Estimates of genetic relatedness among males in a polygynous wasp.

Cyclical oligogyny is considered to be the mechanism that is most likely to be responsible for stabilizing cooperation in polygynous, epiponine wasps, in which single-queen colonies produce new queens and multiple-queen colonies produce males. In contrast with the number of studies on relatedness among adult females, we know little about relatedness among males in polygynous epiponine wasps. We estimated worker and male relatedness in the Brazilian epiponine wasp Polybia paulista Ihering and found that colonies of P. paulista produced males when they contained multiple queens. Although average relatedness within males did not differ significantly from 0.5, the number of alleles observed suggests that there were more than one queen to produce males in each colony. Our data would be helpful to elucidate dynamics of the male production in a colony of epiponine wasps.

Effects of NMDA receptor-related agonists on learning and memory impairment in olfactory bulbectomized mice.

A significant impairment of learning and memory-related behavior was induced in mice on the 7th and 14th days after olfactory bulbectomy (OBX), as measured by a passive avoidance task. The involvement of the N-methyl-D-aspartate (NMDA) receptor ion-channel complex for learning and memory-related behavior impairment was examined by the intracerebroventricular administration of several NMDA receptor-related agonists and in combination with antagonists. The NMDA receptor agonist NMDA (1 ng/mouse) and the polyamine site agonist spermidine (1 micro g/mouse) improved learning and memory-related behavior impairment. In contrast, the glycine agonist D-cycloserine (0.2, 1 and 5 micro g/mouse) had no effect on learning and memory-related behavior impairment. The improved effects by NMDA and spermidine were reversed by the coadministration of D-APV, a competitive NMDA receptor antagonist, MK-801, an NMDA ion-channel blocker and ifenprodil, a polyamine site antagonist, respectively. These results suggest that the degeneration of NMDA receptors and polyamine sites in the NMDA receptor ion-channel complex may be involved in the OBX-induced impairment of learning and memory-related behavior.

Enhancement of 5-hydroxytryptamine-induced head-twitch response after olfactory bulbectomy.

5-Hydroxytryptamine(2A) receptor agonists evoke the head-twitch response in mice. The head-twitch response in olfactory bulbectomized mice elicited by the administration of 5-hydroxytryptamine (40 microgram/mouse, i.c.v.) was increased about threefold as compared with controls on the 14th day after the operation. The injection of ketanserin (1 mg/kg, i.p.), a 5-hydroxytryptamine(2A) receptor antagonist, inhibited this enhancement of 5-hydroxytryptamine-induced head-twitch response after olfactory bulbectomized. On the 14th day, the number of head-twitch response induced by 5-hydroxytryptophan (40, 80 and 160 mg/kg, i.p.), a precursor of 5-hydroxytryptamine, did not differ between olfactory bulbectomized and control mice. Monoamine oxidase-B activity in the forebrain of olfactory bulbectomized mice was higher than that in controls while monoamine oxidase-A activities were unchanged. The 5-hydroxytryptamine uptake into synaptosomes in the forebrain homogenates of olfactory bulbectomized mice was lower than that in controls. These findings indicate that olfactory bulbectomized causes the enhancement of head-twitch response by a supersensitivity of 5-hydroxytryptamine(2A) receptors in cerebral cortex derived from degeneration of neurons projecting from the olfactory bulb.

Antinociceptive effect following dietary-induced thiamine deficiency in mice: involvement of substance P and somatostatin.

We produced thiamine deficiency by treating mice with a thiamine deficient (TD) diet, but not with pyrithiamine, a thiamine antagonist. Twenty days after TD feeding, a significant antinociceptive effect was observed in the formalin test. A single injection of thiamine HCl (50 mg/kg, s.c.) on the 19th day after TD feeding (on the late TD stage) failed to reverse the antinociceptive effect, the muricide effect, and impairment of avoidance learning induced by TD feeding, as compared to pair-fed controls. These results indicate the possibility that the TD-induced antinociceptive effect may result from irreversible changes in the spinal and/or brain neurons. To clarify the involvement of substance P (SP) and somatostatin (SST) systems in the spinal cord, we examined the effect of intrathecal (i.t.) injections of these agonists on TD feeding-inducd elevation of pain threshold. I.t. injection of SP and SST elicited a behavioral response consisting of reciprocal hindlimb scratching, biting and/or licking of hindpaws. There was no significant difference in the behavioral response to SP between TD mice and PF mice on the 5th day after feeding. However, on the 10th and 20th day after TD feeding the response to SP was significantly increased compared with PF mice. This phenomenon was also observed with SST on the 20th day after TD feeding. These results indicate the possibility that TD feeding may produce an increased behavioral response to SP and SST through an enhanced sensitivity of neurokinin-1 and SST receptors in the spinal cord. Taken together, the antinociceptive effect following TD feeding may result from a decrease in spinal SP and SST contents.

