Differential effects of chronic stress in young-adult and old female mice: cognitive-behavioral manifestations and neurobiological correlates.

Stress-related psychopathology is highly prevalent among elderly individuals and is associated with detrimental effects on mood, appetite and cognition. Conversely, under certain circumstances repeated mild-to-moderate stressors have been shown to enhance cognitive performance in rodents and exert stress-inoculating effects in humans. As most stress-related favorable outcomes have been reported in adolescence and young-adulthood, this apparent disparity could result from fundamental differences in how aging organisms respond to stress. Furthermore, given prominent age-related alterations in sex hormones, the effect of chronic stress in aging females remains a highly relevant yet little studied issue. In the present study, female C57BL/6 mice aged 3 (young-adult) and 20-23 (old) months were subjected to 8 weeks of chronic unpredictable stress (CUS). Behavioral outcomes were measured during the last 3 weeks of the CUS protocol, followed by brain dissection for histological and molecular end points. We found that in young-adult female mice, CUS resulted in decreased anxiety-like behavior and enhanced cognitive performance, whereas in old female mice it led to weight loss, dysregulated locomotion and memory impairment. These phenotypes were paralleled by differential changes in the expression of hypothalamic insulin and melanocortin-4 receptors and were consistent with an age-dependent reduction in the dynamic range of stress-related changes in the hippocampal transcriptome. Supported by an integrated microRNA (miRNA)-mRNA expression analysis, the present study proposes that, when confronted with ongoing stress, neuroprotective mechanisms involving the upregulation of neurogenesis, Wnt signaling and miR-375 can be harnessed more effectively during young-adulthood. Conversely, we suggest that aging alters the pattern of immune activation elicited by stress. Ultimately, interventions that modulate these processes could reduce the burden of stress-related psychopathology in late life.

[Development of factor VIII inhibitor in three non-hemophiliac patients].

Infrequently, inhibitors against factor VIII can develop in non-hemophiliac patients and cause serious bleeding. In the last year, we have experienced 3 non-hemophiliac patients who developed factor VIII inhibitors. Here, we describe the clinical courses of the three patients and the characteristics of the inhibitors. Case 1: A 69-year-old man underwent a partial gastrectomy because of early gastric cancer, and one month later developed signs of a bleeding tendency such as hematemesis, tarry stools and intramuscular hemorrhage. Blood coagulation tests revealed prolongation of the activated partial thromboplastin time (aPTT), which had been normal on admission. Case 2: A 78-year-old woman with no previous disease history developed generalized subcutaneous purpura. Blood coagulation tests performed on admission revealed a prolonged aPTT. Case 3: A 30-year-old man was admitted to an emergency hospital because of left intrapleural hemorrhage and liver injury caused by a traffic accident. Two months later, a hematoma developed at the site of drainage in the left chest, and blood coagulation tests revealed prolongation of the aPTT, which had been normal on admission. Plasma factor VIII procoagulant activities in cases 1, 2 and 3 were 3%, 1% and 5%, respectively. The respective factor VIII inhibitor titers were 78, 870 and 0.5 Bethesda units/ml. The immunoglobulin class and subclass of the inhibitors examined by an ELISA method were: case 1, IgG1 and 4; case 2, IgG2 and 4 (dominant); case 3, IgG4. In cases 1 and 3, the patients recovered after glucocorticoid therapy, but in case 2 the patient died of intraperitoneal hemorrhage despite receiving two courses of methylprednisolone pulse therapy. The above clinical experience suggests that patients, who develop high titers of inhibitors may be refractory to ordinary immunosuppressive therapy, and therefore more aggressive therapy such as plasma exchange and/or bypass therapy using activated prothrombin complex concentrates or an activated factor VII preparation should be considered.

Saccadic tracking of a light grey target in the mantis, Tenodera aridifolia.

I presented a horizontally moving square on a computer display to the mantis, Tenodera aridifolia, and examined the effects of target brightness and velocity, and background brightness on its tracking behavior. The mantis tracked a light grey square with more saccadic head movements than a black square, although these squares moved on a homogeneous background. The amplitude of saccades was larger when the light grey square moved at a lower velocity. The background brightness had little effect on the type (smooth or saccadic) of tracking behavior. These results suggest that the saccadic tracking of light grey objects on a homogeneous background may not be caused by low contrast, i.e., the difficulty in discriminating the object from the background. The possible biological significance of saccadic tracking on a homogenous background is discussed.

Serovar, pathogenicity and antimicrobial susceptibility of erysipelothrix rhusiopathiae isolates from farmed wild boars (Sus scrofa) affected with septicemic erysipelas in Japan.

