Our study indicates the constant effect of SG in the acceleration of gastric emptying of solids, which occurs faster, not only in short but also in long-term postoperatively. Such effects on gastric motility, in combination with the reported alterations in gut hormones, may explain how this 'food limiting' operation results in weight loss.

Human glutamate dehydrogenase (GDH), an enzyme central to the metabolism of glutamate, is known to exist in housekeeping and nerve tissue-specific isoforms encoded by the GLUD1 and GLUD2 genes, respectively. As there is evidence that GDH function in vivo is regulated, and that regulatory mutations of human GDH are associated with metabolic abnormalities, we sought here to characterize further the functional properties of the two human isoenzymes. Each was obtained in recombinant form by expressing the corresponding cDNAs in Sf9 cells and studied with respect to its regulation by endogenous allosteric effectors, such as purine nucleotides and branched chain amino acids. Results showed that L-leucine, at 1.0 mM, enhanced the activity of the nerve tissue-specific (GLUD2-derived) enzyme by ϳ1,600% and that of the GLUD1-derived GDH by ϳ75%. Concentrations of L-leucine similar to those present in human tissues (ϳ0.1 mM) had little effect on either isoenzyme. However, the presence of ADP (10 -50 M) sensitized the two isoenzymes to L-leucine, permitting substantial enzyme activation at physiologically relevant concentrations of this amino acid. Nonactivated GLUD1 GDH was markedly inhibited by GTP (IC 50 ϭ 0.20 M), whereas nonactivated GLUD2 GDH was totally insensitive to this compound (IC 50 Ͼ 5,000 M). In contrast, GLUD2 GDH activated by ADP and/or L-leucine was amenable to this inhibition, although at substantially higher GTP concentrations than the GLUD1 enzyme. ADP and L-leucine, acting synergistically, modified the cooperativity curves of the two isoenzymes. Kinetic studies revealed significant differences in the K m values obtained for ␣-ketoglutarate and glutamate for the GLUD1-and the GLUD2-derived GDH, with the allosteric activators differentially altering these values. Hence, the activity of the two human GDH is regulated by distinct allosteric mechanisms, and these findings may have implications for the biologic functions of these isoenzymes.

The co-expression of KIT receptor and its ligand stem cell factor (SCF) has been reported in biopsy specimens of Merkel cell carcinoma (MCC). However, the functional role of SCF/KIT in the pathogenesis of this aggressive tumor has not been elucidated. The present study reports expression and effects of SCF and KIT in the Merkel cell carcinoma cell line MCC-1 in vitro. SCF and KIT were endogenously co-expressed in MCC-1 cells. Exogenous soluble SCF modulated KIT receptor mRNA and protein expression, stimulated growth of MCC-1 cells, upregulated endogenous activation of KIT, AKT, and of extracellular signal-regulated kinase (ERK) 1/2 signaling pathway. On the contrary, an inhibitory antibody that neutralized the KIT ligand binding site, reduced growth of MCC-1 cells, as did high doses of the KIT kinase inhibitors imatinib and nilotinib. Also, inhibitors of KIT downstream effectors, U0126 that blocks MEK1/2 as well as wortmannin and LY294002 that inhibit phosphatidylinositol 3-kinase-dependent AKT phosphorylation, inhibited the proliferation of MCC-1 cells. These data support the hypothesis that KIT is activatable by paracrine or autocrine tumor cell-derived SCF and stimulates growth of Merkel cell carcinoma in vitro. Blockade of KIT and the downstream signaling cascade at various levels results in inhibition of Merkel cell carcinoma growth in vitro, suggesting targets for therapy of this cancer.

Shockwave lithotripsy is a safe and efficient treatment modality for ureteral stones in pediatric patients. In expert hands, ureteroscopy can be successfully applied in case of SWL failure.

Rhabdomyolysis is a rare complication of serious surgical procedures, and constitutes a clinical and biochemical syndrome, caused by injury and destruction of skeletal muscles. It is accompanied by pain in the region of the referred muscle group, increase in creatine phosphokinase levels, myoglobinuria, often with severe renal failure, and finally multi-organ system failure and death, if not treated in time. The main risk factor in the development of postoperative rhabdomyolysis is prolonged intraoperative immobilization of the patient. Morbidly obese patients who undergo laparoscopic bariatric operations should be considered high-risk for rhabdomyolysis, from extended immobilization and pressure phenomena in the lumbar region and gluteal muscles. We report a 20-year-old woman with BMI 51, who underwent a prolonged laparoscopic Roux-en-Y gastric bypass. Postoperatively, she presented severe myalgia in the gluteal muscles and lumbar region, oliguria and creatine phosphokinase levels that reached 38,700 U/L. She was treated with intensive hydration and analgesics, and did not develop acute renal failure because diagnosis and treatment were attained immediately.