Application of the Luminescence Syncytium Induction Assay to Identify Chemical Compounds That Inhibit Bovine Leukemia Virus Replication.

Bovine leukemia virus (BLV) infection causes endemic bovine leukemia and lymphoma, resulting in lower carcass weight and reduced milk production by the infected cattle, leading to economic losses. Without effective measures for treatment and prevention, high rates of BLV infection can cause problems worldwide. BLV research is limited by the lack of a model system to assay infection. To overcome this, we previously developed the luminescence syncytium induction assay (LuSIA), a highly sensitive and objectively quantifiable method for visualizing BLV infectivity. In this study, we applied LuSIA for the high-throughput screening of drugs that could inhibit BLV infection. We screened 625 compounds from a chemical library using LuSIA and identified two that markedly inhibited BLV replication. We then tested the chemical derivatives of those two compounds and identified BSI-625 and -679 as potent inhibitors of BLV replication with low cytotoxicity. Interestingly, BSI-625 and -679 appeared to inhibit different steps of the BLV lifecycle. Thus, LuSIA was applied to successfully identify inhibitors of BLV replication and may be useful for the development of anti-BLV drugs.

Refractory liver dysfunction was remarkably improved with chelating agents of Wilson's disease, in a patient with systemic lupus erythematosus-like syndrome after a parvovirus B19 infection.

Parvovirus B19 infection has been reported to be associated with systemic lupus erythematosus (SLE). Liver dysfunction is frequently observed in SLE patients. However, liver dysfunction caused by an aberrant copper metabolism is rarely seen in patients with parvovirus B19 infection. We report a rare case of SLE-like and Wilson's disease (WD) mimicking symptoms that were simultaneously triggered by parvovirus B19 infection. A 29-year-old man was admitted to our hospital with high-grade fever, arthralgia, and oral ulcers following a parvovirus B19 infection. Laboratory tests showed elevated transaminase levels, proteinuria, anti-double-stranded DNA antibody, high levels of serum ferritin, and leukocytopenia. He was suspected of having SLE with haemophagocytosis and was treated with high doses of prednisolone. Subsequently, the patient's arthritis symptoms improved and the proteinuria improved. Immunosuppressive therapies improved most of his symptoms except for the high titre of transaminases were alleviated. Laboratory findings indicated low serum levels of ceruloplasmin and copper along with elevated levels of 24-hour urinary copper. Liver biopsy detected copper in hepatocytes. Although the hepatic copper content was relatively low in this case, the dysregulation of copper metabolism was considered to be a main cause of his elevated levels of liver enzymes. Therefore, we started treatment with chelating agents used in WD treatment. At the 2-month follow-up, the liver dysfunction had significantly improved. Our case suggests that in patients with refractory liver dysfunction due to unknown reasons, it is necessary to exclude the possibility that an abnormal copper metabolism had caused an increase in the levels of liver enzymes.

Differential effect of concomitant antidiabetic agents on carotid atherosclerosis: a subgroup analysis of the PROLOGUE study.

Accumulated evidence shows that some antidiabetic agents attenuate the progression of carotid atherosclerosis assessed as intima-media thickness (IMT). Although some studies have demonstrated an inhibitory effect of dipeptidyl peptidase-4 inhibitors on carotid IMT progression, in the PROLOGUE study sitagliptin failed to slow progression relative to conventional therapy for 24 months. We hypothesized that differences in the concomitant antidiabetic agents between the groups have influenced the progression of carotid IMT. We performed a post hoc analysis of the PROLOGUE study using subgroups stratified by concomitant antidiabetic agents. Although no subgroup with any combination of agents in the overall patients showed a significant difference between sitagliptin group and conventional therapy group in the changes from baseline in mean common carotid artery (CCA)-IMT at 24 months, a significant attenuation of mean CCA-IMT progression was observed in the sitagliptin group relative to conventional therapy group only in three combination subgroups aged < 70 years, namely no thiazolidinedione; no thiazolidinedione or biguanide; and no thiazolidinedione, biguanide or α-glucosidase inhibitor, even after adjustment for multiple confounding factors. In the three subgroups, no significant difference between sitagliptin group and conventional therapy group in the changes from baseline in HbA1c at 24 months was detected. Our data suggest that some concomitant agents, whose prescription frequencies were increased in the conventional therapy group, may have masked the inhibitory effect of sitagliptin on carotid IMT progression in the PROLOGUE study.

True aneurysm of the facial artery.

True aneurysm of the facial artery is extremely rare. We describe a case of true facial aneurysm of the submandibular lesion in a 73-years-old man. A color Doppler ultrasonography and computed tomography (CT) revealed a 2.1 cm x 1.5 cm aneurysm with turbulent arterial flow and some thrombus inside the lumen. At the operation, the aneurysm was excised and proximal and distal ends of the facial artery were ligated. The histopathologic examination confirmed a true aneurysm of the facial artery with degenerative changes of the wall and some thrombus in the lumen. The postoperative course was uneventful, and no recurrence has been noted in more than 1-year follow-up.

Role of platelet-derived growth factor in airway remodeling in rhinosinusitis.

