Exocrine pancreatic ductograms in insulin-dependent diabetes mellitus

OBJECTIVES: To examine the prevalence of abnormal pancreatic ductograms in patients with insulin-dependent diabetes mellitus (IDDM) and to determine the clinical characteristics of those patients. METHODS: Pancreatic exocrine morphology was studied by endoscopic retrograde pancreatography (ERP) in 43 patients with IDDM, 12 patients with islet cell antibody (ICA)-positive non-insulin-dependent diabetes mellitus (NIDDM), and 22 patients with ICA-negative NIDDM. RESULTS: ERP revealed a significantly higher prevalence of abnormal pancreatic ducts (dilation and stenosis, tortuosity, obstruction, and intraductal calculi) in the patients with IDDM (17/43, 40%) than in the patients with ICA-negative NIDDM (2/22, 9%, p = 0.018). IDDM patients who slowly progressed to insulin dependency more than 13 months after the onset of diabetes had a higher frequency of abnormal pancreatic ducts (13/22, 59%) than those who needed insulin therapy within 12 months after the onset (4/21, 19%, p = 0.016). There was no difference in duration of diabetes between the two groups. ICA-positive NIDDM patients also had a higher frequency of abnormal pancreatic ducts (7/12, 58%) than ICA-negative NIDDM patients (2/22, 9%, p = 0.0074). CONCLUSIONS: These results indicate that a high proportion of IDDM patients who have prolonged histories of non-insulin dependency with ICA suffer pancreatic exocrine impairment. A similarity between IDDM with a slowly progressive clinical course and fibrocalculous pancreatic diabetes seen in tropical countries also was suggested.     

Tenidap inhibits 5-lipoxygenase product formation in vitro, but this activity is not observed in three animal models

OBJECTIVE AND DESIGN: The effect of tenidap on the metabolism of arachidonic acid via the 5-lipoxygenase (5-LO) pathway was investigated in vitro and in vivo. MATERIALS AND TREATMENT: In vitro (cells). Arachidonic acid (AA) stimulated rat basophilic leukemia, (RBL) cells; A23817 activated neutrophils (human rat, and rabbit), macrophages (rat), and blood (human). In vitro (enzyme activity). RBL-cell homogenate; purified human recombinant 5-LO. In vivo: Rat (Sprague-Dawley) models in which peritoneal leukotriene products were measured after challenge with zymosan (3 animals per group), A23187 (11 animals per group), and immune complexes (3-5 animals per group), respectively. METHODS: 5-Hydroxyeicosatetraenoic acid (5-HETE) and dihydroxyeicosatetraenoic acids (diHETEs, including LTB4) were measured as radiolabeled products (derived from [14C]-AA) or by absorbance at 235 or 280 nm, respectively, after separation by HPLC. Radiolabeled 5-HPETE was measured by a radio-TLC analyser after separation by thin layer chromatography (TLC). Deacylation of membrane bound [14C]-AA was determined by measuring radiolabel released into the extracellular medium. 5-LO translocation from cytosol to membrane was assessed by western analysis. Rat peritoneal fluid was assayed for PGE, 6-keto-PGF1 alpha, LTE4 or LTB4 content by EIA and for TXB2 by RIA. RESULTS: Tenidap suppressed 5-LO mediated product production in cultured rat basophilic leukemia (RBL-1) cells from exogenously supplied AA, and in human and rat neutrophils, and rat peritoneal macrophages stimulated with A23187 (IC50, 5-15 microM). In addition, tenidap was less potent in inhibiting the release of radiolabeled AA from RBL-1 cells (IC50, 180 microM), suggesting that the decrease in 5-LO derived products could not be explained by an effect on cellular mobilization of AA (i.e., phospholipase). Tenidap blocked 5-hydroxyeicosatetraenoic acid (5-HETE) production by dissociated RBL-1 cell preparations (IC50, 7 microM), as well as by a 100000 x g supernatant of 5-LO/hydroperoxidase activity, suggesting a direct effect on the 5-LO enzyme itself. In addition, tenidap impaired 5-LO translocation from cytosol to its membrane-bound docking protein (FLAP) which occurs when human neutrophils are stimulated with calcium ionophore, indicating a second mechanism for inhibiting the 5-LO pathway. Surprisingly, tenidap did not block the binding of radiolabeled MK-0591, an indole ligand of FLAP, to neutrophil membranes. Although its ability to inhibit the cyclooxygenase pathway was readily observed in whole blood and in vivo, tenidap's 5-LO blockade could not be demonstrated by ionophore stimulated human blood, nor after oral dosing in rat models in which peritoneal leukotriene products were measured after challenge with three different stimuli. The presence of extracellular proteins greatly reduced the potency of tenidap as a 5-LO inhibitor in vitro, suggesting that protein binding is responsible for loss of activity in animal models. CONCLUSIONS: Tenidap inhibits 5-lipoxygenase activity in vitro both directly and indirectly by interfering with its translocation from cytosol to the membrane compartment in neutrophils. A potential mechanism for the latter effect is discussed with reference to tenidap's ability to lower intracellular pH. Tenidap did not inhibit 5-LO pathway activity in three animal models.     

