Brief neonatal handling alters sexually dimorphic behaviors in adult rats.

Several effects of neonatal handling on brain and behavior have been reported. We investigated the effects of neonatal handling on behaviors that have been shown to be sexually dimorphic in rats using an open-field test. "Gender differences" were observed in locomotor activity, exploratory behavior and grooming in the handled group. However, clear gender differences in these behaviors were not observed in the non-handled group. Our findings show that brief daily handling sessions (~ 1 min) in the first 2 weeks of postnatal life increased locomotor activity and exploratory behavior, and that these effects were more pronounced in females. Moreover, many rats in the non-handling group exhibited an increase in defecation relative to the handling group during the 10-min observation period. This suggests that the non-handling group experienced more stress in response to the novel open-field arena, and that this resulted in the absence of gender differences. Notably, this anxiety-related response was attenuated by neonatal handling. Our study underscores the impact of brief neonatal handling on sexually dimorphic behaviors, and indicates that caution should be exercised in controlling for the effects of handling between experimental groups, particularly in neurotoxicological studies that evaluate gender differences.

Effects of therapeutic ultrasound on range of motion and stretch pain.

[Purpose] This study aimed to clarify the effects of therapeutic ultrasound on range of motion and stretch pain and the relationships between the effects. [Subjects] The subjects were 15 healthy males. [Methods] Subjects performed all three interventions: (1) ultrasound (US group), (2) without powered ultrasound (placebo group), and (3) rest (control group). Ultrasound was applied at 3 MHz with an intensity of 1.0 W/cm(2) and a 100% duty cycle for 10 minutes. The evaluation indices were active and passive range of motion (ROM), stretch pain (visual analog scale; VAS), and skin surface temperature (SST). The experimental protocol lasted a total of 40 minutes; this was comprised of 10 minutes before the intervention, 10 minutes during the intervention (US, placebo, and control), and 20 minutes after the intervention. [Results] ROM and SST were significantly higher in the US group than in the placebo and control groups for the 20 minutes after ultrasound, though there was no change in stretch pain. [Conclusion] The effects of ultrasound on ROM and SST were maintained for 20 minutes after the intervention. The SST increased with ultrasound and decreased afterwards. Additionally, the SST tended to return to baseline levels within 20 minutes after ultrasound exposure. Therefore, these effects were caused by a combination of thermal and mechanical effects of the ultrasound.

Carvedilol improves uptake-1 in patients with systolic congestive heart failure.

BACKGROUND: The sympathetic nervous system (SNS) of the whole body, including cardiac sympathetic nerves, is activated in patients with severe congestive systolic heart failure (CHF). Carvedilol can improve clinical status in such patients. This study aimed to determine how carvedilol acts on the SNS to improve CHF. METHODS AND RESULTS: Ten subjects (New York Heart Association criteria III) were treated using carvedilol at 2.5 mg/d for 1 week. Before and after treatment, subjects walked on a treadmill for 6 minutes, and plasma concentrations of carvedilol, norepinephrine, and 3,4-dihydroxyphenyl glycol were measured. After treatment, norepinephrine was decreased at rest (3.2 ± 0.3 pmole/mL to 2.1 ± 0.4 pmole/mL, P < 0.05), while standing (5.4 ± 1.2 to 3.3 ± 0.7 pmole/mL, P < 0.01) and during exercise (6.5 ± 1.3 pmole/mL to 5.1 ± 1.1 pmole/mL, P < 0.05). Regression lines for percentage changes in norepinephrine and 3,4-dihydroxyphenyl glycol were compared before and after treatment, showing steeper slopes after treatment (P < 0.05). Plasma carvedilol concentrations (1.8 ± 0.3 ng/mL) did not reach ß-adrenoceptor-blocking levels of effect. CONCLUSIONS: Carvedilol is considered to improve function of uptake-1 for the whole-body SNS, including the cardiac SNS, and does not seem to block adrenoceptors at such low doses in CHF patients. However, both effects seem to work at high doses in clinical settings.

