Effect of nanoparticles on the male reproductive system of mice.

The effects of nanoparticles toward on the male reproductive system of mice were investigated. Three sizes (14, 56 and 95 nm) of carbon black nanoparticles were intratracheally administered (0.1 mg/mouse for 10 times every week) to ICR male mice to investigate their adverse effects on the reproductive function. The serum testosterone levels were elevated significantly in the 14- and 56-nm carbon nanoparticles-exposed groups. Histological examination showed partial vacuolation of the seminiferous tubules. In addition, the effects of particle number towards the male reproductive system were investigated. The particle number controlled 14-nm nanoparticles-exposed group (14 N group, which has approximately the same particle number per unit volume as the 56-nm nanoparticles) showed fewer effects than did the 56-nm nanoparticles-exposed groups. These results suggest that carbon nanoparticle-exposure has adverse effects on the mouse male reproductive function. Furthermore, the effects of nanoparticles on the male reproductive system depend on particle mass rather than particle number.

The effects of microbial materials adhered to Asian sand dust on allergic lung inflammation.

Asian sand dust (ASD) containing microbiological materials, sulfate (SO(4)(2)), and nitrate (NO(3)(-) ) derived from air pollutants in East China, reportedly cause adverse respiratory health effects. ASD aggravates ovalbumin (OVA)-associated experimental lung eosinophilia. In this study, the toxic materials adsorbed onto ASD were excluded by heat treatment at 360 degrees C for 30 min. The effects of nonheated ASD or heated ASD (H-ASD) toward the allergic lung inflammation were compared in murine lungs. ICR mice were administered intratracheally with normal saline (control), H-ASD, ASD, OVA, OVA + H-ASD, and OVA + ASD, four times at 2-week intervals. ASD only increased neutrophils in bronchoalveolar lavage fluids (BALFs) along with pro-inflammatory mediators, such as keratinocyte chemoattractant (KC). H-ASD and ASD enhanced eosinophil recruitment induced by OVA in the alveoli and in the submucosa of the airway, which has a goblet cell proliferation in the bronchial epithelium. The two ASDs synergistically increased interleukin-5 (IL-5), monocyte chemotactic protein-3 (MCP-3), and eotaxin, which were associated with OVA, in BALF. The enhancing effects were much greater in ASD than in H-ASD. The two ASDs induced the adjuvant effects to specific IgE and IgG1 production by OVA. In the in vitro study using RAW264.7 cells, ASD increased the expression of Toll-like receptor 2 (TLR 2) mRNA but not TLR4 mRNA. H-ASD caused no expression of either TLR mRNA. These results suggest that the aggravated lung eosinophilia by ASD may be due to activation of Th2-associated immune response via the activation of TLR2 by microbial components adhered to ASD.

Developmental changes in P300 wave elicited during two different experimental conditions.

Age-related correlations on auditory event-related potentials were studied using a task-relevant oddball paradigm in 175 normal subjects aged 4-21 years and age-related correlations in the "ignore" condition were studied in 108 normal subjects aged 1-21 years. In the ignore condition, subjects more than 4 years of age were instructed to read a book to divert attention from the auditory stimulus. From 4 to about 17 years of age, the latencies of task-relevant P300 in event-related potentials (ERPs) gradually shortened. In the ignore condition experiment, the P300 latency shortened progressively, but stabilized at about 12 years of age. Whereas P300 in the ignore condition likely corresponds to P3a described previously (passive attention), the conventional P300 wave corresponds to P3b (active attention). The findings indicate a developmental difference between the P3a and P3b potential.

[Acute toxicity of intrarectally administered (ketoprofen (T10) in rat weanlings].

Acute toxicity of Ketoprofen, a nonsteroidal antiinflammatory analgestic, was studied using rat weanlings. Ketoprofen was intrarectally administered in the form of a mixture with T10, a basic materials for suppositaries. The results obtained were as follows: LD50 of KP was estimated to be 434 mg/kg in male weanlings and 496 mg/kg in female weanlings. These values were about four times higher than those obtained from our previous study (Shimpo et al., 1981) using six-weeks old adult rats of both sexes. The fact indicated that rat weanlings were far tolerant to KP intrarectally administered than young adult rats. Intrarectal administration of KP at high doses, caused death between the second and the seventh day after administration. Gross and histopathological examinations revealed that dead weanlings carried perforative peritonitis with ulcers mainly in jejunum and ileum not in rectum. It was therefore suggested that the ulcer was produced in small intestine by entero-hepatic circulation of KP and finally mortal peritonitis occurred.

