Breathing of awake goats during prolonged dysfunction of caudal M ventrolateral medullary neurons

Recent scientific studies have demonstrated the efficacy of various forms of immunotherapy for the treatment of allergic diseases. Traditional subcutaneous immunotherapy, sublingual, oral, and intranasal immunotherapy have been shown to significantly reduce symptoms and favorably modulate the immune response. Outcome studies that use patient response data from standardized surveys represent the next challenge to all practicing allergists.     

Effects of ACh on the electric activity of rostral ventrolateral medullary neurons of rat in vitro

Extracellular single-unit discharges were obtained from 165 spontaneously active neurons within the region of the rostral ventrolateral medulla (RVLM) by glass microelectrode from 89 brain slices of the Sprague-Dawley rats. The units could be divided into three types: regular (61.8%), irregular (24.2%) and silent (14%). Acetylcholine (ACh, 0.1, 0.3 mumol/L) showed four kinds of effects on spontaneous discharges of RVLM neurons: excitatory, inhibitory, biphasic and non-responsive, counting respectively 41.8%, 20%, 3% and 35.2% of the neurons tested. The excitatory effect of ACh was dose-dependent. The effects, either excitatory or inhibitory, of ACh (n = 49) were mostly blocked by atropine (0.3 mumol/L, n = 42). The excitatory effect of ACh (n = 14) could be blocked mainly by selective antagonist of M1 receptor, pirenzepine (PZ, 30 nmol/L, n = 9), but not by selective antagonist of M2 receptor, methoctramine (MT) and AFDX-116. The inhibitory effect of ACh (n = 10) could be blocked mostly by M2 receptor antagonist MT (30 nmol/L, n = 7); and this inhibitory effect (n = 9) could be blocked mostly by another M2 receptor antagonist AFDX-116 (30 nmol/L, n = 6), but not by M1 receptor antagonist PZ.     

Changes in the impulse activity of neurons of the human thalamic ventrolateral nucleus during voluntary movement

Functional differences were revealed in evoked activity of two types (A and B) of units of the human thalamic ventro-lateral nucleus (VL). Collective activities of these polyfunctional neurons were selectively related to triggering and execution phases of movement. Common character of dynamics of the responses seems to be due to similar polyfunctional nature as well as to the functional role of these two complementary elements in the motor signal transmission. The collective activities reflect in the VL the integrative processes related to processing and programming of generalised parameters of motor signals, but unrelated to performance of a concrete motor act.     

Patch-clamp recordings of membrane currents evoked during natural synaptic activity in sympathetic neurons

BACKGROUND: Cationic streptococcal proteinase (erythrotoxin B) and its precursor, zymogen, are putative nephritogenic antigens. The present study was designed to test whether serum titers to these antigens were good markers of streptococcal infection associated with glomerulonephritis. METHODS: We studied 153 patients (male/female = 104/49, age range, 2 to 23 years old) with acute poststreptococcal glomerulonephritis (APSGN) from three countries (Venezuela, Chile and Argentina). The site of the initial infection was the skin in 84 patients, the throat in 55 patients and was unknown in 14 patients. In addition, we studied 23 patients (1 to 24 years old) with streptococcal infection not associated with glomerulonephritis (14 patients with impetigo and 9 patients with pharyngitis). As control group, 93 healthy individuals (54 males, 2 to 19 years old) were studied. Anti-zymogen and anti-proteinase titers were determined in a single laboratory by ELISA, and the intra- and interassay coefficients of variation were 5.3% and 8.5%, respectively. ASO titers and anti-DNAse B titers were also done. RESULTS: Anti-zymogen titers of 1:800 to 1:3200 had likelihood ratios (sensitivity/1-specificity) for detection of streptococcal infection in APSGN patients ranging from 2.00 to 44.2 in Argentina, Chile and Venezuela. Anti-zymogen titers decreased one to two months after APSGN and they were 1 to 3 log2 dilutions higher that anti-proteinase titers. Receiver operating characteristic (ROC) curves showed that anti-zymogen titers were consistently superior to anti-streptolysin O and anti-DNAse B titers as markers for streptococcal infection in APSGN. CONCLUSIONS: These results suggest that increased anti-zymogen antibody titers are the best available marker for streptococcal infection associated with acute glomerulonephritis.     

