregressivepower spectrum of the RR intervals and their ratio (LF/HF).At baseline, heart rate variability was similar in trained anduntrained patients. In the short term (8 weeks after infarction),training increased RRSD by 25% (P<0·01), MSSD by 69%(P<0·01), pNN50 by 120% (P<0·01), and reducedLF/HF ratio by 30% (P<0·01). The effects persistedafter one year in trained patients. In untrained patients, theautonomic control of heart rate variability did not change 8weeks after myocardial infarction and was only slightly modifiedby time. Thus, exercise training, performed for 8 weeks aftera myocardial infarction, modifies the sympathovagal controlof heart rate variability toward a persistent increase in parasympathetictone, known to be associated with a better prognosis. This maypartly account for the favourable outcome of patients who undergorehabilitation.     

年龄因素对健康人心率变异性的影响

目的探讨年龄因素对健康人心率变异性（ＨＲＶ）的影响。材料与方法将２３６例健康人分为五个年龄组，使用美国先进医用设备公司５．０版本ＨＲＶ软件做短时时域及频域ＨＲＶ分析。结果年龄因素对健康人ＨＲＶ短时时域和频域分析的多项指标产生显著影响，随着年龄增大，时域指标中的ＨＲＳＤ、ＳＤＡＮＮ、ｒＭＳＳＤ及ＰＮＮ５０均逐渐降低；随着年龄增长，频域指标中各频段下的绝对面积，即：ＶＬＦ、ＬＦ、ＭＦ及ＨＦ均逐渐降低；而频域指标中各频段下的相对面积，即：ＶＬＦＰ、ＬＦＰ、ＭＦＰ、ＨＦＰ随着年龄增长呈不同的发展趋势。ＬＦ／ＨＦ随着年龄的增加而逐渐升高。结论ＨＲＶ随着年龄的增加而下降，尤以迷走神经活性下降为显著。频域指标中各频段的相对面积较绝对面积能更敏感地反映交感、迷走神经张力的消长。     

Interleukin-6 production by astrocytes: Induction by the neurotransmitter norepinephrine

Astrocytes contribute to the immunocompetence of the central nervous system (CNS) via their expression of class II major histocompatibility complex (MHC) antigens and the production of inflammatory cytokines such as interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6). Of these cytokines, IL-6 is of particular interest because one of its many immune and inflammatory actions is the promotion of immunoglobulin synthesis, and it is thought that IL-6 expression within the brain exacerbates autoimmune diseases of the CNS, which are marked by local immunoglobulin production. Several stimuli induce astrocyte IL-6 expression, including such inducible endogenous factors as IL-1β and TNF-α. We have investigated the possibility that a constitutively present endogenous factor, the neurotransmitter norepinephrine (NE), can induce astrocyte IL-6 production. We report that NE induces both IL-6 mRNA and protein in primary neonatal rat astrocytes, with optimal induction at 10 μM. IL-6 protein induction by NE is comparable to that seen with IL-1β or TNF-α, and NE synergizes with these cytokines for a ten-fold enhanced effect. In contrast to astrocytes, microglia are relatively unresponsive to NE, IL-1β and TNF-α for IL-6 production. Experiments with the β-adrenergic receptor agonist isoproterenol, and α and β-adrenergic receptor antagonists (propranolol, phentolamine, atenolol, and yohimbine) indicate that β₂ and α₁-adrenergic receptors are involved in NE induction of astrocyte IL-6 expression. These results help to further the understanding of neuron-glial interactions, and the role of astrocytes and adrenergic activity in immune responses within the CNS.     

γ-Enolase and glial fibrillary acidic protein in nervous system tumors

Summary A large series of central and peripheral nervous system tumors was studied for the presence of glial fibrillary acidic protein (GFAP) and -enolase (neuron-specific enolase, NSE), using specific monoclonal antibodies (mAbs). Occurrence in and specificity of GFAP to glial and mixed tumors was confirmed and depended on the malignancy grade and features such as meningeal invasion. Using a well-characterized mAb, -enolase was demonstrated in neuronal, as well as in a whole range of non-neuronal tumors. This lack of specificity of -enolase prohibits its use as an exclusive neuronal marker. Nevertheless quantization or comparison with other types of enolases could still prove to be useful in well-defined situations. The advantages inherent to mAbs and a highly sensitive detection system turn GFAP stainings into a specific and readily reproducible technique.Supported in part by FGWO (grant no. 3.0019.86) and by the Geconcerteerde Actie (grant no. 84/89-68, Brain specific proteins)     