BACKGROUND: The purpose of this study was to elucidate the role of platelet-derived growth factor (PDGF) in the pathogenesis of rhinosinusitis. METHODS: Nasal mucosa and polyps were obtained during surgery in patients with allergic rhinitis, chronic rhinosinusitis (CRS) without asthma, and CRS with asthma. PDGF concentrations in nasal discharge were measured, and the histological distribution and expression levels of mRNA for PDGF and PDGF receptors were examined. PDGF-producing cells were determined by double-staining for PDGF and CD68 or major basic protein. RESULTS: The concentration of PDGF was significantly higher in CRS with asthma. An immunohistochemical study showed that PDGF was localized in epithelial cells, gland cells, vascular endothelial cells, and inflammatory cells. Expression of PDGF increased in epithelial cells in all three diseases, in macrophages in CRS without asthma, and eosinophils in CRS with asthma, and PDGF receptors were detected in epithelial cells and submucosal fibroblasts. Increased expression of PDGF mRNA was found in CRS with asthma. CONCLUSION: The results indicate that PDGF is produced by macrophages, eosinophils, and epithelial cells in rhinosinusitis and that it acts on receptors in epithelial cells and fibroblasts. PGDF may be an important cytokine in the pathogenesis of rhinosinusitis by promoting tissue fibrosis and formation of nasal polyps.

Endoscopic ligation of the sphenopalatine artery and the maxillary artery for the treatment of intractable posterior epistaxis.

BACKGROUND: Intractable posterior epistaxis sometimes requires intensive treatment, such as surgery or embolization. Maxillary artery ligation has been widely used for the treatment of intractable posterior epistaxis. It is highly effective, but significant complications may occur, including an oroantral fistula and damage to the infraorbital nerve. Embolization is less invasive and can be performed in poor surgical candidates. However, it has more serious complications, such as facial nerve paralysis and hemiplegia. This investigation evaluates the effectiveness and complications of endoscopic ligation of the sphenopalatine or maxillary artery for the treatment of intractable posterior epistaxis. METHODS: Between April 2003 and March 2007, 46 patients were hospitalized for the treatment of severe posterior epistaxis in our University Hospital. Thirty patients were successfully treated by anterior and/or posterior nasal packing, and five patients were treated by electrocoagulation. Endoscopic ligation was performed under general anesthesia in 11 patients (6 men and 5 women; age range, 50-80 years). RESULTS: Eight patients underwent endoscopic ligation of the sphenopalatine artery, and three patients underwent endoscopic ligation of the maxillary artery through the middle meatus and posterior antral wall opening. There were no complications, and the patients' postoperative courses were uneventful. Recurrent epistaxis occurred in one patient on oral anticoagulants 15 months after ligation of the sphenopalatine artery, and it was successfully treated by anterior nasal packing. CONCLUSION: Endoscopic ligation of the sphenopalatine or maxillary artery is safer than arterial embolization and is less invasive than transantral ligation of the maxillary artery. This technique appears to be a simple and highly effective surgical treatment for patients with intractable posterior epistaxis.

[Image-guided endoscopic sinus surgery: a comparison of two navigation systems].

We evaluated the effectiveness of two navigation systems with optical tracking in endoscopic sinus surgery (ESS). The Signa SP/i Intraoperative navigation system (General Electric Co., Intraoperative NS) is advantageous in acquiring both real time and high-resolution images during surgery, compared to conventional image-guided navigation (Stealth Station TREON, Medtronic Inc., IGNS) that rely entirely on preoperative three-dimensional images. We studied the following in 14 patients treated with intraoperative NS and 19 treated with IGNS: 1) additional time for navigation system implementation, 2) available instrumentations in ESS, and 3) navigation system accuracy. Navigation systems required additional time to prepare ESS. The time lapse from admittance to the operating room to ESS onset was measured in patients under both systems and controls undergoing ESS without any image guidance. Preparation of the intraoperative NS required an additional 52 min and IGNS required 17 min compared to the control group. Based on operative instruments, the intraoperative NS has some limitations arising from the application of a high magnetic field. Surgical instruments must not be attracted by the magnetic field in the operating room. So those used in our study were thoroughly examined and some remanufactured using MR safe materials. All instruments in ESS could be used in surgical guidance during surgery in the IGNS. Anatomic landmarks were accurately visualized using intraoperative NS and IGNS. Intraoperative NS renews the image during surgery, so surgeons could confirm the surgical outcome during ESS. Since the average distant error in both systems was between 1 mm and 2.5 mm, we confirmed that accuracy obtained with both navigation system was suitable for ESS completion. The intraoperative NS renewed the image during navigation. In conclusion, both navigation systems are sufficient for accurate image navigation in ESS, but navigation systems must be selected based on the individual case.

Cavernous haemangioma of the internal auditory canal: a case report.

We report a patient with a cavernous haemangioma of the internal auditory canal (IAC). A 47-year-old man presented with a left profound hearing loss and a left facial palsy that had progressed over 5 years. With a preoperative diagnosis of acoustic or facial nerve neurinoma, the tumour was removed totally by a translabyrinthine approach. Intraoperatively, the tumour appeared red; it compressed the facial and cochlear nerves, and adhered to the vestibular nerve. The tumour was diagnosed as a cavernous haemangioma upon histologic and immunohistochemical examination. No recurrence of tumour occurred, but hearing loss and left facial palsy persisted. Although cavernous haemangiomas of the IAC is found in small size less than 10 mm, they often cause severe hearing loss and facial palsy. Our patient had no improvement of facial palsy, but many reports describe recovery of facial nerve function.