Prenatal exposure to bisphenol A impairs predator odor-induced fear behavior in young rat offspring.

OBJECTIVES: This study evaluated the changes in behaviors and the endocrine system in rat offspring at postnatal day 20 following prenatal exposure to bisphenol A (BPA), a major environmental endocrine disruptor. DESIGN: Using A predator odor (2,4,5-trimethylthiazoline [TMT]) as a stressor, I evaluate behavioral and endocrine responses to check whether the normal stress response is affected by BPA. MATERIALS AND METHODS: A low-dose group (BPA-L; 0.015 mg/kg/day) and a high-dose group (BPA-H; 1.5 mg/kg/day) were compared to assess dose dependency. The control group was not exposed to BPA. Spontaneous behaviors (rearing, ambulation, grooming, and freezing) were assessed in the presence or absence of TMT odor. RESULTS: In the control group, TMT odor increased freezing but not grooming behaviors. Conversely, in the BPA-H group, freezing was unchanged, but grooming behavior increased; however, increased freezing and grooming behaviors were observed following TMT odor exposure in the BPA-L group. In addition, blood corticosterone levels increased following TMT odor exposure in all three groups, but there was no difference between the BPA-exposure groups and the control group. Therefore, in the BPA-H group, despite the activation of the hypothalamus-pituitary-adrenal axis by TMT, freezing behavior did not increase, suggesting the absence of defensive behaviors. CONCLUSION: These findings suggest that prenatal exposure to high-dose BPA causes habituation to stress induced by the predator odor and alters the normal stress response in young rat offspring.

Analysis of the scapulohumeral rhythm and electromyography of the shoulder muscles during elevation and lowering: comparison of dominant and nondominant shoulders.

HYPOTHESIS: Assessment of whether elevation and lowering of the dominant and nondominant arms occur in a similar manner in healthy individuals is clinically important in terms of shoulder disorders. MATERIALS AND METHODS: We examined the scapulohumeral rhythm (SHR) and performed electromyography (EMG) for the middle deltoid, upper trapezius, lower trapezius, and lower part of the serratus anterior muscles of both shoulders in 18 healthy volunteers (14 men, 4 women) with a mean age of 24 years (range, 19-30 years). The participants randomly elevated and lowered either the right or left arm in the scapular plane, and the motion was measured using a 3-dimensional motion analyzer. RESULTS: The average angles of maximum arm elevation and scapular upward rotation were 130.3 degrees +/- 7.9 degrees and 32.2 degrees +/- 5.6 degrees, respectively, for dominant arms, and 130.8 degrees +/- 6.4 degrees and 31.8 degrees +/- 5.8 degrees, respectively, for nondominant arms. The SHR in each 10 degrees increment did not differ significantly between the dominant and nondominant arms in each participant during elevation (P = .337) and lowering (P = .1). A significant difference was found in the percentage integrated EMG (%IEMG) of the lower trapezius between the 2 shoulders (P < .049). DISCUSSION: If the kinematic difference is identified between both shoulders, we can predict the dysfunction or disorder in shoulder complex. Moreover, we should evaluate how shoulder muscles are used and whether the muscle becomes weak. CONCLUSIONS: Healthy individuals elevate and lower the dominant and nondominant shoulders in a similar kinematical pattern despite 3 of 4 muscles indicating different EMG activities between both shoulders.

Morphological evaluation of the human pyramidal tract: tapering of axons.

It is generally accepted that nerve fiber conduction velocity is directly proportional to the fiber diameter under the condition, based on a supposition, that the transverse area of axons is normally maintained constant. Using an ideal preparation method for the purpose of axonal discrimination, we examined 43 human spinal cords after making transverse sections at the cervical, thoracic, lumbar and sacral levels and found a tapering of the axons in the lateral pyramidal tract, as the cross-sectional area of the pyramidal axons showed a definite decrease from the cervical to the sacral levels. Our results contradict the supposition that the transverse area of axons is normally maintained constant, which has for a long time been believed to be true without any evidence for it.

