Behavioral analysis of zopiclone on the basis of their discriminative stimulus properties in the rat

Zopiclone is a new cyclopyrrolone derivative which exerts pharmacological activities similar to those of benzodiazepines in behavioral and biochemical studies. In order to clarify the discriminative stimulus properties of zopiclone, 8 rats were trained to discriminate the interoceptive stimulus induced by zopiclone (3.2 mg/kg, i.p.) from those of saline. Following discrimination acquisition, administration of zopiclone resulted in drug-appropriate responding with an ED50 of 1.3 (1.0-1.8) mg/kg. The zopiclone discriminative stimulus generalized to the benzodiazepines diazepam (1.8 mg/kg), nitrazepam (10 mg/kg) and alprazolam (10 mg/kg). A non-benzodiazepine, suriclone, at 3.2 mg/kg, generalized to the zopiclone stimulus in 5 out of 7 rats, but meprobamate, hydroxyzine, tracazolate and muscimol did not. The benzodiazepine antagonist Ro 15-1788 (1 mg/kg) completely blocked zopiclone stimulus. In contrast, however, bicuculline and pentetrazol failed to antagonize it. The serotonin antagonist cinanserin and ritanserin neither generalized to the zopiclone stimulus nor did they exhibit antagonism. These results suggest that the zopiclone discriminative stimulus is mediated by binding to benzodiazepine receptors and appears not to be related to GABAergic or serotonergic system.     

Role of CD 11/CD 18 in neutrophil emigration during acute and recurrent Pseudomonas aeruginosa-induced pneumonia in rabbits.

This study examined CD11/CD18-mediated adhesion in neutrophil emigration during acute and recurrent Pseudomonas aeruginosa-induced pneumonia. Neutrophil emigration during acute pneumonia was studied in anti-CD18 antibody or murine-IgG-pretreated rabbits 4 hours after intrabronchial instillation of P. aeruginosa. To examine emigration in recurrent pneumonias, rabbits given P. aeruginosa on day 0 received anti-CD18 antibody or IgG on day 7. A second instillate was placed either at the initial site or in a separate lobe, and emigration into alveolar spaces was quantitated morphometrically after 4 hours. The results show that CD11/CD18 was required for neutrophil emigration in acute pneumonias and in recurrent pneumonias that occurred at a site distant from the initial infection. However, when the recurrent pneumonia occurred in the previously inflamed site, CD11/CD18 was not required. When the same number of organisms were instilled on days 0 and 7, emigration was reduced to 15 to 20 percent of the number that migrated initially and only CD18-independent adhesion pathways were used. Increasing the concentration of organisms threefold increased emigration through both CD18-dependent and CD18-independent pathways. These data indicate that P. aeruginosa induces CD11/CD18-dependent emigration during acute pneumonia and recurrent pneumonia at previously uninflamed sites. However, adhesion pathways are altered in regions of chronic inflammation, and a greater proportion of neutrophil emigration occurs through CD11/CD18-independent pathways.     

Post-ischemic Intravenous Administration of Allogeneic Dental Pulp-Derived Neurosphere Cells Ameliorated Outcomes of Severe Forebrain Ischemia in Rats

Background

Transplantation of bone marrow or adipose-derived mesenchymal stem cells (MSCs) for various neurological disorders has yielded promising results in models of focal cerebral ischemia. Dental pulp stem cells (DPSCs) are a type of MSC. In serum-free culture, they can form neurospheres that contain nestin-positive neuronal progenitor cells. We hypothesized that transplantation of dental pulp-derived neurosphere cells would ameliorate outcomes of global cerebral ischemia, the pathophysiology of which is known to resist conventional treatments.We also hypothesized that transplantation of dental pulp-derived cells would provide some neuroprotection in this pathology due to the presence of DPSCs.

Methods

Using adult rats, ischemia was induced by two-vessel occlusion of both carotid arteries in combination with systemic hypotension. Allogeneic dental pulp cells from juvenile rats were cultured in advance in serum-free medium to obtain neurospheres. Dental pulp-derived neurosphere cells or dental pulp-derived cells were intravenously administered at 3 h after ischemic insult, with normal saline as a control. Animals were observed for 14 days after ischemia. Neurological outcome was assessed using the water-maze test and neuromotor test. Histological outcome was measured by counting the percentage of dead neurons in the hippocampal CA1 and CA3 regions.

Results

Transplantation of both dental pulp-derived neurosphere cells and dental pulp-derived cells significantly improved survival rate and water-maze test results. Neurosphere cell transplantation was related to significantly better neuromotor test and histological outcomes, as indicated by the reduced percentage of dead neurons in CA1.

Conclusions

Transplantation of dental pulp-derived neurosphere cells ameliorated outcomes of global cerebral ischemia. It was also demonstrated that dental pulp-derived cell administration provided some neuroprotection.

