An update in the management of obesity: the weight of CNS targets

Obesity is one of the most important and disturbing global epidemic that affects humans, with more than 2 billion people overweight and 700 million obese predicted for 2015 by the World Health Organization. Obesity treatment represents then one of the most exciting challenges for the academic researchers and the pharmaceutical industry. But to date, this community failed to develop safe and effective treatments with a good risk/benefit profile. Indeed, most of the drugs previously used as anti-obesity agents have been withdrawn from the market for safety issues, and therapeutic options in form of a medication are currently very limited. This last decade however, new advances in our understanding of central pathways controlling food intake, body weight and energy homeostasis have led to the discovery of new molecular targets that could provide interesting options in the fight against obesity. This review aims to be an overview of the new patents exploiting the anorexigenic properties of the central catabolic pathways or aimed at blocking the orexigenic effects of the anabolic pathways, in the hope to develop new anti-obesity drugs.     

The level of associated depression and anxiety traits improves during weight regain in eating disorder patients

We assessed whether re-nutrition and weight gain have an influence on comorbid depression and anxiety in patients hospitalised for chronic eating disorders (ED). Seventy-five inpatients agreed to participate by completing the Eating Attitudes Test (EAT-40), the Beck Depression Inventory (BDI-13), and the State-Trait Anxiety Inventory (STAI-Y) before, during and after three months of treatment. Patients suffering from either anorexia nervosa or bulimia nervosa successfully regained weight during treatment. This weight gain was accompanied by statistically significant reductions in ED symptoms. Anxiety and, to a lesser extent, depressive symptoms diminished, but remained at pathological levels, with between diagnostic subtype differences. Improvement of depressive (r=0.77) and anxiety (r=0.64) levels were significantly (p<0.001) and positively correlated with the reduction of eating attitudes (EAT). These results are discussed in the context of re-orienting the therapeutic strategies aimed at reducing emotional suffering in patients with ED.     

Congenital isolated midline sinus of the upper lip: clinical and embryological approaches.

OBJECTIVES: Congenital sinuses or fistulas of the lip are uncommon malformations, yet true medial upper-lip fistulas (MULFs) are extremely rare. We present a new case of congenital upper-lip fistula located in the midline of the philtrum of an 8-month-old girl. INTERVENTION: Complete surgical removal was performed with a combined extra- and intraoral approach. Histological examination revealed that the fistula was lined by squamous epithelium with sebaceous and mucous glands and hair follicles. RESULTS: Several embryological hypotheses have been proposed concerning these anomalies. This article reexamines and discusses major embryological theories on pathogenesis of sinuses or fistulas of the upper lip. We propose that early ectodermal inclusion events may occur in the medial fusion area during formation of the intermaxillary process. This embryological approach is highly concordant with our recent hypothesis on nasal dermoid sinus cysts (NDSCs) pathogenesis, in which we proposed an embryological hypothesis with early ectodermal inclusion phenomenon in the midline suture area to explain NDSCs pathogenesis. CONCLUSIONS: Common early ectodermal inclusion phenomena could be involved in both NDSCs and MULFs pathogenesis.     

Benign nontraumatic osteolytic vertebral collapse simulating malignancy

This study described the imaging features of a distinctive pattern of biopsy-proven benign non-traumatic vertebral collapse (VC) that can mimic malignancy. Among 240 patients referred with painful VC over a 10-year period, we retrospectively selected 15 cases of benign VC which simulated malignancy, due to cortical bone destruction on radiographs. The diagnosis of benign origin was documented by percutaneous biopsy and 12-months of follow-up. Radiographs, CT and MR images of the spine were reviewed. Findings suggestive of malignancy included destruction involving the anterolateral cortex, posterior cortex and pedicles of the vertebral body (46%,15% and 15% respectively) at CT, epidural soft-tissue masses on CT (23%) and MR images (21%), and diffuse low signal-intensity (SI) of the vertebral body (50%) and pedicles (79%) on T1-weighted images. Features suggestive of a benign origin included an intravertebral vacuum phenomenon on radiographs and CT (13%), fracture lines within the vertebral body (92%) or pedicles (62%) at CT and presence an intravertebral area of high SI on T2-weighted images (93%). Benign non-traumatic osteolytic VC can simulate malignancy on radiographs. The features, above mentioned on CT and MR suggestive of a benign VC, are useful in interpreting biopsy results of such lesions and avoiding unnecessary repeat biopsy.     