Excretions of urinary albumin and various proteins increase in hypertension.

AIMS: Hypertension causes proteinuria and is an important factor in the progress of renal dysfunction. Increases in various proteins in urine are caused by malfunction of the glomerulus and the renal tubules. In the present study, the effects of hypertension on urinary excretion levels of various proteins were investigated to show the tubular cell malfunction in hypertensive patients. METHODS AND SUBJECTS: The subjects included 55 non-diabetic hypertensive patients without previous treatment and 42 normotensive individuals without microalbuminuria. Total urinary protein/creatinine ratio was measured, and urinary proteins were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). FINDINGS: Total urinary protein/creatinine ratio was higher in hypertensive patients than in normotensive individuals (122.0+/-11.0 vs. 60.6+/-3.1 mg/gCr; p<0.001). SDS-PAGE resolved 15 protein fractions from the urine of both groups. Thirteen fractions were more intensely stained in samples from the hypertensive than from the normotensive. Two fractions did not differ between the groups. Hypertension increased the urinary excretion of various proteins including proteins of less than 40 kDa, called tubular proteins, in addition to albumin. CONCLUSIONS: Hypertension differently influenced the excretion of each urinary protein fraction. Tubular malfunction should be considered in hypertensive patients in addition to glomerular malfunction.

Prenatal bisphenol A exposure is associated with medial amygdala neuron hyperresponsiveness to predator odor in rats.

Perinatal exposure to bisphenol A (BPA) causes several alterations in brain function and behavior. In previous studies, we showed that prenatal treatment with low-level BPA impaired gender-specific behavior, enhanced depression-like behavior, and augmented behavioral responses to predator odor in rats. On this premise, we hypothesized that BPA-treated rats were more susceptible to predator odor stress. To test the potential neural mechanism underlying this effect, we conducted an electrophysiological study of neurons in the medial amygdala-a regional component of the olfactory pathway with high estrogen and androgen receptor expression, and thus a potential target of BPA-in rats exposed to BPA. Extracellular recordings were obtained during the presentation of 3 plant odors and 3 predator odorants. Odor-responsive neurons in BPA-exposed rats showed greater activity in response to fox odor than did those in control rats. This finding complements the results of our previous behavioral study in which BPA-exposed rats exhibited enhanced avoidance behavior in response to fox odor. Given the close relationship between olfactory signaling and the stress response system, we suspect that BPA modifies the olfactory pathway at the level of the medial amygdala and thus modulates the corresponding stress response.

Fluorescence and chemiluminescence behavior of distyrylbenzene bearing two arms of dipicolylaminomethyl groups: Interactions with zinc ion and ATP.

The absorption and fluorescence spectral study of the distyrylbenzene bearing two arms of the dipicolylaminomethyl groups, the effective ligands for Zn2+, was studied in the presence of Zn2+ and ATP. Upon complexation of the distyrylbenzene with zinc ions in acetonitrile, enhancement of the fluorescence intensity was observed due to inhibition of intramolecular PET (photo-induced electron transfer) quenching, but no effect was found in aqueous media because the equilibrium laid to the free form of the ligands. In contrast, the addition of ATP disodium salt was effective to enhance the fluorescence intensity of the combination of the distyrylbenzne and Zn2+ in aqueous media. This assembly was applied to the peroxyoxalate chemiluminescence system and a significant increase in the intensity was observed, which provides a potential detection for ATP by chemiluminescence.

Prenatal exposure to bisphenol A impairs sexual differentiation of exploratory behavior and increases depression-like behavior in rats.

