Differential Effects of the Lateral Hypothalamus Lesion as an Origin of Orexin and Blockade of Orexin-1 Receptor in the Orbitoftontal Cortex and Anterior Cingulate Cortex on Their Neuronal Activity

Several studies revealed that orexins may take part in the regulation of the different forms of affective and cognitive processes during wakefulness. The orbitofrontal cortex (OFC) and anterior cingulate cortex (ACC) as an important part of the prefrontal cortex (PFC) have a crucial role in cognitive processes such as reward and decision-making and has a high density of orexin receptor type 1 (OX1Rs). In the present study, to find out the role of OX1Rs in the OFC neurons firing rate, the OX1Rs were inhibited in this area after a10-min baseline recording. In the second part, the lateral hypothalamus (LH) as the main source of orexinergic neurons was inhibited and its effect on the firing rate and activity pattern of the ACC or OFC neurons were detected by using single-unit recording technique in the rats. Results showed that blockade of OX1Rs in the OFC could excite 8 and inhibit 1 neuron out of 11. Besides, the blockade of OX1Rs in the ACC could excite 6 and inhibit 3 neurons out of 10. Also, LH inactivation excited 5 out of 12 neurons and inhibited 6 neurons in the ACC. It excited 8 and inhibited 6 neurons out of 14 in the OFC. These data suggested that blockade of the OX1Rs excited 72% of the neurons, but LH inactivation had an exciting effect on just 50% of neurons in two main subregions of PFC. It seems that the PFC neurons receive the orexinergic inputs from the LH and indirectly from other sources.

Homeostatic regulation of NREM sleep, but not REM sleep, in Australian magpies

Study Objectives We explore NREM and REM sleep homeostasis in Australian magpies (Cracticus tibicen tyrannica). We predicted that magpies would recover lost sleep by spending more time in NREM and REM sleep, and by engaging in more intense NREM sleep as indicated by increased slow-wave activity (SWA). Methods Continuous 72-h recordings of EEG, EMG and tri-axial accelerometry, along with EEG spectral analyses, were performed on wild-caught Australian magpies housed in indoor aviaries. Australian magpies were subjected to two protocols of night-time sleep deprivation: full 12-h night (n = 8) and first 6-h half of the night (n = 5), which were preceded by a 36-h baseline recording and followed by a 24-h recovery period. Results Australian magpies recovered lost NREM sleep by sleeping more, with increased NREM sleep consolidation, and increased SWA during recovery sleep. Following 12-h of night-time sleep loss, magpies also showed reduced SWA the following night after napping more during the recovery day. Surprisingly, the magpies did not recover any lost REM sleep. Conclusions Only NREM sleep is homeostatically regulated in Australian magpies with the level of SWA reflecting prior sleep/wake history. The significance of emerging patterns on the apparent absence of REM sleep homeostasis, now observed in multiple species, remains unclear.

Occipitoatlantal decompression and noninvasive vagus nerve stimulation slow conduction velocity through the atrioventricular node in healthy participants