     

Analysis of the Pattern of Maxillofacial Fracture by Five Departments in Tokyo: A Review of 674 Cases

We studied maxillofacial fractures treated by departments of oral and maxillofacial surgery in Tokyo. A retrospective review of records and radiographs for patients admitted during the 5-year period from 2000 to 2004 was conducted at five departments in Tokyo. Date, age, gender, cause of injury, fracture site, concomitant injury, domestic violence against women, and treatment were reviewed. 674 patients with maxillofacial fractures were admitted. Male-to-female ratio was 3.6 : 1. The most frequent age group was 21–25 years. Fractures of the mandible were most frequent (87%), followed by the maxilla (14%) and the zygomatic bone (12%). Thirty-one percent of fractures were due to traffic accidents, 29% to accidental falls, 23% to violence and 14% to sports. The incidence of maxillofacial fractures caused by traffic accidents was lower, and that caused by falls and violence were higher than in other countries. Seventeen percent of the maxillofacial fracture patients had concomitant injuries. The incidence of domestic violence-related maxillofacial fracture was 1.6% of all cases. These cases were mainly caused by a husband (55%) or a sexual partner (36%). Most patients (67%) were treated by open reduction surgery. However, condylar fracture alone was usually treated by closed reduction surgery.     

Rare pneumoconiosis induced by long-term amorphous silica exposure: the histological characteristics and expression of cyclooxygenase-2 as an antifibrogenic mediator in macrophages

Pneumoconiosis induced by non-crystalline silica is considered rare, although silicosis resulting from contact with crystalline silica is a well-known hazard associated with progressive pulmonary fibrosis. Here we describe a patient with pneumoconiosis induced by diatomaceous earth composed of amorphous silica detected by two-dimensional imaging of chemical elements. The histology revealed that the disease was characterized by a granulomatous reaction in the lung. A large number of macrophages laden with yellow and black pigments accumulated in alveolar spaces and were incorporated into the interstitial sites. Bronchiolar walls were destroyed by palisade macrophages, suggesting airflow obstruction. Packed macrophages adhering to and covering the denuded interstitium indicated that macrophages might be incorporated into pulmonary interstitium in this fashion. Immunohistochemistry showed that cyclooxygenase-2, an antifibrogenic mediator, was intensely expressed in the macrophages compared with macrophages in control lungs. No birefringent material was found in the tissues. When two-dimensional analysis of chemical elements was performed using an electron probe microanalyzer with a wavelength-dispersive spectrometer, the resultant fine mapping of silicon and oxygen on the tissue indicated that the pigments phagocytosed by macrophages corresponded to amorphous silica. In conclusion, two-dimensional analysis of elements is very useful for pathologists in correlating the presence of chemical elements with histological changes.     

The effcct of eel bone powder on bone mineral density in mouse femoral bone

Improvement in bone mineral density (BMD) in the femur after administration of eel bone powder (EBP) was evaluated in ovariectomized (OVX) mice. Female ICR mice were given ovariectomies or sham operations at 9 weeks of age, then housed for 2 weeks during which they were allowed free access to a normal diet. Subsequently, the mice were divided into 3 groups: sham-operated mice fed a normal diet, OVX mice fed a normal diet, and OVX mice fed a diet containing EBP. After the mice in these 3 groups had been housed for 2 months (during which time they were allowed free access to their respective diets), they were dissected and analyzed. The BMD values in the removed femurs were measured by peripheral quantitative computed tomography (pQCT). Femoral total and femoral cancellous BMD values were higher in the EBP-treated group than in the nontreated group. Total BMD: the value in the EBP-treated group was 573 mg/cm³, and that in the non-treated group was 451 mg/cm³ (p<0.05). Cancellous BMD: the value in the EBP-treated group was 242 mg/cm³, and that in the non-treated group was 143 mg/cm³ (p<0.05). However, cortical BMD values did not significantly differ between the EBP-treated group and the non-treated group. Cortical BMD: The value in the EBP-treated group was 1891 mg/cm³, and that in the non-treated group was 1900 mg/cm³. pQCT was used to measure the cortical and cancellous BMD in the long bones. By use of a color conversion technique to display BMD, regional changes in the long bones can be expressed and easily measured. It has been well documented that EBP is effective for improvement or prevention of BMD reduction associated with OVX.     

Non‐equilibrium atmospheric pressure plasmas modulate cell cycle‐related gene expressions in melanocytic tumors of RET‐transgenic mice

The incidence of cutaneous malignant melanoma is increasing at a greater rate than that of any other cancer in the world. However, an effective therapy for malignant melanoma has not been established. Recently, some studies have shown an antitumor effect of non‐equilibrium atmospheric pressure plasmas (NEAPPs) in vitro. Here, we examined the in vivo effect of NEAPP on cell cycle regulators, key elements for malignant transformation, in spontaneously developed benign melanocytic tumors in a hairless animal model. NEAPP irradiation decreased expression levels of cell cycle promoters, Cyclin D1, E1 and E2, and increased expression level of a cell cycle repressor, p27^KIP1. Cyclin D1, E1 and E2 and p27^KIP expression levels were associated with malignant transformation of the benign tumor in the animal model. Our results suggest that NEAPP irradiation suppresses malignant transformation of a benign melanocytic tumor via control of the expression levels of cell cycle regulators.