Stomach size in anorexia nervosa: A new challenge?

BACKGROUND & AIMS: Changes in stomach size may impact eating behaviour. A recent study showed gastric dilatation in restrictive eating disorders using computed tomography scans. This study aimed to describe stomach size in the standing position in women with anorexia nervosa (AN). METHODS: Women treated for AN at our institution were retrospectively included if they had undergone upper gastrointestinal radiography (UGR) after the diagnosis of AN. Two control groups (CG1 and CG2) were included, both comprising female patients: CG1 patients were not obese and underwent UGR for digestive symptoms of other aetiologies, and CG2 comprised obese individuals who had UGR before bariatric surgery. A UGR-based Stomach Size Index (SSI), calculated as the ratio of the length of the stomach to the distance between the upper end of the stomach and the top of the iliac crests, was measured in all three groups. Gastromegaly was defined as SSI >1.00. RESULTS: 45 patients suffering from AN (28 with restrictive and 17 with binge/purge subtype), 10 CG1 and 20 CG2 subjects were included in this study. Stomach Size Index was significantly higher in AN (1.27 ± 0.24) than in CG1 (0.80 ± 0.11) and CG2 (0.68 ± 0.09); p < 0.001, but was not significantly different between patients with the restrictive and binge/purge subtypes. Gastromegaly was present in 82.2% of patients with AN and not present in the control groups. In patients with AN, gastromegaly was present in 12/15 patients without digestive symptoms (80.0%) and in 25/30 patients with digestive complaints (83.3%) at time of UGR (p = 0.99). In the AN group, no significant relationship was found between SSI and body mass index. CONCLUSION: Gastromegaly is frequent in AN and could influence AN recovery. This anatomical modification could partially explain the alterations of gastric motility previously reported in AN.

Modulating Lysosomal pH through Innovative Multimerized Succinic Acid-Based Nucleolipid Derivatives.

The multimerization of active compounds has emerged as a successful approach, mainly to address the multivalency of numerous biological targets. Regarding the pharmaceutical prospect, carrying several active ingredient units on the same synthetic scaffold was a practical approach to enhance drug delivery or biological activity with a lower global concentration. Various examples have highlighted better in vivo stability and therapeutic efficiency through sustained action over monomeric molecules. The synthesis strategy aims to covalently connect biologically active monomers to a central core using simple and efficient reaction steps. Despite extensive studies reporting carbohydrate or even peptide multimerization developed for therapeutic activities, very few are concerned with nucleic acid derivatives. In the context of our efforts to build non-viral nucleolipid (NL)-based nanocarriers to restore lysosomal acidification defects, we report here a straightforward synthesis of tetrameric NLs, designed as prodrugs that are able to release no more than one but four biocompatible succinic acid units. The use of oil-in-water nanoemulsion-type vehicles allowed the development of lipid nanosystems crossing the membranes of human neuroblastoma cells. Biological evaluations have proved the effective release of the acid within the lysosome of a genetic and cellular model of Parkinson's disease through the recovery of an optimal lysosomal pH associated with a remarkably fourfold lower concentration of active ingredients than with the corresponding monomers. Overall, these results suggest the feasibility, the therapeutic opportunity, and the better tolerance of multimeric compounds compared to only monomer molecules.

iNOS is a mediator of the heat stress-induced preconditioning against myocardial infarction in vivo in the rat.

OBJECTIVE: The inducible isoform of nitric oxide synthase (iNOS) is known to be a trigger of the heat stress (HS)-induced cardioprotection. Since iNOS also appears to mediate various forms of myocardial preconditioning, the goal of this study was to investigate its role as a mediator of the HS response. METHODS AND RESULTS: Male Wistar rats were divided in six groups, subjected or not to HS (42 degrees C internal temperature, for 15 min). Twenty-four hours later, they were treated or not with either L-NAME, a non-selective inhibitor of NO synthase isoforms, or 1400W, a selective iNOS inhibitor, 10 min before being subjected to a 30-min left coronary artery occlusion followed by a 120-min reperfusion, in vivo. The infarct size (tetrazolium staining) reducing effect conferred by heat stress (from 46.0+/-1.4% in sham to 26.8+/-3.8% in HS groups) was completely abolished by both L-NAME (53.9+/-3.1%) and 1400W (51.8+/-3.3%). Additional studies using Western blot analysis demonstrated a 3.8-fold increase in myocardial iNOS protein expression 24 h after HS. CONCLUSION: These results suggest an involvement of iNOS as a mediator of the protection conferred by heat stress against myocardial ischaemia.

