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Biomedical subjects

R Kawahara

Publications and source records attributed to R Kawahara.

At least 19 recordsLinked to original sources

Hippocampal synapsin I, growth-associated protein-43, and microtubule-associated protein-2 immunoreactivity in learned helplessness rats and antidepressant-treated rats.

Learned helplessness rats are thought to be an animal model of depression. To study the role of synapse plasticity in depression, we examined the effects of learned helplessness and antidepressant treatments on synapsin I (a marker of presynaptic terminals), growth-associated protein-43 (GAP-43; a marker of growth cones), and microtubule-associated protein-2 (MAP-2; a marker of dendrites) in the hippocampus by immunolabeling. (1) Learned helplessness rats showed significant increases in the expression of synapsin I two days after the attainment of learned helplessness, and significant decreases in the protein expression eight days after the achievement of learned helplessness. Subchronic treatment of naïve rats with imipramine or fluvoxamine significantly decreased the expression of synapsin I. (2) Learned helplessness increased the expression of GAP-43 two days and eight days after learned helplessness training. Subchronic treatment of naïve rats with fluvoxamine but not imipramine showed a tendency to decrease the expression of synapsin I. (3) Learned helplessness rats showed increased expression of MAP-2 eight days after the attainment of learned helplessness. Naïve rats subchronically treated with imipramine showed a tendency toward increased expression of MAP-2, but those treated with fluvoxamine did not. These results indicate that the neuroplasticity-related proteins synapsin I, GAP-43, and MAP-2 may play a role in the pathophysiology of depression and the mechanisms of antidepressants.

Analysis of Variance↗

Serine racemase binds to PICK1: potential relevance to schizophrenia.

Accumulating evidence from both genetic and clinico-pharmacological studies suggests that D-serine, an endogenous coagonist to the NMDA subtype glutamate receptor, may be implicated in schizophrenia (SZ). Although an association of genes for D-serine degradation, such as D-amino acid oxidase and G72, has been reported, a role for D-serine in SZ has been unclear. In this study, we identify and characterize protein interacting with C-kinase (PICK1) as a protein interactor of the D-serine synthesizing enzyme, serine racemase (SR). The binding of endogenous PICK1 and SR requires the PDZ domain of PICK1. The gene coding for PICK1 is located at chromosome 22q13, a region frequently linked to SZ. In a case-control association study using well-characterized Japanese subjects, we observe an association of the PICK1 gene with SZ, which is more prominent in disorganized SZ. Our findings implicating PICK1 as a susceptibility gene for SZ are consistent with a role for D-serine in the disease.

Adult↗

Pregnenolone and dehydroepiandrosterone administration in neonatal rats alters the immunoreactivity of hippocampal synapsin I, neuropeptide Y and glial fibrillary acidic protein at post-puberty.

It is well documented that neurosteroids administered during the neonatal period influence the development of several brain systems. In our previous study, pregnenolone administered to rats during the neonatal period altered adenosinergic and dopaminergic functions in the striatum and cerebral cortex. The present study examined the effects of the treatment with pregnenolone and dehydroepiandrosterone (DHEA) from the postnatal day (P) 3-P7 on synapsin I (a marker for presynaptic terminals) and glial fibrillary acidic protein (GFAP: a marker for astroglia) levels in the hippocampus of Sprague-Dawley rats at 3 and 7 weeks of age. In addition, neuropeptide Y and dynorphin A immunoreactivity was measured. The administration of pregnenolone and DHEA to neonatal rats significantly altered the expression of synapsin I in the dentate gyrus and CA3 region at post-puberty but not at pre-puberty. A significantly greater expression of GFAP-immunoreactive astrocytes or processes was demonstrated in the pregnenolone- and DHEA-treated groups at both pre-puberty and post-puberty. A significant increase in the number and size of GFAP-immunoreactive astrocytes and in the extension of arborization was seen in the overall hippocampus. The number of neuropeptide Y-positive cells in the hilus region was also significantly increased in the neurosteroid-treated group at post-puberty. No differences were detected in dynorphin A immunoreactivity among the experimental groups. These results of this study suggest that pregnenolone and DHEA play an important role in the development of hippocampus.

