The role of the protein glycosylation state in the control of cellular transport of the amyloid beta precursor protein

The amyloid beta precursor protein can exist as both a membrane-bound and a secreted protein, with the former having the potential to generate the amyloid beta peptide present in the neuritic plaques which are characteristic of Alzheimer's disease. In this study, we have used a clone of the AtT20 mouse pituitary cell line which expresses high levels of the amyloid beta precursor protein to characterize the glycosylation state of the secreted and membrane-bound forms of the protein and to examine the role of post-translational modifications in protein processing. Lectin blot analysis of immunoprecipitated amyloid beta precursor protein demonstrated that the soluble form of the protein contains significant amounts of sialic acid, with the lectin staining being reduced in the particulate cellular fractions. Treatment of the cells with mannosidase inhibitors to interfere with the formation of complex-type N-linked glycans resulted in a decrease in secreted amyloid beta precursor protein and an increase in the level of the cellular form of the protein. The increase in amyloid beta precursor protein levels in the cellular fraction was accompanied by an increase in perinuclear staining. Furthermore, cells overexpressing the alpha2,6(N)-sialyltransferase enzyme also demonstrated an increase in amyloid beta precursor protein secretion. These results suggest that the presence of terminal sialic acid residues on complex-type N-glycans may be required for the optimal transport of the amyloid beta precursor protein from the Golgi to the cell membrane with the subsequent cleavage to generate the secreted form of the protein.     

Insulin infusion protocol for critical care units.

PURPOSE: An insulin infusion protocol for critical care units is described. SUMMARY: Evidence that aggressive glycemic control improves outcomes led physicians, nurses, dietitians, and pharmacists at a trauma center to develop an insulin infusion protocol. Before the protocol, elevated blood glucose concentrations were often not treated until they reached 200 mg/dL or higher. Insulin infusions were underutilized and were often not started until capillary blood glucose concentrations were greater than 350 mg/dL for 12 or more hours. When orders for an insulin infusion were written, they did not include directions for dosage adjustment, and the goal blood glucose range varied. A preliminary protocol was drafted allowing adjustments in insulin administration to be based on changes in capillary blood glucose values since the previous blood glucose measurement. The protocol was presented to a multidisciplinary team and further refined. The targeted blood glucose concentration range was 80-130 mg/dL. After the targeted range was achieved for a patient, if the blood glucose level continued to decrease over three consecutive measurements, the infusion rate was decreased by 0.5 or 1 unit/hr, depending on the capillary blood glucose level. Data for the first 30 patients were collected from September 2003 to August 2004. It took 2-36 hours (mean, 12.6 hours) to bring the capillary blood glucose concentration to less than 130 mg/dL. Among 2,845 capillary blood glucose measurements, there were 15 cases of hypoglycemia (0.4%) requiring treatment with 50% dextrose injection. CONCLUSION: A multidisciplinary effort resulted in the development of an insulin infusion protocol for use in critical care units.     

Acute upper gastrointestinal bleeding in patients on long-term oral anticoagulation therapy： Endoscopic findings, clinical management and outcome

AIM: Acute gastrointestinal bleeding is a severe complication in patients receiving long-term oral anticoagulant therapy. The purpose of this study was to describe the causes and clinical outcome of these patients. METHODS: From January 1999 to October 2003, 111 patients with acute upper gastrointestinal bleeding (AUGIB) were hospitalized while on oral anticoagulants. The causes and clinical outcome of these patients were compared with those of 604 patients hospitalized during 2000-2001 with AUGIB who were not taking warfarin. RESULTS: The most common cause of bleeding was peptic ulcer in 51 patients (45%) receiving anticoagulants compared to 359/604 (59.4%) patients not receiving warfarin (P<0.05). No identifiable source of bleeding could be found in 33 patients (29.7%) compared to 31/604 (5.1%) patients not receiving anticoagulants (P=0.0001). The majority of patients with concurrent use of non-steroidal anti-inflammatory drugs (NSAIDs) (26/35, 74.3%) had a peptic ulcer as a cause of bleeding while 32/76 (40.8%) patients not taking a great dose of NSAIDs had a negative upper and lower gastrointestinal endoscopy. Endoscopic hemostasis was applied and no complication was reported. Six patients (5.4%) were operated due to continuing or recurrent hemorrhage, compared to 23/604 (3.8%) patients not receiving anticoagulants. Four patients died, the overall mortality was 3.6% in patients with AUGIB due to anticoagulants, which was not different from that in patients not receiving anticoagulant therapy. CONCLUSION: Patients with AUGIB while on long-term anticoagulant therapy had a clinical outcome, which is not different from that of patients not taking anticoagulants. Early endoscopy is important for the management of these patients and endoscopic hemostasis can be safely applied.     

