Study of gold nanoparticles for mammography diagnostic and radiotherapy improvements.

AIM: A study on the possibility to use gold nanoparticles in mammography, both for a better image diagnostics and radiotherapy, is presented and discussed. We evaluate quantitatively the increment of dose released to the tumor enriched with Au-NPs with respect to the near healthy tissues, finding that for X-rays the increase can reach two orders of greater intensity. BACKGROUND: Gold nanoparticles continue to be investigated for their potential to improve existing therapies and to develop novel therapies. They are simple to obtain, can be functionalized with different chemical approaches, are stable, non-toxic, non-immunogenic and have high permeability and retention effects in the tumor cells. The possibility to use these for breast calcified tumors to be better treated by radiotherapy is presented as a possible method to destroy the tumor. MATERIALS AND METHODS: The nanoparticles can be generated in water using the top-down method, should have a size of the order of 10-20 nm and be treated to avoid their coalescence. Under diagnostic X-ray monitoring, the solution containing nanoparticles can be injected locally inside the tumor site avoiding injection in healthy tissues. The concentrations that can be used should be of the order of 10 mg/ml or higher. RESULTS: An enhancement of the computerized tomography diagnostics using 80-150 keV energy is expected, due to the higher mass X-ray coefficient attenuation with respect to other contrast media. Due to the increment of the effective atomic number of the biological tissue containing the gold nanoparticles, also an improvement of the radiotherapy effect using about 30 keV X-ray energy is expected, due to the higher photoelectric cross sections involved. CONCLUSIONS: The study carried out represents a feasibility proposal for the use of Au-nanoparticles for mammographic molecular imaging aimed at radiotherapy of tumor nodules but no clinical results are presented.

Gold Nanoparticles by Laser Ablation for X-Ray Imaging and Protontherapy Improvements.

BACKGROUND: Gold nanoparticles, 5-20 nm in diameter, were generated with a pulsed Nd: YAG laser at 1010 W/cm2 at solution concentrations ranging between 1-100 mg/ml. The incremental X-ray contrast imaging using gold nanoparticles was investigated and measured. The study was performed with the aim to enhance the massive absorption coefficient of X-ray radiation in the tumor for medical image quality and to improve traditional X-ray radiotherapy or proton therapy. A simulation of proton therapy improvement was conducted using a human ocular melanoma model, placed 3 cm behind the eye lens, and testing 60 MeV protons. Calculations suggest that the local injection of a solution containing Au-NPs may increase the proton energy released in the tumor above 50%, with the dose in the surrounding tissues leading to an increased probability of tissue healing. A discussion on recent patents in the ambit of the preparation and use of Au nanoparticles in medical imaging and therapy is presented. METHODS: Au nanoparticles were characterized using optical absorbance, X-ray fluorescence, SEM, and TEM microscopies. Biocompatible nanoparticle solutions were injected intravenously into tail veins of mice followed by X-ray imaging using 20-45 keV photons to evaluate the uptake and the clearance by different organs of the nanoparticles. RESULTS: Diagnostic X-ray images of mice in which the Au-NPs were injected showed high spatial resolution contrast of different organs having high up-take. A calculation of the dose released by X-rays, electrons and protons to the tumor site demonstrates that an increment of the order of 50% can be obtained using adapt solution concentration. CONCLUSION: The use of Au-NPs in biocompatible solutions injected in living organism permits their blood transport up to different organs. The NPs can be employed as contrast medium to enhance the medical image resolution and to prepare the cancer tissues to be exposed to ionization radiations in order to enhance the dose released to the tumor cells. This effect permits to reduce the total dose given to the patient and to increase the dose released to the tumor cells with respect to healthy ones.

Re-emergence of diabetes after gastric bypass in patients with mid- to long-term follow-up.