Perinatal exposure to bisphenol A (BPA, 0.1 and 1 ppm in drinking water applied to mother rats for 6 weeks) has been shown to impair the sexual differentiation in exploratory behavior, but the exact critical period of this disrupting effect is still unknown. In this study, we examined the effects of prenatal exposure to BPA (0.1 ppm in drinking water applied to dams during the final week of pregnant) on emotional and learning behaviors in addition to exploratory behavior. Estimated daily intake was 15 microg/kg/day, below the reference dose (RfD) in the United States and the daily tolerable intake (TDI) in Japan (50 microg/kg/day). The rats were successively tested in open-field test, elevated plus maze test, passive avoidance test and forced swimming test during development from 6 to 9 weeks of juvenile period. Prenatal exposure to BPA mainly affected male rats and abolished sex differences in rearing behavior in the open-field test and struggling behavior in the forced swimming test. BPA increased the immobility of male rats in the forced swimming test. The avoidance learning and behaviors in the elevated plus maze were not affected. The present study demonstrates that male rats at the final week of prenatal period are sensitive to BPA, which impairs sexual differentiation in rearing and struggling behavior and facilitate depression-like behavior.

Simultaneous analysis of human plasma catecholamines by high-performance liquid chromatography with a reversed-phase triacontylsilyl silica column.

The clinical importance of simultaneous analysis of 3,4-dihydroxyphenylglycol with other human plasma catecholamines has been investigated to better understand the sympathetic nervous system. However, previous reports have had analytical difficulties with both resolution and extraction. The current study uses a reversed-phase triacontylsilyl silica (C30) column under the mobile phase condition without ion-pair reagents to separate catecholamines and their metabolites, with above 91% recoveries for intra-assay, above 85% for inter-assay, and less than 10% (n=5) coefficient of variation. Lower detection limits (S/N=4) and quantification limits (S/N=6) were 40 and 100 pg/mL for norepinephrine, 3,4-dihydroxyphenylglycol, and 3,4-dihydroxyphenylalanine, 10 and 20 pg/mL for epinephrine, 10 and 40 pg/mL for dopamine. Linear ranges were from 40 to 5000 pg/mL for norepinephrine and 3,4-dihydroxyphenylalanine, from 100 to 5000 pg/mL for 3,4-dihydroxyphenylglycol, and from 10 to 2000 pg/mL for epinephrine and dopamine. The C30 column may prove clinically useful, as it provides a convenient and simultaneous method of evaluation of human plasma catecholamines.

Catalytic asymmetric desymmetrization of cyclic meso-1,3- and 1,4-diols by a phosphinite derivative of quinidine.

Asymmetric monobenzoylation reactions of cyclic meso-1,3- and 1,4-diols were catalyzed by a phosphinite derivative of quinidine to afford the corresponding monobenzoylated diol with good yield and enantioselectivity. [reaction: see text]

Prenatal low-dose bisphenol A enhances behavioral responses induced by a predator odor.

Bisphenol A (BPA) is an environmental endocrine disrupter (EED). Previous studies by our group showed that pre- and postnatal administration of low-level BPA induced depression-like behavior in rats. In this study, we evaluated the effects of prenatal BPA on behavioral responses to a predator odor by using a novel cross-form apparatus consisting of 4 plastic chambers. On the first day, nothing was placed into the chambers (Session 1). On the second day, a predator odor (fox odor) was located in separate chambers at 2 opposite corners of the apparatus (Session 2). Pregnant Wistar rats were exposed to low-dose BPA (less than the reference dose) during the 7 days just before birth, and the offspring of the treated rats were evaluated as adults. The locomotor activity and avoidance response of each rat on both test days were compared. The control and BPA groups showed reduced locomotor activity in the presence of the predator odor, but the odor-avoidance response was significant only in the BPA rats. The BPA-exposed rats were obviously sensitive to the predator odor. These results suggest that prenatal BPA exposure has an amplifying effect on avoidance responses to predator odor stress.

Different coronary blood flow increase in left ventricular hypertrophy due to hypertension compared to hypertrophic cardiomyopathy at elevated heart rate.