[Acute toxicity of ketoprofen intrarectally administered in rats, with special reference to histopathological changes (author's transl)].

Acute toxicity was studied on Ketoprofen, one of the non-steroidal antiinflammatory analgesics, using SPF rats. Ketoprofen was intrarectally administered in three forms such as pure powder (KP), KP suspension in CMC solution (KP-CMC) and a mixture of KP with powdered basic materials of capsule (KP-T10). The results obtained were as follows:1. LD50 values of terms of KP were 84 mg/kg in male rats and 122 mg/kg in female rats when KP-CMC was administered intrarectally, and 117 mg/kg in male and 92 mg/kg in female when KP-T10 was administered intrarectally., while peroral administration of KP-CMC showed LD50 values of 68 mg/kg in males and 78 mg/kg in females in terms of KP. 2. Major toxic signs of KP were ulceration on small intestines and peritonitis. Degeneration of hepathocytes and decrease in thymus lymphocytes were also observed. 3. Minimum lethal dose of KP-T10 was slightly higher than that of KP-CMC.

[Toxicological study on the anorectal irritation and systemic organ toxicity evoked by long-term intrarectal administration of ketoprofen in rabbits (author's transl)].

Ketoprofen (KP) was administered intrarectally and perorally to rabbits weighing approximately 3 kg of both sexes for a period of 13 weeks, in order to study the anorectal irritation and chronic systemic organ toxicity of KP which was capsulated with the soft T10 capsule for rectal administration and with a hard capsule for peroral administration. Doses of capsulated drugs for one animal were 9.0 mg and 4.5 mg in terms of KP. All animals treated by these dose levels survived without showing any abnormal symptoms. Intrarectal administration of KP-T10 did not produce any mucosal lesions in digestive tracts, while peroral administration of KP with hard capsule induced ulcers in cecum or anus, and congestion in small intestines in a small number of cases. No pathological change was recognized in organs except for digestive tracts in all cases by autopsy. From the above results, it can be seen that the suppository of KP capsulated by the soft T10 does not show any irritating effect on anorectal mucosa and has no toxic effect on all organs systemically. Then, a suppository of KP-T10 can be used more harmlessly than the peroral capsulated KP.

[G-CSF and G-CSF receptor].

Relationship between leucocytosis and G-CSF blood concentration were examined. Increase in blood concentration of G-CSF of surgical patient and dialysis patient with leucocytosis were noticed. Determination of G-CSF receptor on leucocyte was performed by the flow cytometry using biotinylated G-CSF. Modulation of G-CSF receptor on leucocyte at surgery and dialysis was identified in vivo. Studies of G-CSF blood concentration and modulation of G-CSF receptor are useful in analysis of dynamics of leucocyte and analysis of infectious disease.

[Immunoglobulin class and light chain type of oligoclonal bands in CSF in children with CNS infectious diseases].

Agarose gel electrophoresis and immunofixation of CSF and serum from 16 patients aged from 1 day to 13 years with CNS infectious diseases (5 with purulent meningitis, 5 with aseptic meningitis, 4 with acute encephalitis, 1 with subdural empyema and 1 with SSPE) revealed oligoclonal IgG bands in 10 cases. In 4 cases, a high CSF/serum albumin ratio was recognized without an increase of IgG-index, probably representing a systemic immune response. Neither IgA nor IgM bands were recognized. IgG light chain was examined in 7 cases and IgG kappa bands predominated in 6 cases. IgG lambda bands predominance presented in only one case. Free IgG kappa or lambda chain was not found. These results suggested that the measurement of not only IgG-index but oligoclonal bands may have a diagnostic usefulness to know about local production of immunoglobulins in CSF.