Characteristics of depressive behavior induced by feeding thiamine-deficient diet in mice.

We produced thiamine-deficient (TD) mice by TD diet treatment. The growth curve of mice on TD feeding was sharply increased until on the 10th day and subsequently the body weight gradually decreased. The mortality rate in mice was about 67% on the 30th day after the start of TD feeding. We performed the forced swimming test on the 10th and 20th day after the start of TD feeding. The duration of immobility in the forced swimming test was increased on the 20th day of TD feeding. Locomotor activity and motor co-ordination between the pair-fed control group and TD group on the 20th day of TD feeding were not significantly changed. Only a single injection of thiamine HCI (50 mg/kg, s.c.) on the 10th day after the start of a TD diet shortened the increased duration of immobility in the forced swimming test on the 20th day after the start of TD feeding. Whereas these reversal effects of thiamine treatment on the 20th day were not found when the treatment was given on the 19th day after the start of a TD diet. On the 20th day after the start of TD feeding, the increased duration of immobility time induced by TD was shortened by chronic administration of the tricyclic antidepressant imipramine (10 mg/kg, i.p.). These results suggested that behavioral changes in the forced swimming test might be involved in the degeneration of serotonergic and noradrenergic neurons.

Antinociceptive action of amlodipine blocking N-type Ca2+ channels at the primary afferent neurons in mice.

We investigated the antinociceptive action of amlodipine, a dihydropyridine derivative, which acts on both L- and N-type voltage-dependent Ca2+ channels (VDCCs), in mice. Intrathecal injection of amlodipine (300 nmol/kg) significantly shortened the licking time in the late phase of a formalin test, while no effect was found with another dihydropyridine derivative, nicardipine (300 nmol/kg). Cilnidipine and omega-conotoxin GVIA also showed marked analgesic effects under the same experimental conditions. Transcripts of alpha1A, alpha1B, alpha1E, alpha1F, alpha1H, beta3, and beta4 subunits were detected by polymerase-chain reaction (PCR) in the dorsal root ganglion, suggesting the existence of a variety of voltage-dependent Ca2+ channels. Electrophysiological experiments showed that amlodipine and cilnidipine inhibit N-type currents in the dorsal root ganglion cells. These results suggest that amlodipine, cilnidipine, and omega-conotoxin GVIA exert their antinociceptive actions by blocking N-type Ca2+ channels in the primary nociceptive afferent fibers. Blocking of the Ca2+ channels results in attenuation of synaptic transmission of nociceptive neurons. Furthermore, it is suggested that some N-type Ca2+ channel blockers might have therapeutic potential as analgesics when applied directly into the subarachnoidal space.

Pain threshold, learning and formation of brain edema in mice lacking the angiotensin II type 2 receptor.

The main biological role of angiotensin II type 2 receptor (AT2) has not been established. We made use of targeted disruption of the mouse AT2 gene to examine the functional role of the AT2 receptor in the central nervous system (CNS). We have previously shown that AT2-deficient mice displayed anxiety-like behavior in comparisons with wild-type mice. In the present study, we analyzed the pain threshold, learning behavior and brain edema formation using the tail-flick test, the tail-pinch test, the passive avoidance task and cold injury, respectively. In the passive avoidance task and cold injury, no differences were found between wild-type mice and AT2-deficient mice. In contrast, the pain threshold was significantly lower in AT2-deficient mice, compared with findings in wild-type mice. The immunohistochemical distribution of beta-endorphin in the brain was analyzed quantitatively in AT2-deficient mice and wild-type mice, using microphotometry. The fluorescence intensity of beta-endorphin in the arcuate nucleus of the medial basal hypothalamus (ARC) was significantly lower in AT2-deficient mice, compared with findings in wild-type mice. We found that the AT2 receptor does not influence learning behavior and brain edema formation. As AT2-deficient mice have increased sensitivity to pain and decreased levels of brain beta-endorphin, AT2 receptors may perhaps mediate regulation of the pain threshold.

Supplementary administration of artificial bright light and melatonin as potent treatment for disorganized circadian rest-activity and dysfunctional autonomic and neuroendocrine systems in institutionalized demented elderly persons.