BACKGROUND: Studies have shown that type 2 diabetes (T2DM) improves or resolves shortly after Roux-en-Y gastric bypass (RYGB). Few data are available on T2DM recurrence or the effect of weight regain on T2DM status. METHODS: A review of 42 RYGB patients with T2DM and >or=3 years of follow-up and laboratory data was performed. Postoperative weight loss and T2DM status was assessed. Recurrence or worsening was defined as hemoglobin A1c >6.0% and fasting glucose >124 mg/dL and/or medication required after remission or improvement. Patients whose T2DM recurred or worsened were compared with those whose did not, and patients whose T2DM improved were compared with those whose T2DM resolved. RESULTS: T2DM had either resolved or improved in all patients (64% and 36%, respectively); 24% (10) recurred or worsened. The patients with recurrence or worsening had had a lower preoperative body mass index than those without recurrence or worsening (47.9 versus 52.9 kg/m2; P = .05), regained a greater percentage of their lost weight (37.7% versus 15.4%; P = .002), had a greater weight loss failure rate (63% versus 14%; P = .03), and had greater postoperative glucose levels (138 versus 102 mg/dL; P = .0002). Patients who required insulin or oral medication before RYGB were more likely to experience improvement rather than resolution (92% versus 8%, P

Markers of bone and calcium metabolism following gastric bypass and laparoscopic adjustable gastric banding.

BACKGROUND: Several studies have suggested that morbid obesity is associated with vitamin D deficiency and elevated parathyroid hormone (PTH). Studies have also suggested that there is an increase in vitamin D deficiency, bone resorption, and elevated PTH after gastric bypass surgery. Few studies have evaluated markers of bone and calcium metabolism after laparoscopic adjustable gastric banding or compared these results to those after gastric bypass. METHODS: Data on all patients undergoing primary gastric bypass (GBP; n = 979) and laparoscopic adjustable gastric banding (LAGB; n = 269) procedures at a tertiary-referral center from June 1996 through March 2005 were reviewed from a prospective database. Only patients with 25OH vitamin D levels available were included in this study (n = 534; GBP = 403, LAGB = 131). All patients were advised to take at least 1,200 mg calcium and 800-1,200 IU of vitamin D daily before and subsequent to their operation. Markers for bone metabolism [25OH Vitamin D, corrected serum calcium, alkaline phosphatase (AP), and PTH] were evaluated preoperatively and 3, 6, 12, and 24 months postoperatively. An analysis of variance and chi-square were performed to determine differences between the operative groups. Linear regression analysis was performed to evaluate the relationship between preoperative body mass index (BMI) and 25OH vitamin D and PTH levels and between percent excess weight loss and 25OH vitamin D and PTH after surgery. RESULTS: Sixty-four percent of all patients presented with vitamin D deficiency (<20 ng/ml) and 14% presented with elevated PTH preoperatively. Mean 25OH vitamin D levels and AP levels increased significantly after GBP surgery (vitamin D, 17 to 25 ng/ml 12 months post-op; AP, 80 to 90 IU/L 24 months post-op). Corrected calcium levels remained within normal limits and showed no change over time after both procedures. AP levels significantly increased from 76 IU/l preoperatively to 82 IU/l 6 months after LAGB surgery and then decreased to 59 IU/l 24 months after LAGB surgery. Linear regression analysis of preoperative vitamin D, PTH, and BMI values showed a significant positive relationship between initial BMI and PTH (r = 0.29) and a significant negative relationship between vitamin D and initial BMI (r = -0.19). A significant positive linear relationship between vitamin D and percent excess weight loss was evident 12 and 24 months after GBP surgery (r = 0.39 and 0.57, respectively). A negative relationship was evident between PTH and vitamin D 6 months after GBP surgery (r = -0.35) and 12 months after LAGB surgery (r = -0.61). CONCLUSIONS: These findings suggest that morbid obesity is associated with vitamin D deficiency, and elevated PTH and with adequate supplementation, GBP, and particularly LAGB, patients can improve their bone metabolism abnormalities related to obesity. Furthermore, adequate supplementation for GBP patients may attenuate the increased risk for bone loss associated with malabsorption from the bypass.