Animals↗

Actigraphic assessment of the preoperative hypnotic effects of brotizolam and zopiclone.

Brotizolam and zopiclone have a common ability to bind to the benzodiazepine recognition site and have been used as useful preoperative hypnotics. The aim of the present study was the quantitative evaluation of the preoperative hypnotic effects of brotizolam and zopiclone by actigraphy. Forty patients received brotizolam 0.25 mg (group B) or zopiclone 7.5 mg (group Z) in randomized manner at 21:30 on the night before surgery. Sleep and awake was identified by wrist activity measured with a motion-logger actigraph. Sleep time was assessed in total period from 22:00 to 6:00 and its 4 subdivided 2-hour periods (22:00-24:00, 24:00-2:00, 2:00-4:00, 4:00-6:00). The total sleep time in group B (448 +/- 23 min) was significantly longer than that in group Z (416 +/- 43 min). Group Z showed a significant reduction in sleep time in period 4 (4:00-6:00), compared with other periods, whereas group B did not show any difference among 4 periods. In comparison of each period between 2 groups, group B showed significant longer sleep time in period 4. An actigraphic assessment of sleep time has demonstrated the quantitative difference of the effects of brotizolam and zopiclone as preoperative hypnotics.

Adult↗

[An investigation of therapeutic effectiveness and the mechanism of oral appliance therapy on obstructive sleep apnea syndrome].

In order to investigate the effectiveness and the mechanism of action of oral appliances (OA) on obstructive sleep apnea syndrome (OSAS), a series of studies including overnight polysomnography, both ultrafast MRI and measurement of intraesophageal pressure during daytime naps and cephalometric analysis while awakening were performed on 19 OSAS patients before and during the treatment. In all cases, a significantly decreased apnea hypopnea index (AHI), shortened apnea duration, and a significant elevation in the lowest value of nocturnal arterial oxygen saturation, in comparison with the pretreatment values, were recognized during treatment with OA. The number of patients who responded to OA treatment, i.e., those whose AHI decreased by more than 50% of the pretreatment value, was 13 (68.4%). In cases with an AHI of 30 per hour of sleep or more before treatment, the number of arousals decreased and the percentage in stage 3 + 4 increased significantly during the use of OA. Cephalometric analysis revealed the anteroinferior advancement of the mandible, the anterosuperior movement of the hyoid bone and increase of upper airway area with OA in the cases studied. An MRI of the upper airway during sleep showed that glossopharyngeal obstruction disappeared with the use of OA in all cases, and velopharyngeal obstruction disappeared in nearly half of the cases. Moreover, the fluctuation of the intraesophageal pressure during sleep decreased significantly with OA. There were no differences in clinical background (e.g., age, body mass index, pretreatment value of AHI, and upper airway characteristics) in patients who AHI had decreased to less than 50% and those in whom it remained over 50%. These results confirmed the effectiveness of the treatment with OA. OA can be recommended for OSAS patients with not only glossopharyngeal obstruction, but also velopharyngeal obstruction, which is the most common cause of OSAS.

Adult↗

Age-specific effects of noradrenergic alpha-2 agonist clonidine on the development of amygdaloid kindling in developing rats.

The effects of clonidine on the development of amygdaloid kindling were studied in rats of various ages (14, 21, 28 and 70 postnatal days). Administration of clonidine (0.2, 0.5 mg/kg i.p.) caused a significant retardation of kindling development in the 28-day-old rats as well as in the adult rats, whereas, in the 14-day-old rats, the development of kindling was significantly facilitated by clonidine. No significant effect of clonidine was observed in the 21-day-old rats. These results indicate that in rats the effects of clonidine on the development of amygdaloid kindling vary during development.

