Sonodynamic Therapy: Advances and Challenges in Clinical Translation

Sonodynamic therapy (SDT) consists of the synergetic interaction between ultrasound and a chemical agent. In SDT, the cytotoxicity is triggered by ultrasonic stimuli, notably through cavitation. The unique features of SDT are relevant in the clinical context more than ever: the need for efficacy, accuracy, and safety while being noninvasive and preserving the patient's quality of life. However, despite the promising results of this technique, only a few clinical reports describe the use of SDT. The objective of this article is to provide an extensive overview of the clinical and preclinical research conducted in vivo on SDT, to identify the limitations, and to detail the developed strategies to overcome them.     

Stereotyped behaviors and compulsive complaints of pain improved by fluvoxamine in two cases of frontotemporal dementia]

There have been no systematic efforts to manage and treat patients with frontotemporal dementia (FTD), but Perry described pharmacologic interventions for some behavioral syndromes in 2001. In Perry's report, selective serotonin reuptake inhibitors (SSRI) were recommended as first choice drugs because they were well tolerated and might have an effect on some symptoms such as compulsive symptoms and eating abnormalities. Some reports were presented concerning Japanese FTD patients which showed the effect of SSRI on stereotyped behaviors and eating abnormalities by Nishikawa, et al. (2001), Ikeda, et al. (2004), and others. We describe two FTD patients with compulsive complaints of pain, one mainly on abdomen and the other on lumbar region. Fluvoxamine markedly improved their complaints of pain as well as stereotyped symptoms. Fluvoxamine might be effective for behavioral disturbances due to improvement of serotoninergic dysfunction in frontal medial and cingulated cortices, as previously described. Moreover, it has been reported that an altered response to pain stimuli, either via a loss of awareness of pain or exaggerated reaction to pain, is a specific feature of FTD, but there have been only a few reports on this feature. Fluvoxamine might be effective for compulsive complaints of pain due to improvements of compulsive symptoms and exaggerated reactions to pain in FTD, or due to the analgesic effect of SSRI. SSRI may improve compulsive complaints of pain in FTD patients.     

The Protective Role of Glutathione, Cysteine and Vitamin C against Oxidative DNA Damage Induced in Rat Kidney by Potassium Bromate

The roles of glutathione (GSH), cysteine, vitamin C., liposome-encapsulated superoxide dismutase (L-SOD) and vitamin E in preventing oxidative DNA damage and cytotoxicity in the rat kidney after administration of potassium bromate (KBrO₃) to male F344 rats were investigated by measuring 8-hydroxydeoxyguanosine (8-OH-dG), an oxidative DNA product, lipid peroxidation (LPO) levels and relative kidney weight (RKW). Combined pre- and posttreatment of animals with 2 × 800 mg/kg GSH i.p. inhibited the increase of 8-OH-dG, LPO levels and RKW caused by 80 mg/kg KBrO₃ i.p. administration. In contrast, pretreatment with 0.3 ml/kg diethylmaleate (DEM) i.p., a depletor of tissue GSH, was associated with elevation of 8-OH-dG, LPO levels and RKW after a 20 mg/kg KBrO₃ i.p. treatment, which itself caused no change. Administration of KBrO₃ itself reduced renal non-protein thiol levels, but this was inhibited by the two doses of exogenous GSH. Combined treatment with DEM and KBrO₃ lowered the non-protein thiol level in the kidney more than did DEM treatment alone. Protective effects against the oxidative damage caused by KBrO₃ were also observed for pre- and posttreatment with 400 mg/kg cysteine i.p., another sulfhydryl compound, and daily i.g. application of 200 mg/kg vitamin C for 5 days. However, no influence was evident after pre- and posttreatment with 18,000 U/kg L-SOD i.p. or daily i.g. 100 mg/kg of vitamin E for 5 days. The results suggest that intracellular GSH plays an essential protective role against renal oxidative DNA damage and nephrotoxicity caused by KBrO₃.     

TNF-alpha augments the expression of RhoA in the rat bronchus.

While nonspecific airway hyperresponsiveness (AHR) is a central feature of allergic bronchial asthma, the mechanism underlying the development of AHR is not clearly understood. We have previously demonstrated in vitro hyperresponsiveness of bronchial smooth muscle to acetylcholine (ACh) in rats that were actively sensitized and repeatedly challenged with aerosolized antigen. It has also been demonstrated that the ACh-induced, RhoA-mediated Ca(2+) sensitization is markedly augmented concomitantly with an increased expression and activation of RhoA protein in the bronchial smooth muscle of the antigen-treated rats. In the present study, we have investigated whether TNF-alpha, a proinflammatory cytokine which is involved in bronchial asthma, causes upregulation of RhoA mRNA and protein in the rat bronchus. Treatment of rat bronchial smooth muscle preparations with TNF-alpha (300 ng/ml for 24 hr) significantly shifted the concentration-response curve to ACh upwards, but did not alter the response to high K(+), when compared to that of control tissues. Levels of RhoA mRNA and protein in the TNF-alpha-treated bronchus were significantly greater than those in the control group. In conclusion, it is suggested that the augmentation of the ACh-induced contractile response evoked by TNF-alpha might be mediated by an upregulation of RhoA in rat bronchial smooth muscle.     

NPHS1两种新突变蛋白分子的细胞内分布

目的：研究NPHS1两种新突变编码蛋白在细胞内的分布与先天性肾病综合征发病机制的关系。方法：构建野生型和两种突变型NPHS1克隆，并转染至COS7细胞内，应用免疫荧光双标记的方法，分别进行细胞内及细胞表面的荧光标记，通过共聚焦显微镜对裂隙膜分子Nephrin在细胞内的分布进行研究。结果：野生型Nephrin表现为细胞内和细胞膜染色模式；V822M和C265R则主要为细胞内内质网染色模式，细胞膜着色几乎缺失。结论：突变的Nephrin蛋白由于错误折叠，不能由内质网被输送至细胞表面，这可能是先天性肾病综合征发病的机制之一。     

Solitary right ventricle metastasis by renal cell carcinoma.

A 57-year-old man with a history of renal cell carcinoma presented with presyncope. He underwent nephrectomy years earlier followed by HLA-matched allogeneic peripheral-blood stem-cell transplantation. Echocardiographic investigation revealed a solitary right ventricle mass without contiguous vena caval or right atrial involvement. The mass was pathologically confirmed to be metastatic carcinoma in the right ventricular cavity. This case highlights the need to consider an underlying neoplastic syndrome in patients presenting isolated right ventricle mass by echocardiography.