Increased daytime napping, early morning awakening, frequent nocturnal sleep interruptions, and lowered amplitude and phase advance of the circadian sleep-wake rhythm are characteristic features of sleep-waking and chronobiological changes associated with aging. Especially in elderly patients with dementia, severely fragmented sleep-waking patterns are observed frequently and are associated with disorganized circadian rhythm of various physiological functions. Functional and/or organic deterioration of the suprachiasmatic nucleus (SCN), decreased exposure to time cues such as insufficient social interaction and reduced environmental light, lowered sensitivity of sensory organs to time cues, and reduced ability of peripheral effector organs to express circadian rhythms may cause these chronobiological changes. In many cases of dementia, the usual treatments for insomnia do not work well, and the development of an effective therapy is an important concern for health care practitioner and researchers. Recent therapeutical trials of supplementary administration of artificial bright light and the pineal hormone melatonin, a potent synchronizer for mammalian circadian rhythm, have indicated that these treatments are useful tools for demented elderly insomniacs. Both bright light and melatonin simultaneously ameliorate disorganized thermoregulatory and neuroendocrine systems associated with disrupted sleep-waking times, suggesting a new, potent therapeutic means for insomnia in the demented elderly. Future studies should address the most effective therapeutic design and the most suitable types of symptoms for treatment and investigate the use of these tools in preventive applications in persons in early stages of dementia.

Antinociceptive effect of cilnidipine, a novel N-type calcium channel antagonist.

We investigated the antinociceptic effects of cilnidipine, a dihydropyridine derivative which acts on both L- and N-type voltage-dependent calcium channels, in mice. Intrathecally injected cilnidipine showed significant analgesic effect in formalin test. Cilnidipine significantly suppressed N-type currents in dorsal root ganglion (DRG) cells. Our findings apparently support the idea that cilnidipine attenuates synaptic neurotransmission by inhibiting N-type calcium channels in DRG neurons.

Bar Dissolution in Prolate Halos.

The time evolution of barred structures is examined under the influence of the external forces exerted by a spherical halo and by prolate halos. In particular, galaxy disks are placed in the plane including the major axis of prolate halos, whose configuration is often found in cosmological simulations. N-body disks in fixed external halo fields are simulated, so that bars are formed via dynamical instability. In the subsequent evolution, the bars in prolate halos dissolve gradually with time, while the bar pattern in a spherical halo remains almost unchanged to the end of the simulation. The decay times of the bars suggest that they can be destroyed in a time smaller than a Hubble time. Our results indicate that this dissolution process could occur in real barred galaxies, if they are surrounded by massive dark prolate halos, and the configuration adopted here is not unusual from the viewpoint of galaxy formation. For a prolate halo model, an additional simulation that is restricted to two-dimensional in-plane motions has also ended up with similar bar dissolution. This means that the vertical motions of disk stars do not play an essential role in the bar dissolution demonstrated here.

Immunohistochemical estimation of brain choline acetyltransferase and somatostatin related to the impairment of avoidance learning induced by thiamine deficiency.

We have found that thiamine-deficient (TD) rats show significant impairment of avoidance learning on the 25th day after the start of TD diet, as measured by passive-avoidance task. Administration of physostigmine (0.1 mg/kg, i.p.) from the 14th day after the start of TD diet improved the impairment of avoidance learning to the pair-fed (PF) control level by the 25th day. However, the recovery effect of physostigmine did not occur on the 25th day when the treatment was begun on the 21st day. To ascertain the correlation between the cholinergic neuronal function in rat brain and the avoidance learning impairment induced by TD, the immunohistochemical distribution of brain choline acetyltransferase (ChAT) was determined by fluorescence intensity using two-dimensional microphotometry. The intensity of the ChAT fluorescence started to decrease in the cortex and hippocampus on the 14th day and showed a marked decrease in the cortex, hippocampus and thalamus on the 25th day of TD feeding in comparison with PF controls. The intensity of the somatostatin (SST) fluorescence was unchanged on the 14th day of TD feeding, but on the 25th day, SST was significantly decreased in comparison with PF controls. Furthermore, physostigmine treatment from 14th day after the start of TD diet reversed SST fluorescence intensity to the control level by the 25th day. These results suggest that the impairment of avoidance learning induced by TD may involve not only cholinergic but also somatostatinergic systems.

Primary squamous cell carcinoma of accessory parotid gland duct epithelium: report of a case.