CT-guided percutaneous laser photocoagulation of osteoid osteomas of the hands and feet

Percutaneous local ablation of osteoid osteoma has largely replaced surgery, except in the small bones of the hands and feet. The objective of this study was to describe the technical specificities and results of computed tomography (CT)-guided percutaneous laser photocoagulation in 15 patients with osteoid osteomas of the hands and feet. We retrospectively examined the medical charts of the 15 patients who were treated with CT-guided percutaneous laser photocoagulation therapy at our institution between 1994 and 2004. The 15 patients had a mean age of 24.33 years. None of them had received any prior surgical or percutaneous treatment for the osteoid osteoma. The follow-up period was 24 to 96 months (mean, 49.93). The pain resolved completely within 1 week. Fourteen patients remained symptom-free throughout the follow-up period; the remaining patient experienced a recurrence of pain after 24 months, underwent a second laser photocoagulation procedure, and was symptom-free at last follow-up 45 months later. No adverse events related to the procedure or to the location of the tumor in the hand or the foot were recorded. CT-guided percutaneous laser photocoagulation is an alternative to surgery for the treatment of osteoid osteomas of the hands and feet.     

BEL-2, an Extended-Spectrum β-Lactamase with Increased Activity toward Expanded-Spectrum Cephalosporins in Pseudomonas aeruginosa

A Pseudomonas aeruginosa isolate recovered in Belgium produced a novel extended-spectrum ß-lactamase, BEL-2, differing from BEL-1 by a single Leu162Phe substitution. That modification significantly altered the kinetic properties of the enzyme, increasing its affinity for expanded-spectrum cephalosporins. The bla_BEL-2 gene was identified from a P. aeruginosa isolate clonally related to another bla_BEL-1-positive isolate.Extended-spectrum ß-lactamases (ESBLs), such as TEM, SHV, PER, VEB, GES, and more recently, CTX-M variants, are reported increasingly to be found in Pseudomonas aeruginosa in various areas (1, 2, 7, 8, 10-12, 15, 17, 21, 23, 27, 28, 30). The BEL-1 ß-lactamase, distantly related to other ESBLs, was identified from a P. aeruginosa isolate from Roeselare, Belgium, which interestingly shows resistance to ticarcillin and ceftazidime but only reduced susceptibility to piperacillin, cefepime, cefpirome, and aztreonam (24). The bla_BEL-1 determinant was found as a gene cassette in the chromosome-borne class 1 integron, In120, that includes other resistance genes (aacA4, aadA5, and smr2) and that was part of a Tn1404-type transposon structure (24). Very recently, Bogaerts et al. (5) reported on the diffusion of BEL-1-producing isolates in various hospital centers of Belgium and also found that BEL-1 could be associated with other relevant β-lactamases, such as the VIM-1 metallo-β-lactamase (5).P. aeruginosa isolate 531 (this study) was recovered from a urine sample of a patient hospitalized in Roeselare, Belgium, in February 2007 for pneumonia and was resistant to all β-lactams but imipenem (Table ​(Table1).1). A synergy between aztreonam or ceftazidime and clavulanic acid-containing disks suggested the synthesis of an ESBL (19). PCR followed by sequencing using ESBL gene-specific primers (24) identified a novel gene encoding BEL-2, which differs from BEL-1 by a single amino acid substitution (Leu to Phe at Ambler position 162) (3). Transfer of a ß-lactam resistance marker from P. aeruginosa 531 to Escherichia coli or to P. aeruginosa reference strains was unsuccessful by either conjugation or transformation (25). Plasmid extraction performed as described previously (14) did not identify any plasmid, suggesting a chromosomal location of the bla_BEL-2-like gene in P. aeruginosa 531. A pulsed-field gel electrophoresis (PFGE) analysis (4) showed that isolates 531 (BEL-2 positive) and 51170 (BEL-1 positive), recovered from the same geographical area, were clonally related. A PCR mapping approach confirmed the presence of a class 1 integron whose structure was identical to that of In120 of P. aeruginosa 51170 (24) and identified an identical structure in P. aeruginosa 531 (data not shown). Overall, these data suggest that the bla_BEL-2 sequence likely resulted from a mutational event that had occurred in In120-carrying P. aeruginosa strains.

TABLE 1.

MICs of β-lactams^a