Identification of the THL binding site on human pancreatic lipase

Pancreatic lipase is considered as a serine hydrolase that plays a key function in dietary fat absorption by hydrolysing triglycerides into diglycerides and subsequently into monoglycerides and free fatty acids. Although it has been assumed [1,2] that porcine pancreatic lipase has two functionally important sites: a catalytic site involving Serj109, and a topographically distinct interfacial "recognition site" or " substrate binding site" controlled by Serı52, the catalytic mechanism has not been demonstrated experimentally thus far. On the other hand, the X-ray structure of human pancreatic lipase [3] shows clearly that Serj52 forms a triad with His263 and Asp 176 which givesa spatial superposition with the catalytic triad of the serine protease trypsin (Fig.1). \ 1102 esp Recently Tetrahyrolipstatin exe (THL), a_ selective and irreversible inhibitor of er pancreatic lipase has been used to identify the THL binding site on porcine pancreatic lipase. The result showed that THL binds to Serı52 of the lipase covalently [4]. The same attempt was also made for human pancreatic lipase, the data indicate strongly that ee human and porcine pancreatic see lipases share high : similarity/identity not only in their primary structure and enzymatic characteristics, but also in their catalytic mechanism

Flexprint substrate enzyme sensor for determination of daily glucose-profiles for diabetic patients

The goal is to develop a miniaturized system allowing continuous measurement of glucose concentration profiles over 24 hours for several days. The unique feature of the PharmaSens / IMT approach lies in the insertion mechanism and the needle size to assure optimum user-friendliness and patient comfort. The measurement method is based on classical amperometric detection using an enzymatic membrane. The sensor substrate is made on a flexprint substrate and consists of a 3-electrode cell on a needle-shaped tip of ~100 μm width and is covered with polymeric membranes. The sensor is integrated in a device that combines the insertion mechanism and electronics

Multicenter, Randomized Study of the Efficacy and Safety of Intravenous Iclaprim in Complicated Skin and Skin Structure Infections▿

Iclaprim is a novel antibacterial agent that is currently in development for the treatment of complicated skin and skin structure infections (cSSSI). Iclaprim specifically and selectively inhibits bacterial dihydrofolate reductase, a critical enzyme in the bacterial folate pathway, and exhibits an extended spectrum of activity against various resistant pathogens, including methicillin (meticillin)-resistant Staphylococcus aureus (MRSA). The objective of this randomized, double-blind phase II study was to compare the efficacy and safety of iclaprim to those of vancomycin in patients with cSSSI. Patients were randomized to receive 0.8 mg iclaprim/kg of body weight, 1.6 mg/kg iclaprim, or 1 g vancomycin twice a day for 10 days. Clinical cure rates for the 0.8- and 1.6-mg/kg-iclaprim treatment groups were comparable to that for the vancomycin treatment group (26/28 patients [92.9%], 28/31 patients [90.3%], and 26/28 patients [92.9%], respectively). Iclaprim also showed high microbiological eradication rates. Iclaprim exhibited an eradication rate of 80% and 72% versus 59% observed with vancomycin for S. aureus, the pathogen most frequently isolated at baseline. Five MRSA cases were observed, four in the 0.8-mg/kg-iclaprim arm and one in the vancomycin arm, and all were both clinically and microbiologically cured. Iclaprim exhibited a safety profile similar to that of vancomycin, an established drug for the treatment of cSSSI. Results from this study indicate that iclaprim is a promising new therapy for the treatment of cSSSI, in particular those caused by S. aureus, including MRSA