Differential effects of gastric bypass and banding on circulating gut hormone and leptin levels.

OBJECTIVE: To quantify plasma concentrations of hormones that regulate energy homeostasis in order to establish possible mechanisms for greater weight loss after Roux-en-Y gastric bypass (RYGBP) compared with gastric banding (BND). RESEARCH METHODS AND PROCEDURES: Four groups of women were studied: lean (n = 8; mean BMI, 21.6 kg/m2); BND (n = 9; BMI, 35.8; 25% weight loss), RYGBP (n = 9; BMI, 34.2; 36% weight loss), and controls matched for BMI to the surgical groups (n = 11; BMI, 34.4). RESULTS: Fasting total peptide YY (PYY) and PYY(3-36) immunoreactivity were similar among all groups, but the postprandial response in the RYGBP group was exaggerated, such that 30 minutes after the meal, total and PYY(3-36) levels were 2- to 4-fold greater compared with all other groups. Maximal postprandial suppression of total ghrelin was blunted in the BND group (13%) compared with RYGBP (27%). Postprandial suppression of octanoylated ghrelin was also less in BND (29%) compared with RYGBP (56%). Fasting insulin was lower in RYGBP (6.6 microU/mL) compared with BND (10.0 microU/mL). Compared with lean controls, leptin concentrations were significantly higher in BND but not in RYGBP. There was a greater increase in post-meal satiety in the RYGBP group compared with BND and overweight controls. DISCUSSION: The differences between RYGBP and BND subjects in postprandial concentrations of PYY and ghrelin would be expected to promote increased satiety and earlier meal termination in RYGBP and may aid in greater weight loss. The differences in insulin and leptin concentrations associated with these procedures may also reflect differences in insulin sensitivity and energy partitioning.

Effects of Roux-en-Y gastric bypass surgery on fasting and postprandial concentrations of plasma ghrelin, peptide YY, and insulin.

To help understand the mechanisms by which weight loss is maintained after Roux-en-Y gastric bypass (RYGBP), we measured circulating concentrations of total and bioactive octanoylated ghrelin, peptide YY (PYY), glucose, and insulin in the fasted state and in response to a liquid test meal in three groups of adult women: lean (n = 8); weight-stable 35 +/- 5 months after RYGBP (n = 12; mean body mass index, 33 kg/m(2)); and matched to the surgical group for body mass index and age (n = 12). Fasting plasma total ghrelin levels were nearly identical between RYGBP (425 +/- 54 pg/ml) and the matched controls (424 +/- 28 pg/ml) and highest in lean controls (564 +/- 103 pg/ml). The response to the test meal was comparable between lean and RYGBP groups, with 27% and 20% maximal suppression, respectively, whereas the magnitude of suppression was significantly diminished in the matched controls (17%) compared with the lean group. Fasting levels of octanoylated ghrelin were highest in the lean controls, 220 +/- 36 pg/ml vs. 143 +/- 27 in the RYGBP group (P = 0.05) and 127 +/- 12 pg/ml in the matched controls (P < 0.05). The magnitude of maximal postmeal suppression of octanoylated ghrelin was more marked than with total ghrelin, but similar among groups, ranging from 44-47%. In response to the test meal, there was an early exaggerated rise in PYY in the RYGBP group, such that the peak PYY concentration was 163 +/- 24 pg/ml compared with 58 +/- 17 (P < 0.01) and 77 +/- 23 (P < 0.05) in the matched and lean controls, respectively; area under the curve at 90 min was significantly greater compared with both control groups. Leptin and fasting insulin concentrations and homeostasis model of assessment insulin resistance indices were nearly identical between lean and RYGBP subjects and significantly higher in the body mass index-matched controls. In summary, the absence of a compensatory increase in ghrelin concentrations that usually occurs with diet-induced weight loss, and the exaggerated postprandial PYY response after RYGBP, may contribute to weight loss and to the ability of an individual to maintain weight loss after this surgical procedure.