Activation of NMDA and non-NMDA receptors in the caudal ventrolateral medulla dilates the airways

Calpain is a ubiquitous calcium-dependent cysteine protease, whose cytoskeletal protein substrates suggest that it may be important in neuronal differentiation. Lead (Pb2+) is known to substitute for Ca2+ in a variety of intracellular processes, and interferes with the development of hippocampal neurons in vitro. We found that free Pb2+ at 1 nM does not activate calpain in the absence of Ca2+. Pb2+ inhibited the activity of calpain; the degree of calpain inhibition was dependent on an interaction between concentrations of both Ca2+ and Pb2+. In the presence of 1 microM free Ca2+, 10 pM free Pb2+ reduced calpain activity, but in the presence of 100 microM free Ca2+, 1 nM free Pb2+ failed to inhibit calpain. This provides evidence that Pb2+ competes for the Ca2+ binding sites on calpain. In the presence of 40 microM free Ca2+, 1 nM free Pb2+ significantly reduces Vmax without altering Km, suggesting that Pb2+ acts as a noncompetitive inhibitor of calpain. Inhibition of calpain is one mechanism by which Pb2+ may interfere with neuronal development.     

Cardiopulmonary sympathetic input excites primate cuneothalamic neurons: comparison with spinothalamic tract neurons

Stimulation of cardiopulmonary sympathetic afferent fibers excites thoracic and cervical spinothalamic tract (STT) cells that respond primarily to noxious somatic stimuli. Neurons in dorsal column nuclei respond primarily to innocuous somatic inputs, but noxious stimulation of pelvic viscera activates gracile neurons. The purpose of this study was to compare effects of thoracic visceral input on cuneothalamic and STT neurons. Stellate ganglia of 17 anesthetized monkeys (Macaca fascicularis) were stimulated electrically to activate cardiopulmonary sympathetic afferent fibers. Somatic receptive fields were manipulated with brush, tap, and pinch stimuli. Extracellular discharge rate was recorded for neurons antidromically activated from ventroposterolateral (VPL) thalamus. Stimulation of the ipsilateral stellate ganglion increased activity of 17 of 38 cuneothalamic neurons and of 1 gracilothalamic neuron with an upper body somatic field. Spinal cord transections showed that cardiopulmonary input to cuneothalamic neurons traveled in ipsilateral dorsal column and probably in dorsolateral funiculus. One of eight gracilothalamic neurons with lower body fields was inhibited by cardiopulmonary input, and none were excited. Stimulation of the ipsilateral stellate ganglion increased activity in 10 of 10 T3-T4 STT neurons. Evoked discharge rates, latencies to activation and durations of peristimulus histogram peaks were significantly less for cuneothalamic neurons compared with STT neurons. Furthermore, additional long latency peaks of activity developed in histograms for 6 of 10 STT neurons but never for cuneothalamic neurons. Contralateral cardiopulmonary sympathetic input did not excite cuneothalamic neurons but increased activity of 7 of 10 T3-T4 STT neurons. Most cuneothalamic neurons (24 of 31 cells tested) responded primarily to innocuous somatic stimuli, whereas STT neurons responded primarily or solely to noxious pinch of somatic fields. Neurons that responded to cardiopulmonary input most often had somatic fields located on proximal arm and chest. Results of this study showed that cardiopulmonary input was transmitted in dorsal pathways to cuneate nucleus and then to VPL thalamus and confirmed that STT neurons transmit nociceptive cardiopulmonary input to VPL thalamus. Differences in neuronal responses to noxious stimulation of cardiopulmonary sympathetic afferent fibers suggest that dorsal and ventrolateral pathways to VPL thalamus play different roles in the transmission and integration of nociceptive cardiac information.     

Activation of ventrolateral preoptic neurons by the somnogen prostaglandin D2

Prostaglandin D2 (PGD2) is an extensively studied sleep-promoting substance, but the neuroanatomical basis of PGD2-induced sleep is only partially understood. To determine potential regions involved in this response, we used Fos immunohistochemistry to identify neurons activated by infusion of PGD2 into the subarachnoid space below the rostral basal forebrain. PGD2 increased nonrapid eye movement sleep and induced striking expression of Fos in the ventrolateral preoptic area (VLPO), a cluster of neurons that may promote sleep by inhibiting the tuberomammillary nucleus, the source of the ascending histaminergic arousal system. Fos expression in the VLPO was positively correlated with the preceding amount of sleep and negatively correlated with Fos expression in the tuberomammillary nucleus. PGD2 also increased Fos immunoreactivity in the basal leptomeninges and several regions implicated in autonomic regulation. These observations suggest that PGD2 may induce sleep via leptomeningeal PGD2 receptors with subsequent activation of the VLPO.     

