Background: Pruritus is a distressing symptom of cholestatic, inflammatory, and malignant liver diseases. It is a common symptom in many biliary and cholestatic disorders such as primary biliary cirrhosis (PBC). Sever...Background: Pruritus is a distressing symptom of cholestatic, inflammatory, and malignant liver diseases. It is a common symptom in many biliary and cholestatic disorders such as primary biliary cirrhosis (PBC). Several mechanisms are generally accepted as possible explanations to the underlying basis of itch. However, the exact pathophysiology of pruritus in liver diseases remains unclear. The cutaneous and central neurobiology of pruritus is complex and underlies a regulation of variable mechanisms. At present, not all mechanisms including neuromediators and receptors are known. Objective: Our objective is to evaluate whether the expression pattern of NGF and its receptor TrK A has a role in pruritus in a group of Egyptian cirrhotic patients. Patients and Methods: Forty Patients with liver cirrhosis were enrolled in the study depending on clinical evidence of stigmata of chronic liver disease (e.g. jaundice, ascites, palmar erythema, spider naevi, etc.) and ultrasonographic features of liver cirrhosis (e.g. coarse echo texture, shrunken liver, etc.). Patients were divided into two groups. Group (1): included 20 patients cirrhotic patients without pruritus. Group (2): included 20 patients cirrhotic patients with pruritus. A group of age and sex matched healthy twenty volunteers as a control. Results: After evaluation of histopathological using hematoxylin and eosin stained sections (H&E) was done. There was positive correlation between NGF protein expression and severity of pruritus in cirrhotic patients with pruritus (r = 0.876, p value ≤ 0.001). Also there was positive correlation between TrK A protein expression and severity of pruritus in cirrhotic patients with pruritus (r = 0.44, p value ≤ 0.05). Conclusions: We report, for the first time, role of these proteins (NGF/TrK A) in the mechanism of pruritus in cirrhotic patients and may provide a potential target for new treatment of pruritus in cirrhotic.展开更多
文摘Background: Pruritus is a distressing symptom of cholestatic, inflammatory, and malignant liver diseases. It is a common symptom in many biliary and cholestatic disorders such as primary biliary cirrhosis (PBC). Several mechanisms are generally accepted as possible explanations to the underlying basis of itch. However, the exact pathophysiology of pruritus in liver diseases remains unclear. The cutaneous and central neurobiology of pruritus is complex and underlies a regulation of variable mechanisms. At present, not all mechanisms including neuromediators and receptors are known. Objective: Our objective is to evaluate whether the expression pattern of NGF and its receptor TrK A has a role in pruritus in a group of Egyptian cirrhotic patients. Patients and Methods: Forty Patients with liver cirrhosis were enrolled in the study depending on clinical evidence of stigmata of chronic liver disease (e.g. jaundice, ascites, palmar erythema, spider naevi, etc.) and ultrasonographic features of liver cirrhosis (e.g. coarse echo texture, shrunken liver, etc.). Patients were divided into two groups. Group (1): included 20 patients cirrhotic patients without pruritus. Group (2): included 20 patients cirrhotic patients with pruritus. A group of age and sex matched healthy twenty volunteers as a control. Results: After evaluation of histopathological using hematoxylin and eosin stained sections (H&E) was done. There was positive correlation between NGF protein expression and severity of pruritus in cirrhotic patients with pruritus (r = 0.876, p value ≤ 0.001). Also there was positive correlation between TrK A protein expression and severity of pruritus in cirrhotic patients with pruritus (r = 0.44, p value ≤ 0.05). Conclusions: We report, for the first time, role of these proteins (NGF/TrK A) in the mechanism of pruritus in cirrhotic patients and may provide a potential target for new treatment of pruritus in cirrhotic.
文摘目的探讨神经前体细胞表达发育调控样蛋白(Nedd4L)通过泛素化降解癌蛋白神经生长因子酪氨酸激酶受体(Trk A)抑制老年前列腺癌的分子作用机制。方法收集手术切除的43例老年前列腺癌组织及对应癌旁组织标本。免疫组化染色检测Nedd4L及Trk A的表达,在人前列腺癌LNCa P细胞中转染Nedd4L特异性si RNA后,采用q RT-PCR及Western印迹检测LNCa P细胞内Trk A m RNA及蛋白的表达变化。结果Nedd4L蛋白在老年前列腺癌组织中表达明显降低,而Trk A表达显著升高(P<0.05);二者呈显著负相关(P<0.05),Nedd4L的表达降低与Trk A表达升高均与肿瘤淋巴结转移、高TNM分期显著相关(P<0.05);在体外,下调Nedd4L表达后可显著升高Trk A蛋白的表达水平(P<0.05),而对Trk A m RNA表达无明显影响(P>0.05)。结论 Nedd4L及Trk A在老年前列腺癌组织中异常表达,Nedd4L可能通过泛素化降解癌蛋白Trk A实现其抗肿瘤作用。
