Regulation of ER molecular chaperone prevents bone loss in a murine model for osteoporosis

Endoplasmic reticulum (ER) stress response is important for protein maturation in the ER. Some murine models for bone diseases have provided significant insight into the possibility that pathogenesis of osteoporosis is related to ER stress response of osteoblasts. We examined a possible correlation between osteoporosis and ER stress response. Bone specimens from 8 osteoporosis patients and 8 disease-controls were used for immunohistochemical analysis. We found that ER molecular chaperones, such as BiP (immunoglobulin heavy-chain binding protein) and PDI (protein-disulfide isomerase) are down-regulated in osteoblasts from osteoporosis patients. Based on this result, we hypothesized that up-regulation of ER molecular chaperones in osteoblasts could restore decreased bone formation in osteoporosis. Therefore, we investigated whether treatment of murine model for osteoporosis with BIX (BiP inducer X), selective inducer BiP, could prevent bone loss. We found that oral administration of BIX effectively improves decline in bone formation through the activation of folding and secretion of bone matrix proteins. Considering these results together, BIX may be a potential therapeutic agent for the prevention of bone loss in osteoporosis patients.     

JPN Guidelines for the management of acute pancreatitis: severity assessment of acute pancreatitis

This article addresses the criteria for severity assessment and the severity scoring system of the Ministry of Health and Welfare of Japan; now the Japanese Ministry of Health, Labour, and Welfare (the JPN score). It also presents data comparing the JPN score with the Acute Physiology and Chronic Health Evaluation (APACHE) II score and the Ranson score, which are the major measuring scales used in the United States and Europe. The goal of investigating these scoring systems is the achievement of earlier diagnosis and more appropriate and successful treatment of severe or moderate acute pancreatitis, which has a high mortality rate. This article makes the following recommendations in terms of assessing the severity of acute pancreatitis: (1) Severity assessment is indispensable to the selection of proper initial treatment in the management of acute pancreatitis (Recommendation A). (2) Assessment by a severity scoring system (JPN score, APACHE II score) is important for determining treatment policy and identifying the need for transfer to a specialist unit (Recommendation A). (3) C-reactive protein (CRP) is a useful indicator for assessing severity (Recommendation A). (4) Contrast-enhanced computed tomography (CT) scanning and contrast-enhanced magnetic resonance imaging (MRI) play an important role in severity assessment (Recommendation A). (5) A JPN score of 2 or more (severe acute pancreatitis) has been established as the criterion for hospital transfer (Recommendation A). (6) It is preferable to transfer patients with severe acute pancreatitis to a specialist medical institution where they can receive continuous monitoring and systemic management.     

Masticatory performance in older subjects with varying degrees of tooth loss

Objectives

The purpose of this study was to establish the factors influencing the masticatory performance of older subjects with varying degrees of tooth loss and associated numbers of posterior occlusal contacts.

Methods

The subjects consisted of 1274 independently living people aged 60 years and over. Individuals with partially or fully edentulous arches without a denture replacement or those having any symptoms related to an oral problem were excluded from the study participants. Masticatory performance, maximal occlusal force and stimulated whole saliva were measured. Subjects were grouped into three categories by posterior occlusal contact, according to the Eichner Index. Group A had contacts in four support zones; group B had one to three zones of contact or contact in the anterior region only; and group C had no support zones at all, although a few teeth could still remain.

Results

The masticatory performance in groups B and C was found to be 81% and 50% of that of group A, respectively. The multiple linear regression analysis showed that in all the groups, occlusal force was significantly associated with masticatory performance. In groups A and B, the number of residual teeth was significantly associated with masticatory performance, whereas in group C, it had no significant relationship with masticatory performance. Salivary flow rate had a significant correlation with masticatory performance only in group C.

Conclusions

Declines in occlusal contact, occlusal force and salivary flow appear to be associated with reduction of masticatory performance in older adults. However, the crucial factors for masticatory performance varied, depending on the phase of occlusal collapse.     