Effects of microinjection of L-NNA and SNP into ventrolateral medulla on blood pressure, heart rate and renal sympathetic nerve activity in rats

The effects of microinjection of a NO synthase inhibitor--N-nitro-L-arginine (L-NNA) and NO donor-sodium nitroprusside (SNP) into ventrolateral medulla on blood pressure (BP), heart rate (HR) and renal sympathetic nerve activity (RSNA) were examined in anesthetized rats to define the role of L-arginine: NO pathway in the central regulation of BP and to explore the underlying mechanism. The results obtained were as follows: (1) Following microinjection of L-NNA into rostral ventrolateral medulla (RVLM), both of MAP and RSNA were increased. The effects lasted for more than 30 min and could be reversed by prior intravenous injection of L-arginine. (2) In response to microinjection of SNP into RVLM, MAP and RSNA were decreased, while HR showed no significant change. (3) During microinjection of L-NNA into caudal ventrolateral medulla (CVLM), MAP, HR and RSNA were decreased. (4) Upon injection of SNP into CVLM, MAP and RSNA were increased, but HR showed no significant change. The above-mentioned results indicate that the L-arginine: NO pathway may exhibit a modulatory action on the activity of ventrolateral medulla neurons.     

Tooth pulp neurons in the caudal medulla oblongata of the cat

The medulla oblongata caudal to the obex was explored for neurons responsive to tooth pulp (TP) stimulation in cats. Four different subclasses of TP neurons were found. The latter included TP specific (TPS) neurons, trigeminal wide dynamic range (trigeminal WDR) neurons with TP input, trigeminal subnucleus reticularis ventralis (trigeminal SRV) neurons with TP input and convergent reticular formation (convergent RF) neurons with TP input. TPS neurons were located in the dorsal marginal rim of the trigeminal subnucleus caudalis, i.e., in the marginal layer or the outer zone of substantia gelatinosa. WDR neurons with TP input were found in the neck region of medullary dorsal horn which corresponds to the lateral part of subnucleus reticularis dorsalis (SRD). Trigeminal SRV neurons with TP input were located in the lateral part of SRV. Convergent RF neurons with TP input were found in the middle third of the caudal bulbar RF consisting of SRD and SRV. Both TPS neurons and WDR neurons with TP input included trigeminothalamic neurons as evidenced by the antidromic activation from the nucleus ventralis posteromedialis of the contralateral thalamus. A significant proportion of both trigeminal SRV and convergent RF neurons with TP input were antidromically activated by stimulation of the nucleus centralis lateralis of the contralateral thalamus. The former two subclasses may subserve the sensory-discriminative aspect of toothache, while the latter two subclasses, the emotional-motivational aspect.     

Regulation of galanin in rat sympathetic neurons in vitro

The neuropeptide galanin is induced in sensory and autonomic neurons after peripheral nerve lesion. Leukemia inhibitory factor (LIF) has been suggested to be involved in the up-regulation of galanin. A direct effect of LIF on galanin content in pure sympathetic neuron cultures dissociated from newborn rat superior cervical ganglia was investigated by radioimmunoassay and immunohistochemistry. Galanin increases in sympathetic neurons during a 12 day culture period in the presence of NGF (10 ng/ml). Five days after addition of LIF (10 ng/ml) a 7-fold elevation is observed when compared to control cultures. Furthermore, galanin increases significantly in the presence of non-neuronal cells and in response to potassium-induced depolarization. The proportion of galanin-immunoreactive neurons in mixed cultures is similar to that found in adult rat superior cervical ganglia after transection of the major postganglionic branches. The results corroborate the hypothesis that LIF, presumably released from ganglionic satellite cells, induces galanin in a subpopulation of sympathetic neurons in vivo and in vitro.     

Histochemical localization of adenylate cyclase in cultured sympathetic neurons

The influence of female odors on agonistic behavior among grouped male prairie voles (Microtus ochrogaster) was studied. After the introduction of female odors, investigative behavioral interactions between the males increased in frequency. The source of the odor, the sexual experience of the males, and the ongoing behavior of the group influenced the intensity of the behavioral response. Sexually experienced males showed the greatest number of agonistic instances and attempted sexual interactions after the introduction of urine from estrous females. Agonistic interactions did not decrease upon the introduction of female odors, as has been reported for Mus musculus. It is concluded that these behavioral changes are not due to a response to a releaser pheromone, but are the result of confusion in communication between males.     