A rare case of primary squamous cell carcinoma surrounding Stensen's duct in a 75-year-old man is presented. The tumor was a relatively well-defined, hard, subcutaneous mass, measuring 18 x 14 x 9 mm and situated in the right cheek. Microscopic examination of an excisional biopsy specimen revealed tumor cells showing squamous differentiation, a papillary growth pattern, and ductal structures with comedo necrosis. Immunohistochemical studies showed positive reactivity for KL-1 (cytokeratin, monoclonal), epithelial membrane antigen, and carcinoembryonic antigen in some tumor cells. The origin of the tumor was thought to be the accessory parotid gland duct epithelium.

Different manifestations of circadian rhythms in senile dementia of Alzheimer's type and multi-infarct dementia.

Using an actigraph and a long-term body temperature (BT) monitoring system, we simultaneously monitored rest-activity (R-A) and BT rhythms in patients with senile dementia of Alzheimer's type (SDAT; n = 20) or multi-infarct dementia (MID; n = 21) for 5-7 consecutive days. The SDAT group exhibited a well-organized BT rhythm with significantly higher amplitude compared with the MID group. The SDAT group also showed significant positive correlation between the total daily activity as well as percentage of nighttime activity and the degree of dementia, while no such tendency was observed in the MID group. The different properties of the biological rhythm disorders among the SDAT and MID groups possibly underlie their sleep and behavioral disorders.

Favorable effect of transcranial electrostimulation on behavior disorders in elderly patients with dementia: a double-blind study.

The efficacy of transcranial electrostimulation for sleep-wake and behavior disorders in elderly patients with dementia was tested in a double-blind study. The subjects were 27 inpatients with multi-infarct dementia (12 males and 15 females, aged 58-86). They were randomly divided into two groups: active treatment (n = 14) and placebo treatment (n = 13). For electrostimulation, a device (HESS-100) was used which delivered repetitive rectangular electric pulses of 6-8 V at increasing frequencies from 6 to 80 Hz, each pulse lasting 0.2 ms and with a root mean square value of 256-530 microA. Electrostimulation was performed for 20 minutes from 10:00 h every morning. The active or placebo treatment was performed for 2 weeks in each group. The electrostimulation was significantly effective in behavior disorders such as wandering or nocturnal delirium, and decreased motivation during the daytime. It was also effective in improving night sleep. Electroencephalograms confirmed increased vigilance levels in the daytime both during and after the treatment.

On the EEG component waves of multi-infarct dementia seniles.

Component waves of EEGs led from the F3-A1, C3-A1, O1-A1, and O2-A2 scalp regions of 24 multi-infarct dementia seniles (MID) patients (ages 58 to 85 years, average 73.3 years) and eight to 19 normal, healthy, adult (NA) subjects were obtained by autoregressive component analysis. Some differences in the component waves were demonstrated between the two groups of subjects. (1) The characteristics of the EEG component waves, including the natural, damping, and resonance frequencies, their power, regularity, etc. were determined, and compared between MID patients and NA subjects. (2) No significant difference was found between male and female patients in the occurrence rate of 11 types of component waves. (3) On the average, the alpha wave frequency was lower in MID patients. (4). Slow alpha waves (7.5 to 9.4 Hz) of MID patients were superior to those of NA subjects, whereas typical alpha waves (9.5 to 11.4 Hz) were inferior to those of NA subjects. (5) The power of alpha waves in the F3-A1 and C3-A1 regions of MID patients was superior to that of NA subjects, whereas the result was reversed in the O1-A1 and O2-A2 regions. However, there was less regularity of alpha waves in all regions among MID patients. (6) The theta wave frequency in all regions was higher in MID patients than in NA subjects. (7) Both the power and regularity of theta waves of MID patients were superior to those of NA subjects in all regions. (8) The average number of delta waves that appeared in the O1-A1 and O2-A2 regions was larger in MID patients than in NA subjects. EEG were led from the F3-A1, C3-A1, O1-A1, and O2-A2 scalp regions of multi-infarct dementia seniles (MID) patients, who had sleep disorders, such as reversed day-time sleep patterns or irregular sleep-wake patterns, frequently accompanied by behavior disorders, such as wandering, violent behavior, and/or delirium. Examination by the method of EEG pattern discrimination revealed some differences in EEG component waves in comparison with normal, healthy, adult (NA) subjects.

[Rest-activity and body-temperature rhythm disorders in elderly patients with dementia--senile dementia of Alzheimer's type and multi-infarct dementia].