Influence of early cerebrospinal fluid-guided diagnosis and early high-dose corticosteroid therapy on ocular outcomes of Vogt–Koyanagi–Harada disease

PURPOSE: To evaluate the importance of early cerebrospinal fluid (CSF)-guided diagnosis and early high-dose corticosteroid therapy on the complications and visual prognosis of Vogt-Koyanagi-Harada (VKH) disease. PATIENTS AND METHODS: Charts from patients with VKH disease who had been seen at Tokyo Medical and Dental University Hospital and Miyata Eye Hospital between 1994 and 2002 were retrospectively reviewed. The patients were classified into two groups. The first group (group A) consisted of patients who had received a full work-up including CSF examination and corticosteroid pulse therapy at the acute ophthalmic stage of disease. The second group (group B) consisted of patients who were referred to us by local ophthalmologists long after the disease onset, had not had a CSF examination and had been treated with low-dose systemic corticosteroids or topical corticosteroid therapy. The ocular complications, systemic complications and visual prognosis were compared between the two groups. RESULTS: Twenty-two patients were included in group A and ten patients in group B. The initial diagnosis at the acute ophthalmic stage had been VKH disease in all patients of group A, while, in group B, the diagnosis was idiopathic uveitis in six patients (60%) initially. Frequency of recurrent uveitis and integumentary symptoms were significantly lower in group A. Intensity of sunset glow fundus was significantly more severe in group B. All eyes in group A obtained a final visual acuity of 0.8 or better, whereas 11 eyes (55%) in group B were below this level. CONCLUSIONS: The results indicate that early diagnosis, helped by CSF examination and early high-dose corticosteroid therapy, decreased the complication rate and improved the visual prognosis.     

Superselective intraarterial chemotherapy using low dose CBDCA and Pirarubicin with concurrent radiotherapy for head and neck cancer

To study the effects of superselective intraarterial chemotherapy with low-dose CBDCA, Pirarubicin, and concurrent radiotherapy on head and neck cancer, we compared primary cancer response and histopathological effective grades in 66 patients (more than T2) divided into radical and preoperative radiotherapy groups. The radical group (n=33) showed a 75.7% response in primary cancer, i.e. 54.5% complete remission and 21.2% partial remission. The preoperative group (n = 33) showed 39.4% complete remission when the histopathological effective grade was higher, and 57.6% partial remission when the grade was lower. Cancer response was better in the oral cavity, mesopharynx, and hypopharynx than in the parasinus. In the preoperative group, 5-year overall survival was 84.4% when the effective grade was higher, and 29.4% when the grade was lower. Survival differed significantly (P<0.01) between higher and lower grades. Additional postoperative therapy is thus essential in patients with lower grades of histopathological effectiveness.     

Three adult cases with Corynebacterium propinquum respiratory infections in a community hospital

Corynebacterium propinquum, which is included in Corynebacterium group ANF-3, exists as a commensal in the oral flora. This organism has not yet been fully recognized as a respiratory pathogen. We previously reported that the first case with respiratory infection caused by C. propinquum. On the other hand, Corynebacterium pseudodiphtheriticum is recognized as a causative organism in respiratory infections. Recently we experienced two cases with C. propinquum respiratory infections in our hospital. Three types of the onset such as a community-acquired infection, a hospital-acquired infection, and a nursing home acquired infections were observed. Our analysis indicated that gram staining of the purulent sputum is an essential tool to evaluate whether C. propinquum is a respiratory pathogen or not, because this organism is a commensal bacteria.     

Mondini dysplasia with recurrent bacterial meningitis caused by three different pathogens

Mondini dysplasia is rare, but has an important association with recurrent bacterial meningitis. We herein describe the case of a 3‐year‐old girl with unilateral sensorineural hearing loss who presented with three independent episodes of bacterial meningitis within 8 months. Temporal bone computed tomography indicated the characteristic features of Mondini dysplasia in the right inner ear. This was treated by surgical closure of the inner ear defect via oval window and additional vaccination was administered. Appropriate vaccination might prevent the recurrent bacterial meningitis associated with Mondini dysplasia.     

Rebamipide Attenuates Indomethacin-Induced Gastric Mucosal Lesion Formation by Inhibiting Activation of Leukocytes in Rats

Granulocyte elastase released from activatedleukocytes plays an important role in leukocyteinfiltration. Since activated leukocytes have been shownto be involved in the pathogenesis of gastric mucosal lesion formation induced by nonsteroidalantiinflammatory drugs, inhibition of granulocyteelastase release from activated leukocytes may be usefulin the prevention of these lesions. Rebamipide, a novel antiulcer agent, inhibited granulocyte elastaserelease from activated neutrophils in vitro. Rebamipideand ONO-5046, a granulocyte elastase inhibitor, markedlyinhibited gastric mucosal lesion formation in rats. Gastric myeloperoxidase activity wassignificantly increased 3 hr after indomethacinadministration. This increase was significantlyinhibited by rebamipide and ONO-5046. Cimetidine did notinhibit granulocyte elastase release from activatedneutrophils. Although cimetidine markedly prevented theindomethacin-induced gastric mucosal lesion formation,it did not reduce the gastric myeloperoxidase activity. Therefore, unlike cimetidine, rebamipide mayprevent indomethacin-induced gastric mucosal lesionformation by inhibiting neutrophil activation.