Endocannabinoids are implicated in the infarct size-reducing effect conferred by heat stress preconditioning in isolated rat hearts.

OBJECTIVE: We have investigated the involvement of the endocannabinoid system in the delayed cardioprotection conferred by heat stress preconditioning in the isolated rat heart. METHODS: Rats were divided into eight groups (n=7 in each group), subjected to either heat stress (42 degrees C for 15 min, HS groups) or sham anaesthesia (Sham groups). Twenty-four hours later, their hearts were isolated, retrogradely perfused, and subjected to a 30-min occlusion of the left coronary artery followed by 120 min of reperfusion. Some hearts were perfused with either SR 141716 (a cannabinoid CB(1) receptor antagonist, 1 microM), SR 144528 (a CB(2) receptor antagonist, 1 microM) or L-NAME (a NOS inhibitor, 3 microM) 5 min before ischaemia and during the ischaemic period. RESULTS: The infarct size-reducing effect conferred by heat stress (35.7+/-1.8% in Sham to 14.1+/-0.6% in HS groups) was not altered by the perfusion of SR 141716 (11.2+/-1.5%) but was abolished by both SR 144528 (36.6+/-1.6%) and L-NAME (32.0+/-4.4%). In hearts from non-heat-stressed rats, perfusion with SR 141716 (32.8+/-1.6%), SR 144528 (33.4+/-2.2%) and L-NAME (31.6+/-2.9%) had no effect on infarct size. CONCLUSION: These results suggest an involvement of endocannabinoids, acting through CB(2) receptors, and NO in the cardioprotection conferred by heat stress against myocardial ischaemia. The possible interaction between both mediators of the heat stress response remains to be determined.

Free-radical production triggered by hyperthermia contributes to heat stress-induced cardioprotection in isolated rat hearts.

1. Heat stress (HS) is known to protect the myocardium against ischaemic damage. It has been reported that reactive oxygen species (ROS) are abundantly produced during this stress. Since mechanisms triggering the HS-induced cardioprotection remain unknown, we investigated the role of ROS in the genesis of this protective phenomenon. 2. Rats were divided into four groups (n=8 in each group), subjected to either hyperthermia (42 degrees C internal temperature for 15 min) or sham anaesthesia and treated or not with N-2-mercaptopropionyl glycine (MPG), a synthetic antioxidant, 10 min before HS. Twenty-four hours later, their hearts were isolated, retrogradely perfused, and subjected to a 30-min occlusion of the left coronary artery followed by 120 min of reperfusion. Myocardial Hsp 27 and 70 expression was assessed by Western blot analysis (n=4). Cardiac activities of antioxidant enzymes (superoxide dismutase and glutathione peroxidase) were also examined (n=4). 3. Infarct-to-risk zone ratio was significantly reduced in HS (17+/-1.3%) compared to Sham (34.3+/-1.7%) hearts. This effect was abolished by MPG pretreatment (40.6+/-1.9% in HS+MPG vs. 39.8+/-2.5% in Sham+MPG hearts). This cardioprotection was associated with an enhanced Hsp 27 and 70 expression, which was not modified by MPG pretreatment. Antioxidant enzyme activities was not modified by heat stress or MPG pretreatment. 4. Free radical production following hyperthermia appears to play a role in the heat stress induced cardioprotection, independently of Hsp levels. Antioxidant enzyme activities do not seem to be implicated in this cardioprotective mechanism.