[Effectiveness of haloperidol in the treatment of chorea minor].

Chorea minor is the most curious manifestation of rheumatic fever, first described by Sydenham in 1686. Subsequent evidence showed that chorea could be a late manifestation of rheumatic fever, often occurring several months after a streptococcal infection in contrast to other major manifestations. During the ten-year period between 1984 and 1993, 11 children with rheumatic fever were seen at our hospital, two cases of these being accompanied with chorea minor. Case 1, a male aged 12, presented with involuntary movements. He was diagnosed as having rheumatic fever because of chorea and systolic ejection murmur at the apex of the heart. Plain cranial CT was normal. However, positron emission computed tomography revealed an increased 11C-glucose uptake in the caudate nucleus as compared with the cerebral cortex. Case 2, a female aged 14, presented with involuntary movements. Plain cranial CT was normal, but single photon emission CT showed a difference between the right and left brain. These two patients were given penicillin G (PCG), predonisolone (PSL) and haloperidol. Haloperidol was administered, because PCG and PSL had no effect to improve the clinical manifestations. After administer decreased to a half with a clinical improvement, but the level of GABA did not change. Haloperidol seemed to be an effective and useful agent for motor manifestations of the disease.

[Clinical epidemiology of bronchial asthma in children report. No. III. Comparison of prevalence of asthma with 1982 and 1990 and environmental factors].

UNLABELLED: In 1982, our group carried out a survey by the questionnaires and on the site medical check-ups to observe and occurrence of asthma and other allergic symptoms in elementary and junior high school children in Izu Ohshima island. Same procedure was repeated in 1990 for 1145 children of the same age group to see any data fluctuation. The occurrence of allergic symptoms with relation to living conditions was also researched. RESULT: 114 students (11.0%) had either suffered from asthma in the past, or were still currently exhibiting symptoms, this marked a 7.5% rise (108 students) over the 1982 research data. However, patients in need of current treatment numbered 48 (4.5%), which was similar to the 1982 data of 82 (4.3%). For other allergic symptoms, rhinitis showed a marked increase over the 1982 data. The relation between living conditions and asthma was analyzed by Multiple Factor Analysis Quantification Theory. RESULT: 1) Family history of allergy, 2) Selection of food products upon starting solids during infancy, 3) Infection of lower bronchus during infancy all seemed to have had much influence on the occurrence of asthma.

Effect of glycogen synthase kinase 3 ß-mediated presenilin 1 phosphorylation on amyloid ß production is negatively regulated by insulin receptor cleavage.

Presenilin 1 (PS1), a causative molecule of familial Alzheimer's disease (AD), is known to be an unprimed substrate of glycogen synthase kinase 3 ß (GSK3ß) [Twomey and McCarthy (2006) FEBS Lett 580:4015-4020] and is phosphorylated at serine 353, 357 residues in its cytoplasmic loop region [Kirschenbaum et al. (2001) J Biol Chem 276:7366-7375]. In this report, we investigated the effect of PS1 phosphorylation on AD pathophysiology and obtained two important results--PS1 phosphorylation increased amyloid ß (Aß) 42/40 ratio, and PS1 phosphorylation was enhanced in the human AD brains. Interestingly, we demonstrated that PS1 phosphorylation promoted insulin receptor (IR) cleavage and the IR intracellular domain (IR ICD) generated by γ-secretase led to a marked transactivation of Akt (PKB), which down-regulated GSK3ß activity. Thus, the cleavage of IR by γ-secretase can inhibit PS1 phosphorylation in the long run. Taken together, our findings indicate that PS1 phosphorylation at serine 353, 357 residues can play a pivotal role in the pathology of AD and that the dysregulation of this mechanism may be causally associated with its pathology.

Naphthoquinone enhances antigen-related airway inflammation in mice.