Adrenergic alpha-Agonists↗

Development of computerized screening system for dementia and its preliminary field test.

The population of aged persons is increasing along with an extension of the average span of human life. Therefore, the number of persons who suffer from dementing disorders is also increasing. Because the various psychotic symptoms and behavioral problems are frequently observed in persons with dementia, the families taking care of such people require help to reduce their mental and physical load. Therefore, maintenance and enhancement of the social support system for aged persons are urgent issues. Early identification is important because immediate recognition of dementia people and appropriate follow up treatment can prevent the progress of the disease. Clinical interviews are one general method for detecting patients with dementing disorders, and the Hasegawa Dementia Scale is one of the most popular methods in Japan. The test takes about 10 min per person, but it requires a lot of time and burden for medical staff to screen patients with dementia from the increasing number of aged persons. Therefore, new methods for assessing cognitive functions are requested. A computerized assessment system was developed for dementia which is based on the Hasegawa Dementia Scale. This system was designed for aged persons with no previous computer experience to operate easily by making efficient use of multimedia. In this paper, the system and preliminary results of the field-test are reported.

Aged↗

Relationship between hypersomnia and respiratory disorder during sleep in Prader-Willi syndrome.

To assess whether hypersomnia in Prader-Willi syndrome (PWS) patients is related to the respiratory disorder during sleep (RDDS), we made a systematic evaluation regarding the relationship between the two disorders in three patients. All patients showed hypersomnia manifested as the long duration of night sleep and shortened sleep latencies of multiple sleep latency test. Although magnetic resonance imaging and laboratory studies revealed obstruction of the upper airway and mild increase of esophageal pressure during sleep, the number of other apneic episodes or awakenings was not as frequent. From the above results, we speculate that the mechanism of excessive daytime sleepiness in PWS is not caused by RDDS and quite resembles that of essential hypersomnia.

Adolescent↗

Treatment of periodic leg movement disorder and restless leg syndrome with talipexole.

In order to investigate the bedtime dose of talipexole, a D2 and alpha2 stimulant, on patients with periodic leg movement disorder (PLMD) and restless leg syndrome (RLS), we made a comparison of polysomnographic findings and subjective symptom ratings before and during 4 weeks of the treatment on five cases with RLS and PLMD. A significant decrease in both the frequencies of periodic leg movements and subjective symptom ratings and significant improvement of sleep composition were recognized during the treatment. We speculate that the combination of the agonistic action of D2 and alpha2 receptor with the drug might not only suppress PLMD and RLS but also improve sleep quality.

Azepines↗

Clinical efficacy and indication of acetazolamide treatment on sleep apnea syndrome.

The efficacy and indication of acetazolamide treatment on patients with sleep apnea syndrome (SAS) were discussed from assessing the changes of polysomnographic findings with the treatment in 75 SAS patients. For the patients as a whole, respiratory disorder variables improved significantly during the treatment. However, the number of acetazolamide treatment responders who showed a decrease of apnea hypopnea index (AHI) to 50% or less of the pretreatment value numbered only 34 (45.3%). The lower values of body mass index and AHI in the responder group indicated that monotherapy with acetazolamide is the treatment choice only for mild SAS cases without obesity. However, combined treatment with acetazolamide and uvulopalatopharyngoplasty was thought to be beneficial for severe cases.

Acetazolamide↗

Clinical efficacy of prosthetic mandibular advancement on obstructive sleep apnea syndrome.

In order to clarify the efficacy and indication of prosthetic mandibular advancement (PMA) on obstructive sleep apnea syndrome (OSAS), we made a comparison of both the polysomnographic findings and the upper airway configuration between before and during PMA on 19 OSAS patients. During PMA, there was a significant decreased apnea hypopnea index compared to before treatment. The changes in magnetic resonance imaging of the upper airway during sleep with PMA indicated that the treatment is regarded to be the first choice for OSAS patients with glossopharyngeal obstruction. In addition to that, the treatment might be considered for use in velopharyngeal obstruction.