We simultaneously monitored rest-activity and body temperature (BT) rhythm in demented patients with sleep and behavior disorders using ambulatory wrist-worn actigraph and long-term monitoring system for 5-7 consecutive days. Subjects consisted of 19 patients with senile dementia of Alzheimer's type (SDAT) (M/F = 7/12, mean age = 71.7 years), 16 patients with multi-infarct dementia (MID) (M/F = 9/7, mean age = 75.2 years) and 9 normal controls (M/F = 4/5, mean age = 70.4 years). Both dementia groups showed a significant increase in percentage of nighttime activity. In the SDAT group, a significant positive correlation between the degree of dementia and total activity was observed, but not observed in the MID group. A significant high amplitude of BT rhythm was observed in the SDAT group comparing that in the MID or the control group. These findings indicate that the SDAT patients had a disrupted rest-activity rhythm with the severity of intellectual deterioration and increased night activity, while the circadian BT rhythm was remarkably well preserved, i.e. there was a dissociation between rest-activity and BT rhythms in the SDAT group. On the other hand, the disruption of the rest-activity and BT rhythm in the MID patients was characterized by a concomitant decrease of amplitude, which seems to have no relation with the severity of dementia. Different mechanisms could be involved in characteristic disruption of the circadian rhythms in the 2 dementia groups.

[Influence of the yellow-tinted intraocular lens on spectral sensitivity].

One of the complaints of patients with aphakic eyes or pseudophakic eyes implanted with UV or non-UV intraocular lenses (IOLs) is chromatopsia. To determine the extent of color distortion, we measured the spectral sensitivity curve of normal subjects with visual acuity above 1.0 with correction, if any, including subjects implanted with the yellow-tinted IOL (UVCY IOL: HOYA Co.). We found that color sensitivity in the blue range (400-440 nm) declined rapidly with subjects age. We drew a regression line plotting age against sensitivity for 66 normal subjects. Sensitivity for pseudophakic eyes implanted with UVCY and UV IOLs at 400 nm corresponds to that of subjects in their early 20's. That of pseudophakic eyes implanted with non-UV IOLs and aphakic eyes corresponded to that of infants. In summary, compared to UV IOL and non-UV IOLs, the UVCY IOL was found to best approximate the color sensitivity of healthy eyes.

Morning bright light therapy for sleep and behavior disorders in elderly patients with dementia.

Fourteen inpatients with dementia showing sleep and behavior disorders (average age = 75 years), and 10 control elderly people (average age = 75 years) were carefully observed for 2 months. Four weeks of morning light therapy markedly improved sleep and behavior disorders in the dementia group. The measurement of sleep time and the serum melatonin values suggests that sleep and behavior disorders in the dementia group are related to decreases in the amplitude of the sleep-wake rhythm and decreases in the levels of melatonin secretions. Morning light therapy significantly increased total and nocturnal sleep time and significantly decreased daytime sleep time. These results indicate that morning bright light is a powerful synchronizer that can normalize disturbed sleep and substantially reduce the frequency of behavior disorders in elderly people with dementia.

Circadian rhythm disorders in sleep-waking and body temperature in elderly patients with dementia and their treatment.

Circadian rhythms in elderly patients with severe dementia and behavioral disorders such as wandering, agitation and/or delirium were examined. The subjects consisted of 24 patients with dementia (5 with senile dementia of Alzheimer's type and 19 with multi-infarct dementia), aged 56-89 (means = 75.5 +/- 8.7) and 8 control patients without dementia or with dementia of slight degree, aged 65-81 (means = 75 +/- 5.4). The sleep-wake state of the patients was judged every hour by nurses over periods of 1-4 mo and recorded in the form of a sleep diary. Oral temperature was recorded for 4-7 consecutive days. For the treatment of sleep-wake rhythm disorders, social interaction with nurses was encouraged in addition to drug therapy. The patients showed various types of sleep-wake disorders such as reversed day-night rhythm or irregular sleep-wake rhythm corresponding to a decreased amplitude of the sleep-wake rhythm. Circadian rhythm of oral temperature was irregularly disturbed in 59.0% of the patients in the dementia group and in only 12.5% of the patients in the control group. The effects of treatment by enforcement of social interaction with nurses was effective in reducing behavioral problems and sleep-wake rhythm disorder in 30.0% of the patients tested. However, body temperature rhythm disorganization remained after the treatment. These observations indicate that behavioral disorders such as delirium, agitation or wandering in patients with severe dementia might be closely related to disrupted biological rhythms of sleep-waking and the autonomic system (body temperature).