The current authors have previously demonstrated that diesel exhaust particles (DEP) enhance antigen-related airway inflammation in mice. Furthermore, a recent study has shown that organic chemicals in DEP, rather than their carbonaceous nuclei, are important contributors to the aggravating effects of airway inflammation. However, the components in DEP responsible for the enhancing effects on the model remain to be identified. The current authors investigated the effects of naphthoquinone (NQ), one of the extractable chemical compounds of DEP, on antigen-related airway inflammation, local expression of cytokine proteins, and antigen-specific immunoglobulin (Ig) production in mice. Pulmonary exposure to NQ dose-dependently aggravated antigen-related airway inflammation, as characterised by infiltration of eosinophils and lymphocytes around the airways and an increase in goblet cells in the bronchial epithelium. Combined exposure to NQ and antigen enhanced the local expression of interleukin (IL)-4, IL-5, eotaxin, macrophage chemoattractant protein-1 and keratinocyte chemoattractant, compared with exposure to antigen or NQ alone. Also, NQ exhibited adjuvant activity for the antigen-specific production of IgG(1) and IgG(2a). These results provide the first experimental evidence that naphthoquinone can enhance antigen-related airway inflammation in vivo, and that naphthoquinone can, to some extent, partly play a role in the pathogenesis of diesel exhaust particle toxicity on the condition.

Effects of phenanthraquinone on allergic airway inflammation in mice.

BACKGROUND: Diesel exhaust particles (DEP) enhance allergic airway inflammation in mice (Takano et al., Am J Respir Crit Care Med 1997; 156: 36-42). DEP consist of carbonaceous nuclei and a vast number of organic chemical compounds. However, it remains to be identified which component(s) from DEP are responsible for the enhancing effects. 9,10-Phenanthraquinone (PQ) is a quinone compound involved in DEP. OBJECTIVE: To investigate the effects of PQ inoculated intratracheally on allergic airway inflammation related to ovalbumin (OVA) challenge. MATERIALS AND METHODS: We evaluated effects of PQ on airway inflammation, local expression of cytokine proteins, and allergen-specific immunoglobulin production in mice in the presence or absence of OVA. Results In the presence of OVA, PQ (2.1 ng/animal) significantly increased the numbers of eosinophils and mononuclear cells in bronchoalveolar lavage fluid as compared with OVA alone. In contrast, the numbers of these cells around the airways were not significantly different between OVA challenge and OVA plus PQ challenge in lung histology. PQ exhibited adjuvant activity for the allergen-specific production of IgG1 and IgE. OVA challenge induced significant increases in the lung expression of IL-4, IL-5, eotaxin, macrophage chemoattractant protein-1, and keratinocyte chemoattractant as compared with vehicle challenge. However, the combination of PQ with OVA did not alter the expression levels of these proteins as compared with OVA alone. CONCLUSION: These results indicate that PQ can enhance the immunoglobulin production and the infiltration of inflammatory cells into alveolar spaces that are related to OVA, whereas PQ seems to be partially responsible for the DEP toxicity on the allergic airway inflammation.

Precocious puberty caused by an hCG-producing tumor of the septum pellucidum.

A 6 year 9 month old boy with rapidly progressing precocious puberty was immunohistochemically and histologically diagnosed as having an hCG-producing mixed tumor consisting of choriocarcinoma and teratoma in the septum pellucidum. His serum hCG was elevated, but the serum LH was low as determined by LH immunoradiometric assay (IRMA). He did not exhibit a characteristic endocrinological pattern, e.g., high basal levels of LH and failure to respond with high LH levels to the LH-RH stimulation test using the conventional LH RIA method.

[Measurement of the abrasion of radioactive teeth by dentifrices].

The purpose of this study is to assess the dentifrice abrasivity of both commercially available products and test products. The assessment of abrasivity was carried out by the measurement of 32P released from tooth by using radioactive dentifrice abrasion (RDA) method. In dentine, RDA values, which show the polishing ability for dentine, were 65-100 with dentifrices with normal cleaning power and 106-182 with those with high cleaning power, respectively. On the other hand, REA values which show the polishing ability for enamel were 12-405 with both market products and test products. The difference of the REA values according to the dentifrices appears to be largely influenced by the difference of polishing agents of each dentifrice. It is concluded that RDA method is usefull for assessing of dentifrice abrasivity. However, particular attention should be given to the abrasion of dentine.