The rhythmicity of sympathetic nerve activity

This review focuses on that most engaging feature of the sympathetic nervous system, its rhythmicity. In particular examining the nature of sympathetic nerve activity (SNA), its characteristics, the frequencies of these rhythms and possible mechanisms responsible for their generation. Sympathetic activity can be thought of as a complex output of the central nervous system providing subtle control over end organ function. This control is exerted in a number of frequency bands including rhythms related to the cardiac and respiratory cycles, 10 Hz, and between 0.2 and 0.4 Hz. The generation and control over the occurrence of each of these rhythms is likely to be quite separate. Although afferent feedback from sources such as baroreceptors can explain some of the rhythmical properties in each case there is good evidence for inherent generation of aspects of these rhythms. A variety of brainstem cell groups are thought to be involved in their generation with the rostral ventrolateral medulla, although unlikely to be solely responsible for tone generation, an important regulator of overall activity. SNA also varies in the number of nerves recruited to fire in each synchronized discharge. Little is known about this control other than it appears to be quite separate from the control over the timing of discharges. Spinal cord mechanisms are possibly involved. SNA frequencies above 0.7 Hz do not appear to directly induce oscillations in innervated vasculature, however, are likely to contribute to setting the level of vasconstrictive tone. Slower frequencies appear to directly cause oscillations in blood flow.     

Classification of neurons of the cat neocortex

Different forms of neurons of the temporal cortex of the adult cat were studied in frontal and sagittal sections by the Golgi method in the author's modification. It was shown that the 2nd type Golgi cells (spider neurons, basket cells, spindle stellate cells with two bunches of processes, stellate cells with radial processes, Martinotti's cells) are characterized by local restruction of their processes and differ from one another in the specificity of axonal aborizations. The comparison of axonal systems of the pyramidal and above forms of the 2nd type Golgi cells has shown the set of collaterals of one pyramidal cell to consist of fragments of axonal branching of different forms of short-axon neurons. On the basis of the data obtained the pyramidal neuron is considered as a universal type of cell. The structural features of its receptive surface sustain the converging on it of a wide range of polymodal signals, the difference in the quality of presynaptic structures being responsible for the plasticity of a functional change of its integrative activity.     

The characteristics of the spontaneous activity of single neurons in the human ventrolateral thalamus during changes in the functional state of the brain

In the thalamic ventro-lateral nucleus of parkinsonian patients, two main types of convergent cells were shown to exist: 1) units with irregular discharges (A-cells, 74%) and 2) units with bursts of unstable rhythmic discharges (B-cells, 26%). The functional brain changes were accompanied by modifications of A-cells activity into the transient rhythmic burst-like pattern, characterized by two different types of intrinsic structure burst discharges being in some cases similar to the structure of B-cells. A correlation between activities of these units and the type of parkinsonian pathology was revealed.     

Respiratory quotient is inversely associated with muscle sympathetic nerve activity

The relative amounts of the macronutrients oxidized by an individual are reflected in the respiratory quotient (RQ), which varies inversely with lipid oxidation. A high RQ, indicating a relatively low lipid oxidation, and a low activity of the sympathetic nervous system have both been identified as risk factors for body weight gain. The stimulatory effect of norepinephrine on lipid oxidation suggests that low lipid oxidation may contribute to the relationship between low sympathetic nervous activity and body weight gain. The purpose of the present study was to determine whether low basal muscle sympathetic nerve activity (MSNA), a direct measure of sympathetic nervous outflow, is independently associated with low lipid oxidation. Intraneural recordings of basal MSNA were performed in 39 healthy, nondiabetic males, 19 Caucasians (mean +/-SD, 33 +/- 9 yr, 91 +/- 23 kg, and 28 +/- 11% body fat) and 20 Pima Indians (30 +/- 5 yr, 94 +/- 25 kg, and 35 +/- 8% fat) immediately after measurement of 24-h RQ in a respiratory chamber. Basal MSNA, energy balance, and age were independent determinants of 24-h RQ, together explaining 45% of its variability. Accordingly, 24-h RQ adjusted for energy balance and age was inversely related to MSNA (r = -0.41; P = 0.01). Race, percent body fat, and fasting plasma insulin were not independent determinants of 24-h RQ. Although MSNA explained only a limited part of the variability in 24-h RQ, the results support the hypothesis that an effect on lipid oxidation contributes to the demonstrated relationship between low activity of the sympathetic nervous system and body weight gain.     