Cardiovascular reflexes and low long-term exposure to mercury vapour

Summary Subjective symptoms related to autonomic dysfunction and quantitative non invasive tests measuring both sympathetic and parasympathetic functions of the autonomic nervous system were studied among a group of 41 chlorine-alkali workers with low long-term exposure to mercury (Hg') vapour and their matched referents. The test battery included measurements of pulse rate variation in normal and deep breathing, in the Valsalva manoeuvre and in vertical tilt as well as blood pressure responses during standing and isometric work. The exposure time had been 16 years on average, and the mean exposure to Hg vapour was estimated to have been about 30 g/m³ of air. Only a tendency for a subtle reduction of cardiovascular reflex responses and a slight increase of subjective symptoms were seen in the exposed group, but no significant autonomic dysfunction was associated with the low level of exposure.     

The unit impulse response procedure for the pharmacokinetic evaluation of drug entry into the central nervous system

The unit impulse response theory has been adapted to characterize the transport profile of drugs into the central nervous system (CNS). From the obtained input function, the cumulative plasma volume (V) cleared by transport into the CNS in time can be calculated. Simulation studies demonstrated that transport governed by passive diffusion resulted in a linear relationship between V and time, while the slope of the line, the blood- brain barrier (BBB) clearance, proved to be an adequate and model independent parameter to characterize drug transport into the CNS. The error in the result of the numerical procedure could be limited to less than 10% of the theoretically predicted value. Superposition of 5 or 10% random noise on simulated data did not result in significant differences between the calculated and theoretically predicted clearance values. Simulations of carrier-mediated transport resulted in nonlinear transport curves; the degree of nonlinearity, and thus the detectability, was dependent on the initial degree of saturation of the system, the rate of desaturation, as caused by drug elimination processes and the noise level on the data. In vivoexperiments in the rat were performed, using atenolol, acetaminophen, and antipyrine as model drugs. Linear transport relationships were obtained for all drugs, indicating that transport was dependent on passive diffusion or a low affinity carrier system. BBB- clearance values were 7±1 l/min for atenolol, 63±7 ul/min for acetaminiphen and 316±25 l/min for antipyrine. These experiments validate the applicability of the presented technique in in vivostudies.     

Genetic screen for mutations affecting development and function of the enteric nervous system.

An intact enteric nervous system is required for normal gastrointestinal tract function. Several human conditions result from decreased innervation by enteric neurons; however, the genetic basis of enteric nervous system development and function is incompletely understood. In an effort to increase our understanding of the mechanisms underlying enteric nervous system development, we screened mutagenized zebrafish for changes in the number or distribution of enteric neurons. We also established a motility assay and rescreened mutants to learn whether enteric neuron number is correlated with gastrointestinal motility in zebrafish. We describe mutations isolated in our screen that affect enteric neurons specifically, as well as mutations that affect other neural crest derivatives or have pleiotropic effects. We show a correlation between the severity of enteric neuron loss and gastrointestinal motility defects. This screen provides biological tools that serve as the basis for future mechanistic studies.     

Characterization of the antisecretory action of prostaglandin D2 in the rat colon

Previous studies have shown that prostaglandin D₂ (PGD₂) inhibits neuronally mediated secretion in the rat colon. This antisecretory action of PGD₂ was further characterized by the use of a prostaglandin D receptor blocker. Prostaglandin D₂ inhibited the neuronally mediated short-circuit current evoked by prostaglandin I₂, which represents Cl^- secretion. The concentration-response curve for the inhibition by PGD₂ was shifted to the right in the presence of the prostaglandin D receptor blocker, AH 6809. AH 6809 had no effect on the short-circuit current response induced by prostaglandin E₂ or iloprost, a stable prostaglandin I₂ analogue, suggesting an interaction of the blocker with receptors specific for PGD₂. A direct interaction of PGD₂ with enteric neurones was studied by determining its effect on acetylcholine release from enteric neurones preloaded with [³H]choline. Prostaglandin D₂ suppressed ³H release induced by electric field stimulation. It had, however, no effect on the release induced by depolarization with potassium. The results suggest that the inhibitory action of PGD₂ on enteric cholinergic neurones is mediated by prostaglandin D receptors.