Risperidone-induced metabolic dysfunction is attenuated by Curcuma longa extract administration in mice.

Antipsychotics, such as risperidone, increase food intake and induce alteration in glucose and lipid metabolism concomitantly with overweight and body fat increase, these biological abnormalities belong to the metabolic syndrome definition (high visceral adiposity, hypertriglyceridemia, hyperglycemia, low HDL-cholesterol and high blood pressure). Curcumin is a major component of traditional turmeric (Curcuma longa) which has been reported to improve lipid and glucose metabolism and to decrease weight in obese mice. We questioned the potential capacity of curcumin, contained in Curcuma longa extract (Biocurcuma™), to attenuate the risperidone-induced metabolic dysfunction. Two groups of mice were treated once a week, for 22 weeks, with intraperitoneal injection of risperidone (Risperdal) at a dose 12.5 mpk. Two other groups received intraperitoneal injection of the vehicle of Risperdal following the same schedule. Mice of one risperidone-treated groups and of one of vehicle-treated groups were fed a diet with 0.05% Biocurcuma™ (curcumin), while mice of the two other groups received the standard diet. Curcumin limited the capacity of risperidone to reduce spontaneous motricity, but failed to impede risperidone-induced increase in food intake. Curcumin did not reduce the capacity of risperidone to induce weight gain, but decreased visceral adiposity and decreased the risperidone-induced hepatomegaly, but not steatosis. Furthermore, curcumin repressed the capacity of risperidone to induce the hepatic over expression of enzymes involved in lipid metabolism (LXRα, FAS, ACC1, LPL, PPARγ, ACO, SREBP2) and decreased risperidone-induced glucose intolerance and hypertriglyceridemia. Curcumin decreased risperidone-induced increases in serum markers of hepatotoxicity (ALAT, ASAT), as well as of one major hepatic pro-inflammatory transcription factor (NFκB: p105 mRNA and p65 protein). These findings support that nutritional doses of curcumin contained in Curcuma longa extract are able to partially counteract the risperidone-induced metabolic dysfunction in mice, suggesting that curcumin ought to be tested to reduce the capacity of risperidone to induce the metabolic syndrome in human.

Proton MR Spectroscopy and Diffusion MR Imaging Monitoring to Predict Tumor Response to Interstitial Photodynamic Therapy for Glioblastoma.

Despite recent progress in conventional therapeutic approaches, the vast majority of glioblastoma recur locally, indicating that a more aggressive local therapy is required. Interstitial photodynamic therapy (iPDT) appears as a very promising and complementary approach to conventional therapies. However, an optimal fractionation scheme for iPDT remains the indispensable requirement. To achieve that major goal, we suggested following iPDT tumor response by a non-invasive imaging monitoring. Nude rats bearing intracranial glioblastoma U87MG xenografts were treated by iPDT, just after intravenous injection of AGuIX® nanoparticles, encapsulating PDT and imaging agents. Magnetic Resonance Imaging (MRI) and Magnetic Resonance Spectroscopy (MRS) allowed us an original longitudinal follow-up of post-treatment effects to discriminate early predictive markers. We successfully used conventional MRI, T2 star (T2*), Diffusion Weighted Imaging (DWI) and MRS to extract relevant profiles on tissue cytoarchitectural alterations, local vascular disruption and metabolic information on brain tumor biology, achieving earlier assessment of tumor response. From one day post-iPDT, DWI and MRS allowed us to identify promising markers such as the Apparent Diffusion Coefficient (ADC) values, lipids, choline and myoInositol levels that led us to distinguish iPDT responders from non-responders. All these responses give us warning signs well before the tumor escapes and that the growth would be appreciated.

Focal laser interstitial thermotherapy (LITT) at 980 nm for prostate cancer: treatment feasibility in Dunning R3327-AT2 rat prostate tumour.

OBJECTIVE: To examine the feasibility and reproducibility of laser interstitial thermotherapy (LITT) as a minimally invasive method for the treatment of prostate cancer. MATERIALS AND METHODS: Heterotopic tumours of prostatic adenocarcinoma (Dunning R3327-AT2) were induced in 10 male Copenhagen rats. After preoperative magnetic resonance imaging (MRI), a 10-mm cylindrical diffusing fibre developed by our research department was inserted under ultrasonographic guidance into the tumour. LITT was performed with a 980-nm diode laser (power 5 W) for 75 s (fluence rate of 1145 J/cm(2)). Non-enhanced T2-weighted and dynamic gadolinium-enhanced T1-weighted MRI examinations were performed at baseline, 1 and 48 h after the procedure and correlated with histological findings. RESULTS: The necrosis lesions induced by LITT were visible on MRI. The mean (SD) ellipsoid necrosis volumes were 0.748 (0.075) mL at 1 h and 0.982 (0.052) mL at 48 h after the LITT procedure, and significantly different (P < 0.001). Histological analysis showed a strong correlation (r = 0.87) with the mean necrosis volume obtained by MRI at 48 h after LITT. CONCLUSIONS: In a prostatic adenocarcinoma model, 980-nm LITT induces reproducible necrosis volumes. Further characterization of the response to LITT in an animal model and in human tissues will be important in establishing the efficacy of the procedure for prostate cancer focal therapy.

[Blood flow assessment with magnetic resonance imaging after 1.9 µm diode laser assisted arterial micronastomoses]. / Évaluation du flux sanguin par imagerie en résonance magnétique fonctionnelle après anastomoses artérielles assistées par laser diode 1,9µm.

INTRODUCTION: The most important factor for successful free-flap transfer and replantations is a well-executed anastomosis. The aim of this study is to assess blood flow after laser assisted arterial microanastomosis (LAMA) using a 1.9 µm diode laser. MATERIALS AND METHODS: LAMA was performed on a series of 10 carotidis on Wistar rats. Two 10/0 stay sutures and a standard laser tissue welding technique (λ: 1.9 µm; power: 120mW) were used. Similarly, a series of 10 conventional arterial anastomosis were performed (CSMA). For the two groups, contralateral non-operated carotidis were used as control. A positioning sequence, an anatomical sequence, an angiographic sequence and a flow sequence were performed 1 day after operation and then after 1, 4 and 8 weeks. RESULTS: The arterial patency rate was 100% at the time of surgery. The mean clamping time was 7.2 min in the LAMA group compared to 10.7 min in the CSMA group. In the angiographic sequence, there were no aneurysms in both groups for all observation periods. At postoperative day 1, the mean loss of blood flow at the level of anastomosis in the LAMA group was 6% compared with 14% in the CSMA group. After 1, 4 and 8 weeks, there was an unhooking of the blood flow in the CSMA group: the loss of blood flow was 23%, 27% and 31% respectively, compared with 10%, 12% and 13% in the LAMA group. Moreover, one case of thrombosis was observed in the CSMA group after 1 week. CONCLUSION: The flow-MRI emphasizes that 1.9 µm diode laser assisted microvascular anastomosis appears to be a consistent and reliable technique. These results show that 1.9 µm diode laser assisted microvascular anastomosis has potential for further development in the near future.