Coronary vasodilator reserve (CVR) is reduced in patients with left ventricular hypertrophy (LVH). However, it is not clear whether there is any difference between the coronary blood flow increase in LVH caused by hypertension (HTH) and that caused by hypertrophic cardiomyopathy (HCM) when the heart rate increases. In this study, 16 subjects with HTH, 10 subjects with HCM, and 10 subjects with normotension (NT) were investigated. Average peak velocities at rest, at pacing, and at dilatation were measured using a Doppler catheter placed at the left descending coronary artery to calculate coronary blood flow (CBF) and CVR. CVR at rest was identical in the HTH and HCM groups, and in both cases was lower than the resting CVR in NT subjects. There were significant differences in the CVR values at a pacing rate of 120 beats/min among the groups. These values were lowest in HCM, highest in NT, and intermediary in HTH subjects. And the percent increase in CBF in HCM at that pacing rate was higher than that in HTH (p < 0.05) or NT (p < 0.05). There was no difference in the percent increase in CBF at this pacing rate between the HTH and NT groups. The effects of elevated heart rate on the percent increase in CBF were different between the HTH and HCM groups. We conclude that cardiac hypertrophy has qualitatively different effects on coronary circulation depending on whether patients have HTH or HCM.

Halogenovinyl Sulfones. 6.(1) Synthesis of Condensed Heterocycles by Diastereoselective Intramolecular Diels-Alder Reactions of Sulfonyl-Substituted Trienes.

Sulfonyl trienes having a chiral center on the allyl carbon of the diene moiety were prepared from L-amino acid as chiral building blocks. Intramolecular Diels-Alder reaction of the sulfonyl trienes having E-geometry on the diene moiety proceeded on the si-face and exo-selectively to give cis-isoindoles as a sole product in good yields. But using the sulfonyl trienes having Z-geometry on the diene part, the ratio of the diastereomers of the products decreased to about 80:20. The observed stereoselectivity can be explained by calculations with semiempirical and ab initio methods.

[Introduction of team-based learning to the pharmacy experiential practice course for first-year pharmacy students].

In recent years, the number of high school graduates has decreased, whereas the number of new pharmacy schools has increased substantially. Therefore, pharmacy schools these days accommodate students from diverse backgrounds in terms of basic knowledge, study skills, and/or their motivation to be pharmacists. To address this issue, we developed a mandatory 10-day course named "Pharmacy experiential practice" for the first-year students. The program trains students in basic pharmacy calculation skills and communication skills, and provides an insight into how these skills can be applied in actual pharmacy practice. The program includes 5 themes, namely, "Compounds", "Solutions", "Infusions", "Nutrition" and "Communication". Each theme, except "Communication", was conducted for 2 days 3 hour calculation practice in class and 3 hour pharmacy experiential practice each day. In the calculation class, we introduced team-based learning, which enhanced the students for interactive learning in the classes. In the pharmacy experiential practices, the students were trained not only to apply their calculation skills to pharmacy practice in each theme, but also to understand the importance of basic science knowledge in strengthening the foundations for their calculation skills. Course evaluation showed that students experienced the effectiveness of interactive study and that they realized the importance of pharmacy practice and the basic sciences that they had learnt. Some students commented that their motivation to become pharmacists increased after this course.

Effects of therapeutic ultrasound on intramuscular blood circulation and oxygen dynamics.