Six strains of Erysipelothrix rhusiopathiae were isolated from farmed wild boars with acute septicemic erysipelas during the period from 1983 to 1998 in Japan. All isolates belonged to serovar 1a or 2 (predominant serovars in swine). The 50 per cent lethal dose values of those isolates ranged from 10(1.3)to 10(6.2)colony forming units in mice. In swine, all isolates were virulent, capable of inducing localized or generalized urticarial lesions after intradermal inoculation. All of the isolates were resistant to oxytetracycline and/or dihydrostreptomycin. These observations suggest that E. rhusiopathiae strains isolated from wild boars may have aetiological significance in swine erysipelas.

Age-associated changes in the dopamine synthesis as determined by GTP cyclohydrolase I inhibitor in the brain of senescence-accelerated mouse-prone inbred strains (SAMP8).

Our objective in this study was to elucidate the mechanism underlying the decrease in dopamine (DA) levels in the brain with ageing We administered 2,4-diamino-6-hydroxypyrimidine (DAHP), an inhibitor of GTP cyclohydrolase I to senescence-accelerated mouse-prones (SAMP8), to inhibit DA and serotonin syntheses, and following immunohistochemical staining, analyzed the immunoreactive intensities (IR-Is) for DA in the nigrostriatal dopaminergic neurons by microphotometry. The DA-IR-Is in the substantia nigra pars compacta and neostriatum of young mice (2 months old) reached a minimal value 3 h after DAHP administration and returned to the control value 12 h after the administration. However, in aged mice (10 months old), the minimal value was reached 6 h after the administration and the value remained at approximately 70 and 80% of the control value at 24 and 72 h, respectively, after DAHP administration. The results suggest that DA turnover is lower in aged mice than in young mice.

Clinical, pathological and mineralogical features in two autopsy cases of workers exposed to agalmatolite dust.

An agalmatolite miner and processor showed large shadows at the bilateral hila accompanied by surrounding emphysematous changes and irregular shadows on chest X-ray films. Chest CT scans were characterized by a mixture of tiny irregular structures and small round opacities. Histopathological examination revealed massive fibrosis, which corresponded to large shadows, but only a small number of typical silicotic nodules, indicating mixed dust pneumoconiosis. Mineralogical examination of the autopsy lungs showed quartz, pyrophyllite, mica, and kaolinite. Quartz accounted for 70% of the amount of all mineral dust in both patients, but pyrophyllite accounted for 10.8% and 14.4%. The pulmonary mineral dust composition in the two patients was well consistent with the mineral composition of the raw clays in the agalmatolite mine. In the two patients, chest X-ray findings and histopathological findings of the lungs also suggested agalmatolite pneumoconiosis, which was confirmed by mineral analysis of the lungs.

In vivo evaluation of a novel alginate dressing.

Alginate dressings are currently used in the management of epidermal and dermal wounds, and provide a moist environment that leads to rapid granulation and reepithelialization. However, a cytotoxic effect on proliferation of fibroblasts and residual material with inflammation in healing wounds have been reported recently. We have developed a new alginate dressing (AGA-100), which does not have an inhibitory effect on proliferation of fibroblasts. The purpose of this study was to evaluate the new alginate dressing with respect to wound healing in full- and partial-thickness pig wounds and with respect to biodegradation following implantation into rabbit muscle. Kaltostat and Sorbsan, both well-established commercial dressings, were used as control. The closure rate of full-thickness wounds treated with AGA-100 was significantly higher on day 15 compared with that with Kaltostat and Sorbsan. Reepithelialization rate of partial-thickness wounds treated with Sorbsan was statistically significantly lower on day 3 than those with the other two dressings. As to dressing debris remained in the healing wound, a large amount of foreign debris was noted in all the full-thickness wounds treated with Kaltostat or Sorbsan, while only about one-third of wounds treated with AGA-100 showed a little dressing debris. AGA-100 implanted into the muscle of rabbits was bioresorbed completely within 3 months. Therefore, dressing residue in AGA-100-treated full-thickness wounds might be fully absorbed in a few months. In conclusion, it is shown that our newly developed AGA-100 possesses superior properties compared with typical alginate dressings.

Eustachian tube cartilage and medial movement of lateral pharyngeal wall on phonation.