Characterization of herpes simplex virus type 1 recombinants that express and incorporate high levels of HCV E2-gC chimeric proteins

We report the construction of two HSV-1 recombinants encoding chimeric forms of the E2 glycoprotein of HCV-1a composed of the ectodomain of E2 (aa384-611 or 384-711) fused to different parts of the transmembrane and cytoplasmic domain of the HSV-1 gC glycoprotein (gC). The parental HSV-1, known as KgBpK(-)gC(-), is deleted for gC and the main heparan sulphate (HS) binding domain of gB, and it exhibits impaired binding (ca. 80%) to HS compared to the wild type virus KOS [Laquerre, S., Argnani, R., Anderson, D.B., Zucchini, S., Manservigi, R., Glorioso, J.C., 1998. Heparan sulphate proteoglycan binding by herpes simplex virus type 1 glycoproteins B and C, which differ in their contributions to virus attachment, penetration, and cell-to-cell spread. J. Virol. 72, 6119-6130]. We show that gC:E2 proteins are efficiently expressed and transported to the cell surface. We also demonstrate that HSV-1 can incorporate both gC:E2 chimeric proteins into particles and show that incorporation of both chimeric molecules in the viral envelope partially restored binding (ca. 20%) of the HSV-1 recombinants to heparan sulphate. Finally, we showed that the gC:E2ScaI chimeric glycoprotein was able to bind a recombinant form of hCD81 and virion-expressed gC:E2ScaI permitted the binding of the HSV-1 recombinant virus to the hCD81 molecule.     

Drainage tube endoscopy: a contribution to the management of severe acute pancreatitis?

Peritoneal lavage is one of the interventional approaches that have gained some attention in the early, toxaemic phase of acute pancreatitis. Additionally some kind of drainage is necessary for suppurative collections that characterize the late phase of the disease. In both the above situations tube plugging is a common problem and it is usually associated with a relapse of the patient's septic state and newly formed collection(s) on abdominal CT. Two cases are presented, in early and in late phases respectively, in which drainage tube adoscopy (DTE) re-established tube patency and ensured drainage. DTE may represent an alternative to surgery or to CT-guided paracentesis and evacuation of newly formed intra-abdominal collections secondary to tube obstruction. Received: 24 March 1997 Accepted: 7 August 1997     

The presence of insomnia and depression contributes to the acceptance of an initial treatment trial of continuous positive airway pressure therapy in patients with obstructive sleep apnea

Sleep and Breathing - The presence of comorbid insomnia and sleep apnea (COMISA) reduces the initial acceptance of continuous positive airway pressure (CPAP) therapy in 39–58% of patients...     

The effect of preemptive use of pregabalin on postoperative morphine consumption and analgesia levels after laparoscopic colorectal surgery: a controlled randomized trial

International Journal of Colorectal Disease - In order to reduce postoperative opioid administration and pain levels in patients submitted to laparoscopic colectomy, we assessed the efficacy of...     

Dye penetration in dry and water-filled gaps along root fillings

AIM: The aim of this study was to investigate the influence of hydration in voids along root fillings on methylene blue penetration. METHODOLOGY: A total of 80 human root canals were prepared using a step-back technique and filled with a zinc oxide based sealer and gutta-percha. Leakage along the fillings was measured by a transport fluid model and classified into three categories: gross leakage (GL), slight leakage (SL) and no leakage (NL). Specimens with NL and SL were immersed into methylene blue (MB) 2% for 24 h (group I). Specimens with GL which had wide gaps filled with water were randomly divided into two groups (II, III). Transport air was applied to remove water from gaps only in specimens of group III. All tested specimens from groups II and III were also immersed into MB 2% for 24 h. Each specimen was then split longitudinally and linear measurements of dye penetration were recorded. RESULTS: Group III (with dry gaps) showed significantly more dye penetration than group II. No significant difference was found between group I and group II. CONCLUSIONS: Methylene blue penetrates along root fillings more easily in dry gaps than in water-filled gaps.