E. Trabucchi

Treatment of morbid obesity by intraparietogastric administration of botulinum toxin: a randomized, double-blind, controlled study

Objective:The stomach is the main target organ for bariatric surgery, but no medical treatment has been developed to increase satiety and decrease food intake via gastric pathways. The aim of our study was to investigate whether or not the intraparietogastric administration of botulinum toxin A (BTX), able to modify the motility patterns of the stomach, could be useful for treatment of obesity.Design:Double blind controlled study.Subjects:Twenty-four morbidly obese patients (mean weight (s.e.m.) 116.1±4.89 kg, mean body mass index (BMI) 43.6±1.09 kg/m2) were blindly randomized to receive 200 IU BTX or placebo into the antrum and fundus of the stomach by intraparietal endoscopic administration.Measurements:We evaluated weight loss, BMI changes, satiety score, the maximal gastric capacity for liquids and the gastric emptying time (octanoic acid breath test).Results:The two groups were homogeneous for anthropometric characteristics. Eight weeks after treatment, BTX patients had significantly higher weight loss (11±1.09 vs 5.7±1.1 kg, P<0.001) and BMI reduction (4±0.36 vs 2±0.58 kg/m2, P<0.001) and a higher satiety score on a visual analogic scale (7.63±0.38 vs 4.72±0.44, P<0.001) than controls. Furthermore, BTX patients showed a significantly greater reduction in maximal gastric capacity for liquids (266.6±48 vs 139±31, P<0.001) and a greater prolongation in gastric emptying time (+18.93±8 vs −2.2±6.9 min, P<0.05). No significant side effects or neurophysiologic changes were found.Conclusions:Topical intragastric BTX was effective in reducing food intake and body weight in morbidly obese patients.

The mechanisms of blood vessel closure in humans by the application of ultrasonic energy.

BackgroundThe use of the ultrasonically activated scalpel (UAS) for vessel closure has attained widespread acceptance in many surgical fields. The aim of our study was to investigate the electron microscopic changes to the blood vessels after the application of UAS.MethodsWe collected 10 arterial and 10 venous segments from vessels that had previously been closed by UAS during abdominal operations. The samples were then prepared for ultramicroscopic analysis Pathological changes in the lumen and the three wall layers of the blood vessel were examined under scanning and transmission electron microscopy.ResultsAll of the vessel segments showed similar changes: the presence of a blood clot, endothelial cell condensation, coagulative necrosis of the wall, and charring of the vessel at its tip. The edge of the cut vessel were closed by the coagulation bond, which was tied up by collagen fibrils escaped from denaturation.ConclusionWhen ultrasonic energy is applied to tissues, it changes their structure so as to make a new extracellular matrix.

Different Effects of Vertical Banded Gastroplasty and Roux-en-Y Gastric Bypass on Meal Inhibition of Ghrelin Secretion in Morbidly Obese Patients

A decrease in ghrelin plasma levels in morbidly obese patients subjected to bariatric surgery has been considered to help increase body weight loss. Contradictory results have been described after Roux-en-Y gastric bypass (RYGBP), and no study to date has compared RYGBP and vertical banded gastroplasty (VBG), the two main operations performed in the United States. We investigated the effects of RYGBP (10 patients) and VBG (12 patients) on basal and postmeal ghrelin plasma levels in 22 morbidly obese patients (20 F and 2 M), mean age 42.1 ± 3.7 years, mean weight 115 ± 3.9 kg, mean body mass index (BMI) 43.5 ± 1.7. Before surgery and after a 20% reduction in BMI, ghrelin concentrations (pg/mL; radioimmunoassay [RIA], DRG Diagnostics, Germany) were measured in all patients 45 min before and for 3 h after a standard liquid meal (Osmolite RTH solution, 500 mL, 504 kcal). The results were expressed as mean ± SD. Differences between times and groups were evaluated by Students t-test and one-way analysis of variance (ANOVA). We found that basal ghrelin plasma levels were reduced after RYGBP (to 73.1 ± 6 pg/mL, p <. 05) but increased after VBG (to 172 ± 26 pg/mL, p <. 0009). After a standard liquid meal, ghrelin plasma levels decreased significantly over 1 h in VBG patients, whereas they remained unchanged in RYGBP patients. Since these results were obtained under the same metabolic and anthropometric conditions, we conclude that RYGBP acts through permanent inhibition of ghrelin secretion, whereas VBG merely restores the mechanisms of ghrelin regulation by nutrients.