Airway Resistance↗

Autonomic function in the early stage of panic disorder: power spectral analysis of heart rate variability.

Previous studies of autonomic nervous system (ANS) function in panic disorder (PD) patients have yielded conflicting results. We speculate that these differences might result from the variety of clinical stages of PD. In order to investigate this, we compared ANS activity in untreated patients in the early stage of PD with control subjects using power spectral analysis of electrocardiogram R-R intervals (PSR-R) in supine rest and during head-up tilt, which was performed according to the maximum entropy method (MEM). It recognizes two main components: high-frequency power (HF), which mainly reflects cardiac parasympathetic activity, and low-frequency power (LF), which reflects both cardiac sympathetic and parasympathetic activity. The patients with PD had significantly higher values for all components of PSR-R only in tilt position total power (TP), LF, and HF than did the control subjects (P<0.01, <0.01, <0.02, respectively). However, the LF/HF ratio which indicated sympathovagal balance did not differ significantly between the two groups in tilt position. Our findings suggest that patients with PD in the early stage of illness have co-activation of sympathetic and parasympathetic nervous systems, which might act to maintain a balance between the two autonomic systems.

Adult↗

Postpartum dissecting aneurysm of the superior cerebellar artery--case report.

A 37-year-old female with toxemia of pregnancy suffered sudden headache and loss of consciousness on the day following a cesarean delivery. Computed tomography revealed subarachnoid hemorrhage (SAH). Vertebral angiography revealed a fusiform dilatation near the origin of the right superior cerebellar artery (SCA) with distal luminal narrowing. She underwent surgery within 24 hours of the ictus. A SAH clot was carefully removed from the prepontine cistern, and subadventitial discoloration was seen in the wall of the right SCA just distal to the aneurysmal protuberance (rupture site). The dissecting aneurysm was treated with body clipping by directly clipping the rupture site and with additional wrapping of the proximal SCA, including the aneurysmal protuberance and discolored site. The postoperative clinical course was uneventful. Postoperative angiography revealed complete obliteration of the aneurysm and patency of the SCA. Therapeutic intervention should be considered for patients with ruptured dissecting aneurysm who present with recurrent SAH.

Adult↗

Plasma concentration of immunoreactive vascular endothelial growth factor and its relation to smoking.

We determined the plasma concentration of immunoreactive vascular endothelial growth factor (IR-VEGF) and searched for a relationship between it and the degree of microangiopathy. The plasma VEGF level was measured using an enzyme immunoassay in 110 non-insulin-dependent diabetes mellitus (NIDDM) patients with varying degrees of nephropathy or retinopathy (RP) and in 39 healthy controls and 30 nondiabetic patients for comparison. One fourth of the control subjects, 60% of whom were currently smokers, had plasma levels of IR-VEGF higher than the lower limit (15.6 pg/mL) of detection for this assay, whereas this was the case in half of the NIDDM patients. Plasma IR-VEGF was detectable in all patients with cerebral infarction, chronic renal failure, and severe infection, suggesting that tissue hypoxia might be a common cause for the elevation of plasma VEGF in these disorders. The prevalence of measurable plasma IR-VEGF levels increased in parallel with increases in the urinary albumin excretion rate ([UAER] 35.1% for UAER <30 mg/24 h, 54.8% for UAER 30 to 300 mg/24 h, and 61.3% for UAER >300 mg/24 h; P < .05 v UAER <30 mg/24 h). The mean measurable plasma concentration tended to increase with increasing UAER. However, there was no such correlation with the severity of RP. Smoking caused an acute increase of plasma IR-VEGF in only 22.6% (12 of 53) of the patients with a smoking habit. In conclusion, these findings suggest that circulating IR-VEGF may be linked to the progression of nephropathy, and smoking may facilitate this process by causing tissue hypoxia in susceptible patients.

Adult↗