PURPOSE: This study aimed to clarify the effects of therapeutic ultrasound on intramuscular local blood circulation (and oxygen dynamics) using near-infrared spectroscopy (NIRS). PARTICIPANTS: The participants were 11 healthy males. METHODS: All participants performed all three trials; (1) the ultrasound (US group), (2) without powered ultrasound (placebo group), and (3) rest (control group). Ultrasound was applied at 3 MHz, 1.0 W/cm(2), and 100% duty cycle for 10 minutes. Evaluation index were oxygenated, deoxygenated, and total hemoglobin (Hb) concentrations in the intramuscular and skin surface temperature (SST). The experimental protocol was a total of 40 minutes, that is, 10 minutes before trial (rest), 10 minutes during the trial (ultrasound, placebo, and control), and 20 minutes after trial (rest). The NIRS and SST data collected before and after the trial were divided into 5 minutes intervals for further analysis. RESULTS: Oxygenated and total hemoglobin levels were significantly higher in the US group than in the placebo and control groups for the 20 minutes after ultrasound (p < 0.01). The SST was significantly higher in the US group than in the control for 15 minutes after ultrasound (p < 0.05), while it was significantly lower in the placebo group than in the US and control groups for 20 minutes after the trials (p < 0.01). CONCLUSION: The effects of ultrasound were maintained for 20 minutes after the trial on intramuscular blood circulation and oxygen dynamics. These effects were caused by a combination of thermal and mechanical effects of the ultrasound.

Postnatal exposure to low-dose bisphenol A influences various emotional conditions.

Bisphenol A (BPA) is one of the 'environmental endocrine disrupters' (EEDs) released by plastics and resin known to interfere with hormonal responses. In this study, female Wistar rats were exposed to low-dose BPA (24 µg/kg/day) during 7 days after giving birth. The male and female offspring, exposed to the BPA through lactation, were evaluated using an open field test (OFT) at the age of six weeks, an elevated plus maze test (EPM) at seven weeks, and a forced swimming test (FST) at nine weeks. The OFT indicated that females were more active than males, and that BPA selectively increased rearing duration in males, thereby eliminating the gender effect. The results of EPM showed that BPA did not enhance the anxiety-like action; rather, it was associated with an anxiolytic-like action in females. In the FST, not only there was an increase in the immobility time, but also there was reduction of latency observed in BPA rats. It indicated that the depression-like responses were clearly enhanced by the postnatal exposure. Altogether, these data suggest that low-dose BPA ingested by neonates through breastfeeding may cause persistent aberrant behaviors that are relevant to emotions.

Enantioselective acylation of 1,2- and 1,3-diols catalyzed by aminophosphinite derivatives of (1S,2R)-1-amino-2-indanol.

A phosphinite derivative that can be easily prepared in two steps from commercially available aminoindanol was found to be an effective catalyst for enantioselective acylation of diols. For the asymmetric desymmetrization of meso-1,2-diols, the corresponding monoester was obtained in up to 95% ee from the reaction in the presence of 5 mol % catalyst.

Effects of C-reactive protein on CC chemokine receptor 2-mediated chemotaxis of monocytes.

Periodontal infections can increase patients' serum C-reactive protein (CRP) level, which is a predictive marker of future cardiovascular events. Serum CRP may be a key mediator associating periodontitis with cardiovascular disease. It is not yet clarified whether the chemotactic activity of monocytes changes with increased serum CRP. This study investigated the influence of CRP on monocyte chemotaxis and the effects of CRP on CC chemokine receptor 2 (CCR2) expression by monocytes in vitro. Monocyte cell line THP-1 was cultured with human recombinant CRP of different final concentrations, which were 2, 4, 6, 8, and 10 mg/L, respectively. After 24 h incubation, Transwell chambers were applied to analyze the chemotactic activity of pretreated monocytes. Flow cytometry analysis and real-time reverse transcription-polymerase chain reaction (RT-PCR) were applied to detect the CCR2 protein and gene expression levels. In Transwell chambers, more cells were attracted in CRP-pretreated groups than that of blank control with no CRP (p<0.05). The chemotaxis activity was stronger in higher CRP concentration groups than lower ones (p<0.05). The CCR2 protein and mRNA expression was increased in a CRP concentration-dependent manner (p<0.05). CRP stimulation may induce CCR2 overexpression on monocytes and then promote the chemotaxis ability of monocytes. This result suggests that increased serum CRP concentration of periodontitis patients may be associated with high risk of cardiovascular disease.