Understanding the Mechanism of Bacterial Persistent Infection-Using Bartonella henselae Infection as a Model

巴東體屬感染症為國際認知的重要新興傳染病，其中包括廣為人知B.henselae 引起的貓抓熱。由於過去貓感染B. henselae 所造成的持續性菌血症(可長達一年以上)並無法使用抗生素進行有效清除，引起疾病防治上的困難。又目前國外正進行此菌的疫苗研發。皆需深入瞭解此菌造成持續性感染的可能機轉。於過去半年中，本研究室已完成B. henselae 於台灣地區貓族群之初步流行病學調查，並完成B. henselae 於愛滋病患者之分子流行病學研究。研究結果顯示依16S rDNA 分型結果之兩分子型B. henselae 可能與其不同致病力有關，值得進一步探討其機轉。本計劃將利用所分離人與貓之B. henselae 基因亞型 I 與基因亞型II 菌株進行活體外感染巨噬細胞的研究，比較此二亞型對巨噬細胞侵入作用與刺激細胞激素產生作用的差異，進行細菌性疾病持續性感染的模式建立與機轉初步探討

Improved peripheral nerve regeneration in streptozotocin-induced diabetic rats by oral lumbrokinase

[[abstract]]We assessed the therapeutic effects of lumbrokinase, a group of enzymes extracted from the earthworm, on peripheral-nerve regeneration using well-defined sciatic nerve lesion paradigms in diabetic rats induced by the injection of streptozotocin (STZ). We found that lumbrokinase therapy could improve the rats' circulatory blood flow and promote the regeneration of axons in a silicone rubber conduit after nerve transection. Lumbrokinase treatment could also improve the neuromuscular functions with better nerve conductive performances. Immunohistochemical staining showed that lumbrokinase could dramatically promote calcitonin gene-related peptide (CGRP) expression in the lamina I-II regions in the dorsal horn ipsilateral to the injury and cause a marked increase in the number of macrophages recruited within the distal nerve stumps. In addition, the lumbrokinase could stimulate the secretion of interleukin-1 (IL-1), nerve growth factor (NGF), platelet-derived growth factor (PDGF), and transforming growth factor-β (TGF-β) in dissected diabetic sciatic nerve segments. In conclusion, the administration of lumbrokinase after nerve repair surgery in diabetic rats was found to have remarkable effects on promoting peripheral nerve regeneration and functional recovery

Effects of Taxol on Regeneration in a Rat Sciatic Nerve Transection Model

[[abstract]]Recent studies describe taxol as a candidate treatment for promoting central nerve regeneration. However, taxol has serious side effects including peripheral neurotoxicity, and little information is known about the effect of taxol on peripheral nerve regeneration. We investigated the effects of taxol on regeneration in a rat sciatic nerve transection model. Rats were divided into four groups (n = 10): normal saline (i.p.) as the control, Cremophor EL vehicle, and 2 or 6 mg/kg of taxol in the Cremophor EL solution (four times in day-2, 4, 6, and 8), respectively. We evaluated neuronal electrophysiology, animal behaviour, neuronal connectivity, macrophage infiltration, location and expression levels of calcitonin gene-related peptide (CGRP), and expression levels of both nerve growth factors and immunoregulatory factors. In the high-dose taxol group (6 mg/kg), neuronal electrophysiological function was significantly impaired. Licking latencies were significantly changed while motor coordination was unaffected. Neuronal connectivity, macrophage density, and expression levels of CGRP was dramatically reduced. Expression levels of nerve growth factors and immunoregulatory factors was also reduced, while it was increased in the low-dose taxol group (2 mg/kg). These results indicate that taxol can modulate local inflammatory conditions, impair nerve regeneration, and impede recovery of a severe peripheral nerve injury