Dual regulation of clock gene Per2 expression in discrete brain areas by the circadian pacemaker and methamphetamine‐induced oscillator in rats

Behavioral rhythms induced by methamphetamine (MAP) treatment in rats are independent of the circadian pacemaker in the suprachiasmatic nucleus (SCN). To know the site and mechanism of an underlying oscillation (MAP‐induced oscillator; MAO), extra‐SCN circadian rhythms in the discrete brain areas were examined in rats with and without the SCN. To fix the phase of MAO, MAP was supplied in drinking water at a restricted time of day for 14 days (R‐MAP) and subsequently given ad libitum (ad‐MAP). Plain water was given to the controls at the same restricted time (R‐Water). Clock gene Per2 expression was measured by a bioluminescence reporter in cultured brain tissues. In SCN‐intact rats, MAO was induced by R‐MAP and behavioral rhythms were phase‐delayed from the restricted time under ad‐MAP with relative coordination. Circadian Per2 rhythms in R‐MAP rats were not affected in the SCN but were slightly phase‐advanced in the olfactory bulb (OB), caudate–putamen (CPU) and substantia nigra (SN) as compared with R‐Water rats. Following SCN lesion, R‐MAP‐induced MAO phase‐shifted more slowly and did not show a sign of relative coordination. In these rats, circadian Per2 rhythms were significantly phase‐shifted in the OB and SN as compared with SCN‐intact rats. These findings indicate that MAO was induced by MAP given at a restricted time of day in association with phase‐shifts of the extra‐SCN circadian oscillators in the brain dopaminergic areas. The findings also suggest that these extra‐SCN oscillators are the components of MAO and receive dual regulation by MAO and the SCN circadian pacemaker.     

Low molecular weight pentastarch is more effective than crystalloid solution in goal-directed fluid management in patients undergoing major gastrointestinal surgery

Background

This prospective observational study compared the volume effect between hydroxyethyl starch (HES) and crystalloid solution and its context dependency in intraoperative goal-directed fluid management.

Methods

With institutional review board (IRB) approval, 35 patients undergoing major gastrointestinal surgery were enrolled. Fluid challenge consisting of 250 ml of either bicarbonate Ringer solution (BRS) or low molecular weight pentastarch (HES 70/0.5) was given to maintain stroke volume index >35 ml/m². The context of fluid challenge was classified as related to either epidural block (EB) or blood loss (BL) or as nonspecific. The primary end point was the interval between index fluid challenge and the next fluid challenge, and the secondary end point was the hemodynamic parameter at the end of fluid challenge. Differences in these parameters in each clinical context were compared between BRS and HES 70/0.5. A p value <0.05 was considered statistically significant.

Results

Eighty-eight, 77, and 127 fluid challenges were classified as related to EB and BL and as nonspecific, respectively. In the nonspecific condition, the median (range) interval after fluid challenge with HES 70/0.5 and BRS was 45 (11–162) min and 18 (8–44) min, respectively, and the difference was statistically significant. Also, mean arterial pressure and stroke volume index significantly increased, whereas stroke volume variation significantly decreased after fluid challenge with HES 70/0.5 compared with BRS. Such differences were not observed in the other situations.

Conclusions

HES 70/0.5 exerted larger volume effects than did crystalloid under nonspecific conditions. However, similar volume effects were observed during volume loss and extensive sympathetic blockade.     

Dexmedetomidine-induced atrioventricular block followed by cardiac arrest during atrial pacing: a case report and review of the literature

Sinus bradycardia is a well-known consequence of stimulation of presynaptic α₂ adrenergic receptors due the adminstration of dexmedetomidine. One of the most serious adverse effects of dexmedetomidine is cardiac arrest. Some cases demonstrating such an arrest due to the indiscriminate use of this drug were recently reported. We continuously administered dexmedetomidine to a 56-year-old male patient at a rate of 0.3 μg/kg/h (lower than the recommended dose) without initial dosing for sedation in an intensive care unit. The patient had undergone open cardiac surgery and atrial pacing was maintained at a fixed rate, 90/min. The PQ interval in electrocardiography gradually prolonged during the infusion; finally, complete atrioventricular block and subsequent cardiac arrest occurred. Immediate cardiopulmonary resuscitation was carried out, including re-intubation, and recovery of spontaneous circulation was attained 15 min after the event. The patient was discharged from hospital on the 25th postoperative day without any neurological complications.     