Effects of nitric oxide in cultured prevertebral sympathetic ganglion neurons

The effects of the nitric oxide donor, S-nitrosoacetylpenicillamine (SNAP), were tested on cultured dissociated guinea pig celiac ganglion neurons using whole cell patch-clamp recordings. S-nitrosoacetylpenicillamine induced a concentration- and voltage-dependent inwardly directed shift in holding current (inward current shift) in 89% of neurons. The inward current shift was prevented by pre-treatment with the nitric oxide scavenger reduced hemoglobin and was abolished by intra- or extracellular cesium. The amplitude of the inward current shift was also sensitive to the extracellular potassium concentration. The S-nitrosoacetylpenicillamine-induced inward current shift was mediated by a decrease in calcium-dependent potassium currents (IAHPs); apamin (100 nM), charybdotoxin (10 nM) or tetraethylammonium (5 mM) reduced but did not abolish the amplitude of its inward current shift and a combination of apamin and tetraethylammonium abolished the S-nitrosoacetylpenicillamine-induced inward current response. In the presence of extracellular cobalt, SNAP produced an outward current that was concentration- and voltage-dependent, abolished by reduced hemoglobin and extracellular cesium and reduced by 4-AP (1 mM); in the absence of cobalt, 4-AP increased the SNAP-induced inward current shift. These data indicate that NO exerts dual opposing effects on neuronal potassium conductances, namely an inward current shift mediated through an inhibition of IAHP and induction of an outward current mediated by activation of the potassium delayed rectifier.     

Fos expression in rat pontine tegmental neurons following activation of the medial preoptic area

Because murine myeloma plasma cells and normal human lymph node plasma cells express BCL-X, we evaluated BCL-X expression in malignant human plasma cells. BCL-X expression was detected in several human myeloma cell lines, as well as in CD38-sorted bone marrow cells obtained from some patients. Only the antiapoptotic long form of BCL-X (BCL-X-L), was detected. Because BCL-X-L expression can protect tumor cells from apoptotic death induced by chemotherapeutic agents, we tested the clinical relevance of expression in 55 archival bone marrow biopsies. The biopsies were stained by immunohistochemistry, and BCL-X expression was correlated with the subsequent response to treatment. BCL-X expression in malignant plasma cells strongly correlated with decreased response rates in patient groups treated with either melphalan and prednisone or vincristine, Adriamycin, and dexamethasone. Response rates were 83-87% in non-BCL-X-expressing cases and 20-31% in BCL-X-expressing cases. In addition, BCL-X expression was more frequent in specimens taken from patients at relapse (77%), when compared to those at initial diagnosis (29%). Further support for the association of drug resistance with BCL-X-L expression came from studies of the 8226 dox-40 cell line. This line, which expresses p-glycoprotein and serves as a model of multidrug resistance in multiple myeloma cells, demonstrated an up-regulated expression of BCL-X-L, which was relatively specific, in that BCL-2 or BAX expression was not altered. In addition, dox-40 cells demonstrated a generalized resistance to apoptosis that was induced by several different agents. These results indicate that malignant plasma cells can express BCL-X-L and that such expression may be a marker of chemoresistant disease.     

Electrophysiological properties and cholinergic responses of rat ventral oral pontine reticular neurons in vitro

This study analyses the relationship between the use of rotating instruments, the production of a smear layer and the presence of alterations to enamel microstructures. The rotating instruments used were carbide (8-12 blade) and diamond tipped (30-15 m) cutters. Cavities were made in extracted teeth. Subsequently, half the sample was analysed using the rugosimeter before and after the application of ortophosphoric acid at 35% for 15 and the other half suing a Scansion Electronic microscope (SEM). The results obtained showed on the one hand that carbide cutters leave a smoother surfacer than diamond tipped cutters, and on the other that the smear layer is eliminated better by carbide cutters compared to diamond tipped cutters. Moreover, there are no major traumatic-type alterations at the level of the enamel affecting the microstructure after the use of carbide cutters.