Context Management of atrial fibrillation includes either rhythm control that aims at establishing a sinus rhythm or rate control that aims at lowering the ventricular rate, usually with atrioventricular nodal blocking agents. Another potential strategy for ventricular rate control is to induce a negative dromotropic effect by augmenting cardiac vagal activity, which might be possible through noninvasive and nonpharmacologic techniques. Thus, the hypothesis of this study was that occipitoatlantal decompression (OA-D) and transcutaneous auricular vagus nerve stimulation (taVNS) not only increase cardiac parasympathetic tone as assessed by heart rate variability (HRV), but also slow atrioventricular conduction, assessed by the PQ-interval of the electrocardiogram (EKG) in generally healthy study participants without atrial fibrillation. Objectives To test whether OA-D and/or transcutaneous taVNS, which have been demonstrated to increase cardiac parasympathetic nervous system activity, would also elicit a negative dromotropic effect and prolong atrioventricular conduction. Methods EKGs were recorded in 28 healthy volunteers on three consecutive days during a 30 min baseline recording, a 15 min intervention, and a 30 min recovery period. Participants were randomly assigned to one of three experimental groups that differed in the 15 min intervention. The first group received OA-D for 5 min, followed by 10 min of rest. The second group received 15 min of taVNS. The intervention in the third group that served as a time control group (CTR) consisted of 15 min of rest. The RR- and PQ-intervals were extracted from the EKGs and then used to assess HRV and AV-conduction, respectively. Results The OA-D group had nine participants (32.1%), the taVNS group had 10 participants (35.7%), and the CTR group had nine participants (32.1%). The root mean square of successive differences between normal heartbeats (RMSSD), an HRV measure of cardiac parasympathetic modulation, tended to be higher during the recovery period than during the baseline recording in the OA-D group (mean ± standard error of the mean [SEM], 54.6 ± 15.5 vs. 49.8 ± 15.8 ms; p<0.10) and increased significantly in the taVNS group (mean ± SEM, 28.8 ± 5.7 vs. 24.7 ± 4.8 ms; p<0.05), but not in the control group (mean ± SEM, 31.4 ± 4.2 vs. 28.5 ± 3.8 ms; p=0.31). This increase in RMSSD was accompanied by a lengthening of the PQ-interval in the OA-D (mean ± SEM, 170.5 ± 9.6 vs. 166.8 ± 9.7 ms; p<0.05) and taVNS (mean ± SEM, 166.6 ± 6.0 vs. 162.1 ± 5.6 ms; p<0.05) groups, but not in the control group (mean ± SEM, 164.3 ± 9.2 vs. 163.1 ± 9.1 ms; p=0.31). The PQ-intervals during the baseline recordings did not differ on the three study days in any of the three groups, suggesting that the negative dromotropic effect of OA-D and taVNS did not last into the following day. Conclusions The lengthening of the PQ-interval in the OA-D and taVNS groups was accompanied by an increase in RMSSD. This implies that the negative dromotropic effects of OA-D and taVNS are mediated through an increase in cardiac parasympathetic tone. Whether these findings suggest their utility in controlling ventricular rates during persistent atrial fibrillation remains to be determined.

RADIOGRAPHIC EVALUATION OF TELESCOPIC PIER ABUTMENTS IN MANDIBULAR DISTAL EXTENSION CASES

Purpose: The aim of this clinical study is to compare the effect of both definitive partial dentures and telescopic partial dentures on bone height changes around the terminal abutments in mandibular distal extension cases with pier abutment. Materials and Methods: Fourteen mandibular Kennedys Class I classification with pier abutment patients were divided into two equal groups. First group (I) received definitive metal-frame removable partial dentures (RPD), while the second group (II) received telescopic RPD. The supporting bone height around the terminal abutments was radiographically evaluated. Next to baseline recording following denture insertion, bone height measurements were obtained at regular recall follow-up appointments of 6, 12, 18 and 24 months. Radiographic evaluation was carried outusing the Digora system and customized acrylic template constructed for each patient individually. The linear measurement system supplied by the Digora machine software was utilized for recording bone height changes mesial and distal to the main terminal abutments. Results: Comparison was performed between definitive and telescopic groups utilizing independent t-test and resulted in differencesof no significant for all follow-up recalls (P value > 0.05). Conclusion:Definitive RPD and telescopic RPD appeared to besuccessful both clinically and biologically. However, Telescopic RPD proved to be superior to the definitive one regarding bone height measurements.

Enduring effects of perinatal nicotine exposure on murine sleep in adulthood

The long-term consequences of early life nicotine exposure are poorly defined. Approximately 8–10% of women report smoking during pregnancy, and this may promote aberrant development in the offspring. To this end, we investigated potential enduring effects of perinatal nicotine exposure on murine sleep and affective behaviors in adulthood (~13–15 wk of age) in C57Bl6j mice. Mothers received a water bottle containing 200 µg/ml nicotine bitartrate dihydrate in 2% wt/vol saccharin or pH-matched 2% saccharin with 0.2% (vol/vol) tartaric acid throughout pregnancy and before weaning. Upon reaching adulthood, offspring were tested in the open field and elevated plus maze, as well as the forced swim and sucrose anhedonia tests. Nicotine-exposed male (but not female) mice had reduced mobility in the open field, but no differences were observed in anxiety-like or depressive-like responses. Upon observing this male-specific phenotype, we further assessed sleep-wake states via wireless EEG/EMG telemetry. Following baseline recording, we assessed whether mice exposed to nicotine altered their homeostatic response to 5 h of total sleep deprivation and whether nicotine influenced responses to a powerful somnogen [i.e., lipopolysaccharides (LPS)]. Males exposed to perinatal nicotine decreased the percent time spent awake and increased time in non-rapid eye movement (NREM) sleep, without changes to REM sleep. Nicotine-exposed males also displayed exaggerated responses (increased time asleep and NREM spectral power) to sleep deprivation. Nicotine-exposed animals additionally had blunted EEG slow-wave responses to LPS administration. Together, our data suggest that perinatal nicotine exposure has long-lasting effects on normal sleep and homeostatic sleep processes into adulthood.