The safety and effectiveness profile of daily teriparatide in a prospective observational study in Japanese patients with osteoporosis at high risk for fracture: interim report

This postmarketing surveillance study assessed the safety and effectiveness of daily teriparatide treatment in patients with osteoporosis in a Japanese clinical setting. In this prospective, multicenter, observational study, patients with osteoporosis at high risk for fracture received subcutaneous injections of teriparatide (20 μg/day) for a maximum of 24 months. For this interim report, data from 1,671 patients were eligible for analysis at the cutoff date. The mean age was 75.3 years; 93 % of patients (1,552/1,671 patients) were women. There were 117 adverse drug reactions (ADRs) reported in 101 of 1,671 patients (6.04 %); the most common reported ADRs were nausea, dizziness, headache, and palpitations. No clinically significant safety issues were identified, although 5 serious ADRs were reported in 4/1,671 (0.24 %) patients. At 12 months, 71.9 % of patients remained on teriparatide treatment. From 1 month, there were rapid increases in the biomarkers of bone formation P1NP and, to a lesser extent, BAP. In contrast, increases in the biomarkers of bone resorption, serum NTX, urinary NTX, and TRACP5b, were smaller. After 12 months of treatment, there was an increase in bone mineral density at the lumbar spine, femoral neck, and total hip, and a decrease in the Visual Analog Scale score for back pain. The incidence of new vertebral and nonvertebral fractures was 1.21 % and 3.18 %, respectively. In conclusion, the favorable safety profile and effectiveness of teriparatide observed in this population of Japanese patients with osteoporosis were accompanied by relatively high persistence with treatment, which is a key factor in the success of osteoporosis treatment.     

Role of male pelvic floor muscles and anterior fibromuscular stroma in males on α1‐blocker treatment: A magnetic resonance imaging study

Dynamic motion of the pelvic floor muscles during voiding was analyzed using real‐time magnetic resonance imaging. To evaluate the contraction of the pelvic floor muscles, striated urethral sphincter distance, levator ani muscle thickness and anterior fibromuscular stroma distance were measured. The percent contraction of the striated urethral sphincter from before voiding to just before initiation of voiding was 14% in the normal group and 5% in the voiding dysfunction group. The percent contraction of the anterior fibromuscular stroma from before voiding to just before initiation of voiding was 11% in the normal group and 1% in the voiding dysfunction group; the percent contraction of the muscles was significantly greater in the normal group (P < 0.05). Striated urethral sphincter and anterior fibromuscular stroma contraction at initiation of voiding open the bladder neck and urethra. This plays an important role in the smooth initiation of voiding.     

Strength estimation of a moving 125Iodine source during implantation in brachytherapy: application to linked sources

This study sought to demonstrate the feasibility of estimating the source strength during implantation in brachytherapy. The requirement for measuring the strengths of the linked sources was investigated. The utilized sources were ¹²⁵I with air kerma strengths of 8.38–8.63 U (μGy m² h^–1). Measurements were performed with a plastic scintillator (80 mm × 50 mm × 20 mm in thickness). For a source-to-source distance of 10.5 mm and at source speeds of up to 200 mm s^–1, a counting time of 10 ms and a detector-to-needle distance of 5 mm were found to be the appropriate measurement conditions. The combined standard uncertainty (CSU) with the coverage factor of 1 (k = 1) was ∼15% when using a grid to decrease the interference by the neighboring sources. Without the grid, the CSU (k = 1) was ∼5%, and an 8% overestimation due to the neighboring sources was found to potentially cause additional uncertainty. In order to improve the accuracy in estimating source strength, it is recommended that the measurment conditions should be optimized by considering the tradeoff between the overestimation due to the neighboring sources and the intensity of the measured value, which influences the random error.     

Synchronization of masseter activity patterns between the right and left sides during chewing in healthy young males

Masseter activity patterns during chewing, which were quantitatively assessed using T₅₀ values, were compared between the right and left sides of healthy young males. Surface electromyograms were recorded from both masseters, and each participant was asked to chew four different agar samples at his own pace across two separate sessions. The four agar samples, each possessing differing textural properties, consisted of two normal and two distinctive agar varieties. The Pearson’s correlation coefficient was calculated for each pair of T₅₀ values to evaluate the degree of synchronization of activity patterns between both masseters. A three-way analysis of variance revealed significant main effects of the ‘participant’ and ‘experimental session’ factors, but not of the ‘test food’. The number of significant coefficients increased stepwise by increasing the number of chews per sequence. These results suggest the importance of the initial stages of chewing sequences in facilitating the synchronization of bilateral masseter activity patterns.