Several authors have demonstrated the importance of medial movement of the lateral pharyngeal wall in velopharyngeal closure upon phonation. However, it remains controversial what muscle is responsible for lateral pharyngeal wall movement and where is the main site of this movement. The purpose of this study was to address the above two unanswered questions. In 22 subjects (12 normal volunteers, 10 patients with cleft palate), lateral pharyngeal wall movement upon phonation was evaluated by using rapid magnetic resonance imaging (MRI). Before rapid MRI, their lateral pharyngeal wall movements were classified into three groups: the poor, moderate, and good, according to the findings of nasopharyngoscopy. Inward displacement of the eustachian tube cartilages upon phonation, which was quantified as distance ratio in the transverse plane of MR images, was compared with nasopharyngoscopic findings. In addition, the level of lateral pharyngeal wall movement was observed in the plane 5 mm lateral to the mid-sagittal plane of MR images. Inward displacement of the eustachian tube cartilage in the transverse plane of MR images was coincident with medial movement of lateral pharyngeal wall observed by nasopharyngoscopy in all 22 subjects. By using one-way analysis of variance, a statistically significant correlation was found between nasopharyngoscopic classification and distance ratio. The sagittal plane of MR images revealed that the main site of movement occurred at the level of the hard palate and above. It is concluded that medial movement of the lateral pharyngeal wall consists of inward displacement of the eustachian tube cartilage, which is caused by contraction of the levator veli palatini muscle, and that the primary site of this movement is at the level of the hard palate and above, where the eustachian tube, but not the superior constrictor muscle, exists.

Effect of acyclovir on bronchoconstriction and urinary leukotriene E4 excretion in aspirin-induced asthma.

BACKGROUND: Acyclovir (9-[2-hydroxyethoxymethyl] guanine), an inhibitor of the DNA polymerase of the herpes virus, has been reported to exhibit pharmacologic activity other than antiviral activity, including antiasthmatic effects. OBJECTIVE: This study was designed to investigate the protective effect of acyclovir on airway responsiveness to the sulpyrine provocation test and to investigate whether this protective activity is associated with a reduction in aspirin-induced excretion of urinary leukotriene E4 (u-LTE4 ), a marker of cysteinyl leukotriene (LT) overproduction that participates in the pathogenesis of aspirin-induced asthma. METHODS: We assessed the effects of pretreatment with acyclovir on bronchoconstriction precipitated by inhalation of sulpyrine in 16 adult patients with mild or moderate aspirin-induced asthma; those who were in stable clinical condition and were hyperresponsive to the sulpyrine provocation test were allocated to this study. A double-blind, randomized, cross-over design was used. u-LTE4 was measured by a combined reverse-phase HPLC enzyme immunoassay. RESULTS: Acyclovir protects against aspirin-induced attacks of asthma through mechanisms unrelated to its bronchodilator property but related to the improvement of bronchial hypersensitivity to sulpyrine; protection was nearly complete in all patients (P <.0001). By contrast, after acyclovir, the maximum level of u-LTE4 in patients was significantly lower than that in control subjects (P <. 01). CONCLUSION: Our results suggest that acyclovir is not only an antiviral drug but also an inhibitor of analgesic-induced bronchoconstriction, probably acting by inhibiting the release of cysteinyl LTs.

Bronchial hyperresponsiveness, hypersensitivity to analgesics and urinary leukotriene E4 excretion in patients with aspirin-intolerant asthma.

This study was designed to investigate the protective effect of cromolyn sodium on airway sensitivity to sulpyrine, and bronchial responsiveness to methacholine, and to investigate whether this protective activity is associated with reduction in aspirin-induced excretion of urinary leukotriene E4 (u-LTE4), a marker of the cysteinyl LT overproduction that participates in the pathogenesis of aspirin-induced asthma. We assessed the effects of pretreatment with cromolyn sodium on bronchoconstriction precipitated by inhalation of methacholine and sulpyrine in 16 adult patients with mild or moderate aspirin-intolerant asthma; those who were in stable clinical condition and were hypersensitive to a sulpyrine provocation test were included in this study. A double-blind, randomized, crossover design was used. u-LTE4 was measured using combined reverse-phase high-performance liquid chromatography enzyme immunoassay. Cromolyn sodium protected against analgesic-induced bronchoconstriction through mechanisms that are not related to its bronchodilator property, but to the improvement of both bronchial hyperresponsiveness and hypersensitivity to analgesics (p<0.01 and p<0.001). Although excretion of u-LTE4 did not increase after the methacholine provocation test, it significantly increased after sulpyrine provocation (p<0.01). Furthermore, after pretreatment with cromolyn sodium, the maximum level of u-LTE4 after the sulpyrine provocation test was significantly lower than in controls (p<0.01). These results support the hypothesis that cysteinyl LT is one of the most important components in the pathogenesis of aspirin-intolerant asthma. Cromolyn sodium improves both hypersensitivity to analgesics, and bronchial hyperresponsiveness in aspirin-intolerant asthma.

Evaluation of a novel alginate gel dressing: cytotoxicity to fibroblasts in vitro and foreign-body reaction in pig skin in vivo.