Late rejection of the mesh after laparoscopic hernia repair.

Abstract. We report the first case of late rejection of a mesh after laparoscopic hernia repair. It occurred in a 48-year-old man who had had a laparoscopic hernia repair by transabdominal preperitoneal approach 3 years earlier. The most characteristic finding was the slow development of a firm mass in the right groin, without pain or fistula. At admission 3 months later, US and CT scans demonstrated a necrotic mass extending into both iliac fossa. The mass was approached through a midline incision. Pus was taken for microscopic examination (negative), and the mesh was removed, along with several staples. Ultramicroscopic examination of the mesh showed breakdown of the fibers, collagen reduction, and no chronic inflammatory cells. No infectious cause of inflammation was identified.

Towards ideal magnetofluorescent nanoparticles for bimodal detection of breast-cancer cells

An increasing number of novel molecular markers based on nanomaterials for tumor diagnostics have been developed in recent years. Many efforts have focused on the achievement of site-targeted bioconjugated nanoparticles. In contrast, the mechanisms of toxicity, endocytosis, and degradation pathways are still poorly understood, despite their primary importance for clinical translation. In this study, three different model nanoscale magnetofluorescent particle systems (MFNs) are designed and fabricated. These nanoparticles are evaluated in terms of size, morphology, zeta potential, fluorescence efficiency, capability of enhancing T(2) relaxivity of water protons, and stability. Accordingly, two are developed and the mechanism of internalization, the intracellular fate, and the toxicity in MCF-7 adenocarcinoma cells are studied. Besides the well-documented size effect, the anionic charge seems to be a crucial factor for particle internalization, as MFN penetration through the cell membrane could be modulated by surface charge. Ultrastructural analysis of transmission electron micrographs combined with evidence from confocal microscopy reveals that MFNs are internalized by clathrin-mediated endocytosis and macropinocytosis. Moreover, MFNs are found in EEA1-positive endosomes and in lysosomes, indicating that they follow a physiological pathway of endocytosis. Magnetorelaxometric analysis demonstrates that MFNs enable the detection of 5 x 10(5) cells mL(-1) after treatment with particle dosages as low as 30 microg mL(-1). Hence, MFNs appear to be a valuable and safe bimodal contrast agent that can be developed for the noninvasive diagnosis of breast cancer.

Angiogenic Effects of Suture Biomaterials

Angiogenesis is a limiting step of inflammation and wound healing. Although laboratory tests for the evaluation of the angiogenetic effects of biomaterials are available, no investigations have been performed. In this study we examine the angiogenetic effect of suture biomaterials in the rat mesenteric window model. Absolute controls had laparotomy only, controls had mesenteric window wounding, test groups had the insertion of either a thread of collagen, polyglactin 910, polyglycolic acid salt, silk or of a titanium clip. We considered the percentage area of the mesenteric window covered by neovessels. After 7 days, negligible angiogenesis was found in absolute controls, significant angiogenesis in controls, collagen, polyglactin 910 and polyglycolic acid salt treated rats, without differences between treatments. A significant increase of angiogenesis in comparison to the control group was found in rats treated with silk and titanium. Ultramicroscopy of the neovessels showed specific changes of their architecture in titanium-treated rats. In conclusion, angiogenesis during wound healing is differently influenced by the suture material used. Silk and titanium stimulated angiogenesis in a different way.

Histological and ultrastructural evaluation of extracorporeal shock wave lithotripsy-induced acute renal lesions: preliminary report.

Biopsy material taken from kidneys of 14 patients with renal stones before performing extracorporeal shock wave lithotripsy (ESWL) and an average of 15 days after was examined histologically and ultrastructurally. In the post-ESWL specimens, light microscopy revealed edema and extravasation of urine and blood into the interstitial spaces, blocking of cortical tubules by hemorrhagic streaks and widespread dilatation of the veins, with signs of endothelial destruction and partial organization of thrombi. By using the electron microscope, abnormalities of the endothelium and glomerular epithelium, hemosiderin accumulations in the tubular cells and small linear patches of fibrosis at the corticomedullary junction and in the cortical interstitial spaces were seen. This preliminary report indicates that renal damage can be shown soon after ESWL on histological and ultrastructural studies and that the lesions observed can be either reversible or permanent.