The Effect of Electroacupuncture with Different Frequencies on Muscle Oxygenation in Humans

The aim of the present study was to investigate the effect of electroacupuncture (EA) with different frequencies on muscle oxygenation in humans. The subjects were 8 healthy male volunteers. Muscle oxygenation was measured using near-infrared spectroscopy (NIRS). Blood pressure (BP) and heart rate (HR) were monitored simultaneously. After baseline recording, EA was given for 15 min and recovery was measured for 20 minutes. The procedure of EA at 1 Hz, at 20 Hz, and at control followed in the same subjects. Tissue oxygenation index (TOI) decreased during EA at 20 Hz (P<0.05) and increased during the recovery period. Normalized tissue hemoglobin index (nTHI) also decreased during EA at 20 Hz and increased during the recovery period (P<0.05), whereas TOI and nTHI in the EA at 1 Hz did not change significantly throughout the experiment. The peak TOI and nTHI values at 20 Hz during the recovery period were higher than the values at 1 Hz and in the control (P<0.05). BP and HR remained constant. These data suggest that the supply of oxygen to muscle decreased during EA at 20 Hz and increased after EA at 20 Hz, without any changes in HR and BP.

Changes in Esophageal and Lower Esophageal Sphincter Motility with Healthy Aging

Background & Aims: Swallowing difficulties become increasingly prevalent in older age. Differences exist in lower esophageal sphincter (LES) function between older and younger patients with dysphagia, but the contribution of aging per se to these is unclear.Methods: Esophageal motor function was measured using high resolution manometry in older (aged 81±1.7 yrs) and younger (23±1.7 yrs) asymptomatic healthy adults. After baseline recording, motility was assessed by swallowing boluses of liquid (right lateral and upright postures) and solids. Basal LES pressure, integrated relaxation pressure, distal esophageal peristaltic amplitude and velocity were measured. Data are presented as mean ą SEM.Results: Despite a trend for lower basal LES pressure (15.7±2.9 mmHg vs. 21.0±0.2mmHg; P=0.08),completeness of LES relaxation was reduced in older subjects (liquid RL: P=0.003; UR: P=0.007; solid: P=0.03), with higher integrated relaxation pressure when upright (liquid: 6.9±1.1 vs. 3.1±0.4 mmHg; P=0.01; solids: 8.1±1.1 vs. 3.6±0.3 mmHg; P=0.001) and a longer time to recovery after liquid boluses (right lateral: P=0.01; upright: P=0.04). In young, but not older adults, esophageal peristaltic velocity was increased when upright (3.6±0.2 cm/sec; P=0.04) and reduced with solids (3.0±0.1 cm/sec; P=0.03). Distal contraction amplitude was higher with solids in the young (51.8±7.9 mmHg) but not older (41.4±6.2 mmHg; P=0.03) individuals. In elderly subjects, the distal contractile integral was higher with liquid swallows in the upright posture (P=0.006).Conclusion: There are subtle changes in LES function even in asymptomatic older individuals. These agerelated changes may contribute to the development of dysphagia.