Calcium alginate dressings have beneficial effects on wound healing by providing a moist wound environment. However, cytotoxicity and the nonbiodegradable nature of calcium alginate dressings induce unresolved chronic foreign-body reaction. In this study, a novel freeze-dried alginate gel dressing (AGA-100) low in calcium ions was evaluated for cytotoxicity to L929 cells in vitro and in full-thickness pig wounds in vivo. Cytotoxicity testing on L929 cells showed the cytocompatibility of AGA-100 extracts, while extracts from Kaltostat, a well-established alginate dressing, induced cytopathic effects. In an in vivo study using pigskin, AGA-100, Kaltostat, and gauze were applied on 1-in-diameter circular full-thickness wounds on the back of pigs and the time course of wound closure was evaluated. Kaltostat and gauze dressings were used as controls. For histologic evaluation, wound tissue was harvested on day 18. AGA-100-treated wounds showed rapid wound closure compared to control wounds on day 15. Foreign-body reaction was marked in Kaltostat- and gauze-treated wounds, and differed significantly from AGA-100-treated wounds. Based on these data, AGA-100 could reduce the cytotoxicity to fibroblasts and foreign-body reaction that have been observed with currently available calcium alginate dressings; it was also found to be useful as an alginate dressing.

Immunohistochemical colocalization of GTP cyclohydrolase I in the nigrostriatal system with tyrosine hydroxylase.

Immunohistochemical colocalization of GTP cyclohydrolase I (GCH) in the mouse nigrostriatal system with tyrosine hydroxylase or aromatic L-amino acid decarboxylase in the somata and terminals of GCH-positive catecholaminergic neurons are proved for the first time by a double-labeling immunofluorescence method with a confocal laser-scanning microscope. GCH-immunoreactive somata in the mouse substantia nigra have synaptic contacts with monoaminergic and non-monoaminergic terminals.

Nonpathological focal enhancements on spiral CT hepatic angiography.

BACKGROUND: To assess the frequency and characteristics of nonpathological focal enhancements seen on spiral computed tomographic (CT) hepatic angiography (CTA). METHODS: Spiral CTA and spiral CT arterial portography (CTAP) were performed in 31 patients with suspected liver malignancy prior to potential liver resection. The CTA images were retrospectively reviewed for focal enhancements by two radiologists. After determining nonpathological focal enhancements on CTA images based on the other radiographic tests, surgical exploration including intraoperative sonography, follow-up imagings, the frequency, size, site, and shape of nonpathological focal enhancements with CTA were assessed. RESULTS: Thirty-six nonpathological focal enhancements with CTA from 4 to 23 (mean = 11. 4) mm were seen in 14 (45.2%) of 31 patients. Thirteen (36.1%) of 36 nonpathological focal enhancements with CTA were not depicted with CTAP. Nonpathological focal enhancements with CTA were frequent in Couinaud segments III (27.8%), V (22.2%), and VI (19.4%). Twenty-three (63.9%) of 36 nonpathological focal enhancements were located in the edge of the liver. Shapes of 36 nonpathological focal enhancements with CTA included circular (n = 16), worm (n = 7), irregular (n = 6), dot (n = 6), and wedge (n = 1). CONCLUSION: In nearly half of patients, spiral CTA shows various shapes of small nonpathological focal enhancements more frequently in the liver edge.

Demonstration of false-negative findings on CT hepatic angiography.

False-negative findings on CT angiography (CTA) in two patients with hepatocellular carcinoma (HCC) were demonstrated. CTA images of one patient with an aberrant left hepatic artery branching from the left gastric artery and another patient whose right hepatic artery was occluded owing to an unknown cause failed to demonstrate HCCs. This report suggests one of the diagnostic pitfalls of CTA for diagnosis of liver tumors.

Renal pelvic and ureteral carcinoma with huge hydronephrosis: US, CT, and MR findings.

A 78-year-old man presented huge hydronephrosis with a calculus in the left kidney, and underwent left nephroureterectomy under the diagnosis of renal pelvic and ureteral tumor. Histological examination disclosed renal pelvic and ureteral tumors featuring mixed histologic types of carcinoma. Magnetic resonance (MR) imaging was superior to computed tomography (CT) in its complete, detailed demonstration of the renal pelvic lesions. The imaging characteristics of CT, MR imaging, ultrasonography, and retrograde ureterography were discussed in the report.

Velopharyngeal closure and the longus capitis muscle.

The dynamic mechanism of velopharyngeal function not only in normal individuals but also in patients with velopharyngeal insufficiency, which is mainly related to cleft palate, has been the subject of considerable interest and controversy. Recently, in order to clarify velopharyngeal movement in the valvular action on phonation we examined dynamic MR images of this area taken in the transverse plane in parallel with the muscle sling of levator veli palatini. In cases in whom the closure pattern in that plane is circular, detailed observation revealed a very interesting result; that is, the longus capitis muscle, one of the group of anterior vertebral muscles, is directly involved in velopharyngeal valving function. It has not previously been reported that the longus capitis muscle acts as one of the velopharyngeal closure muscles, in addition to levator veli palatini. The present study demonstrated that contraction of the muscle contributed to velopharyngeal closure by forward movement of the pharyngeal wall.