Femtomolar detection of autoantibodies by magnetic relaxation nanosensors

The development of nanosystems applied to rapid and sensitive measurement of biomarkers in fluid samples is a current major goal in diagnostic biomedicine. In this article, we report the accurate and reliable detection of anti-HSA (human serum albumin) antibodies by protein-functionalized magnetic nanospherical probes due to the reversible alteration of their microaggregation state induced by protein antibody-specific interaction, sensed as changes in the T(2) relaxation time of surrounding water molecules. Once the optimal parameters were adjusted, the method proved to be very sensitive, providing concentration- and time-dependent responses. Furthermore, we demonstrate that the developed immunoassay is able to quantitatively determine the biomarker concentration from T(2) linear correlation, thereby supplying a rapid, yet accurate, assay with sensitivity in the femtomolar range. The high susceptibility and stability of these magnetic nanoparticles, as well as their accessible synthetic preparation, make these nanosensors a promising new tool for versatile and effective medical diagnostics.

Ibuprofen-arginine generates nitric oxide and has enhanced anti-inflammatory effects.

Ibuprofen, a chiral non-steroidal anti-inflammatory drug chemically related to fenoprofen and naproxen, has moderate but definite anti-inflammatory, analgesic and antipyretic properties, with considerably less gastrointestinal adverse effect than other drugs in the same family. Currently available in the market are preparations in which bioavailability of ibuprofen is increased by salification with various salts. We have investigated the pharmacological properties of one such salt, ibuprofen-arginine, of biological interest because l-arginine acts as substrate of the nitric oxide (NO) synthesising enzymes. Using epithelial HeLa cells expressing the endothelial NO synthase we show that ibuprofen-arginine releases NO and that this NO protects against the cytotoxic apoptogenic effects of staurosporine. We also found that ibuprofen-arginine is endowed with enhanced anti-inflammatory effects with respect to ibuprofen, as shown by reduced hind paw oedema, neutrophil infiltration and chondrocyte apoptosis in collagen-induced mouse arthritis, a model of chronic inflammation. NO has pleiotropic beneficial effects that may contribute to limit inflammation and anti-inflammatory compounds able to release NO display higher efficacy than the parent drugs in defined clinical settings. Our results open the possibility that NO generation contributes to the enhanced anti-inflammatory effects of ibuprofen-arginine vs. ibuprofen, suggesting co-administration of anti-inflammatory drugs and arginine as an additional way to exploit the beneficial effects of NO.

Effects of intramural administration of Botulinum Toxin A on gastric emptying and eating capacity in obese patients

BACKGROUND Intraparietal gastric administration of Botulinum Toxin A has been studied in open trials to induce satiety and increase weight loss of obese patients with contradictory results. In previous studies only the antrum was the target for Botulinum Toxin A, whereas the fundus, which exerts important activity on gastric accommodation, was excluded. In this study we report the effects of injection into both gastric regions on solid gastric capacity and emptying of the stomach. MATERIALS AND METHODS In this study we extended our previous investigations to include 30 obese patients who received Botulinum Toxin A (120 U into the antrum and 80 U into the fundus) or saline by intraparietal endoscopic injection. The two groups were homogeneous for age, gender, body weight and body mass index. Body weight and body mass index, solid gastric emptying (T(1/2) and T(lag) at the octanoic acid breath test) and maximal gastric capacity for solids (kcal) were determined before injection and 2 months later. The results were expressed as mean values (S.E.M.). t-Test or Wilcoxon test was used for statistical analysis, p<0.05 being considered significant. RESULTS Both treatments induced a significant reduction of body weight and body mass index but Botulinum Toxin A exerted a significantly greater effect (body weight -11.8+/-0.9 kg vs. -5.5+/-1.1 kg, p<0.0002; body mass index -4.1+/-0.2 vs. -2.2+/-0.4, p<0.001). The maximal gastric capacity for solids was also reduced by both Botulinum Toxin A and placebo, the former being significantly more effective (679+/-114 kcal vs. 237+/-94 kcal, p<0.008). Botulinum Toxin A also significantly increased T(1/2) from 83.4+/-3.9 to 101.6+/-9.9 min, p<0.03) but T(lag) was unchanged. Placebo had no effect on either of these parameters. CONCLUSIONS Our results demonstrated that Botulinum Toxin A makes weight loss easier in obese patients. It acts by increasing the solid gastric emptying time and reducing the solid eating capacity of the stomach.