Distension of the esophagogastric junction augments triggering of transient lower esophageal sphincter relaxation

Patients with gastroesophageal reflux disease show an increase in esophagogastric junction (EGJ) distensibility and in frequency of transient lower esophageal sphincter relaxations (TLESR) induced by gastric distension. The objective was to study the effect of localized EGJ distension on triggering of TLESR in healthy volunteers. An esophageal manometric catheter incorporating an 8-cm internal balloon adjacent to a sleeve sensor was developed to enable continuous recording of EGJ pressure during distension of the EGJ. Inflation of the balloon doubled the cross-section of the trans-sphincteric portion of the catheter from 5 mm OD (round) to 5 × 11 mm (oval). Ten healthy subjects were included. After catheter placement and a 30-min adaptation period, the EGJ was randomly distended or not, followed by a 45-min baseline recording. Subjects consumed a refluxogenic meal, and recordings were made for 3 h postprandially. A repeat study was performed on another day with EGJ distension status reversed. Additionally, in one subject MRI was performed to establish the exact position of the balloon in the inflated state. The number of TLESR increased during periods of EGJ distension with the effect being greater after a meal [baseline: 2.0(0.0–4.0) vs. 4.0(1.0–11.0), P=0.04; postprandial: 15.5(10.0–33.0) vs. 22.0(17.0–58.0), P=0.007 for undistended and distended, respectively]. EGJ distension augments meal-induced triggering of TLESR in healthy volunteers. Our data suggest the existence of a population of vagal afferents located at sites in/around the EGJ that may influence triggering of TLESR.

Cerebral oximetry and stump pressure as indicators for shunting during carotid endarterectomy: comparative evaluation

The purpose of this work is to investigate the correlation between regional oxygen saturation (rSO2) changes and stump pressure (SP) during cross-clamping of the internal carotid artery in carotid endarterectomy (CEA) and verify the perspectives of rSO2 to become a criterion for shunting. Sixty consecutive CEAs under general anesthesia were studied prospectively. Selective shunting was based on SP ≤40 mmHg exclusively. Regression analysis with high order terms and receiver operating characteristic analysis were performed to investigate the association between ΔrSO2(%) and SP and to determine an optimal ΔrSO2(%) threshold for shunt insertion. A quadratic association between ΔrSO2(%) and SP was documented regarding the baseline to one and five minutes after cross-clamping intervals. A cut-off of 21 and 10.1% reduction from the baseline recording was identified as optimal for the distinction between patients needed or not a shunt regarding the first and fifth minute after cross-clamping, respectively. In conclusion, cerebral oximety reflects sufficiently cerebral oxygenation during CEA compared with SP, providing a useful mean for cerebral monitoring.

Expression of the long form of the prolactin receptor in magnocellular oxytocin neurons is associated with specific prolactin regulation of oxytocin neurons

Magnocellular neurons of the supraoptic (SON) and paraventricular nuclei (PVN) show considerable plasticity during pregnancy and lactation. Prolactin receptors (PRL-R) have been identified in both these nuclei. The aim of this study was to investigate the cell type(s) expressing mRNA for the long form of prolactin receptor (PRL-RL) and to determine whether patterns of expression change during pregnancy and lactation. In addition, we examined effects of prolactin on excitability of oxytocin and vasopressin neurons. Sections from brains of nonpregnant, pregnant, and lactating rats were hybridized with an 35S-labeled probe to label PRL-RL mRNA together with digoxigenin-labeled probes to detect either oxytocin or vasopressin mRNA. In the SON, PRL-RL mRNA was predominantly colocalized with oxytocin mRNA, with over 80% of oxytocin neurons positive for PRL-RL mRNA. Very few (<10%) vasopressin neurons expressed PRL-RL mRNA. In the PVN, PRL-RL mRNA was also predominantly found in oxytocin neurons, and the proportion of PRL-RL-positive oxytocin neurons increased significantly during pregnancy and lactation. As in the SON, relatively few vasopressin cells contained PRL-RL mRNA. For in vivo electrophysiology, nonpregnant rats were anesthetized, and then extracellular single neuron activity was recorded in identified oxytocin and vasopressin neurons. After a period of baseline recording, the effect of prolactin (1 μg icv) on firing rate was examined. Prolactin treatment of nonpregnant rats induced a significant decrease in firing rates of oxytocin neurons. There was no effect of prolactin on the activity of vasopressin neurons. Together, these data provide strong evidence that prolactin directly and specifically regulates activity of oxytocin neurons.