Pharmacological properties of YM461, a new orally active platelet-activating factor antagonist

The antagonistic effect of YM461 [1-(3-phenylpropyl)-4-[2-(3-pyridyl)thiazolidin-4-ylcarbonyl]piperazine fumarate] against platelet-activating factor (PAF) was examined in severalin vitro andin vivo systems. We found that YM461 inhibited [³H]PAF binding to rabbit platelet membranes with a pK_i value of 8.90. YM461 inhibited PAF induced rabbit and human platelet aggregation with pA₂ values of 7.52 and 7.29, respectively; the slopes of the Schild plots were 1.07 and 1.01, respectively. However, YM461 at 10⁻⁴M did not affect rabbit and human platelet aggregation induced by ADP, collagen, arachidonic acid or epinephrine. YM461 inhibited PAF induced death in mice with an ED₅₀ (50% effective dose) value of 0.35 mg/kgp.o. YM461 at doses above 0.3 mg/kgi.v. inhibited PAF induced hypotension in rats. YM461 showed a dose-dependent inhibition of PAF induced hemoconcentration in rats with ED₅₀ values of 0.15 and 0.21 mg/kgp.o., respectively, at 0.5 and 1 hr after oral administration. The anti-PAF effect of YM461 persisted more than 6 hr after 3 mg/kgp.o. in rats. YM461 inhibited the bronchoconstriction induced by PAF with an ED₅₀ value of 1.2 mg/kgp.o. in anesthetized guinea pigs. Furthermore, the compound at doses above 3 mg/kgp.o. significantly inhibited antigen-induced anaphylactic asthma in conscious guinea pigs pretreated with mepyramine and propranolol. These results indicate that YM461 is a selective, potent and orally active PAF antagonist. Based on a paper presented at the Third International Conference on Platelet-Activating Factor and Structurally Related Alkyl Ether Lipids, Tokyo, Japan, May 1989.     

Measurement of pH in the vicinity of a cathode during the chloride electrowinning of nickel

An antimony microelectrode was prepared by quenching a molten Sb-Sb₂O₃ mixture (2 pct Sb₂O₃). The local pH in the vicinity of a nickel-plated copper cathode was directly measured using the microelectrode during the chloride electrowinning of nickel for a MCLE (matte chlorine leach electrowinning) process, where nickel metal is electrodeposited with a high current efficiency, 94 to 97 pct, from low-pH baths. The local pH at 328 K was increased by proton consumption during the electrolysis of aqueous electrolytes containing NiCl₂ (1.20 mol dm⁻³) and NaCl (0.43 mol dm⁻³) with the same concentrations as employed for the MCLE process. The difference in pH between the cathode surface and bulk solution increased with increasing cathodic current density. Nickel deposits with a metallic luster were obtained when the difference was not more than 1.2 pH units. The current efficiency was a maximum for electrolysis with a current density of 265 A m⁻² and bulk pH of 1.0 to 1.5; these optimal conditions coincided with those reported for the MCLE process: temperature 328 to 333 K, bulk pH 1.1 to 1.5, and current density 230 to 260 A m⁻². Electrolytes with lower NiCl₂ and NaCl concentrations resulted in a drop in current efficiency.     

SF/sub 6/ reclaimer from SF/sub 6//N/sub 2/ mixtures by gas separation with molecular sieving effect

This paper discusses the various methods for sulfur hexafluoride (SF/sub 6/) separation from a mixture of low concentrations of SF/sub 6/ in N/sub 2/ pressure swing adsorption (PSA) with a suitable kind of synthetic zeolite, which has the expected molecular sieving effect. This molecular sieving effect, derived from molecular size difference between SF/sub 6/ and N/sub 2/, is confirmed by the difference between two equivalent volumes filled with SF/sub 6/ and N/sub 2/. Prototype equipment of SF/sub 6/ separation and liquefaction, that is about 1 m cube in size and 150 kg in weight, has been assembled and tested. The ability of gas mixture handling is 13 l/min on average, and the SF/sub 6/ content is reduced to 0.0% (undetectable level) in separated N/sub 2/ to exhaust into the atmosphere.     

Investigation of loading rate and plate thickness effects on dynamic fracture toughness of PMMA

To investigate the effects of loading rate and plate thickness on the fracture toughness of PMMA (polymethyl methacrylate) under impact loading, two methods, A method and B method, are applied as follows. In the A method, a dynamic finite element method and a strain gage method are applied to measure the dynamic fracture toughness in the fracture test using an air gun. In the B method, a single axis strain gage method is applied to measure the critical dynamic stress intensity factor, namely dynamic fracture toughness, in the fracture test using a weight dropping type apparatus. The dimensions of the PMMA specimen are L = 140 mm length and W = 30 mm width. Three values of the plate thickness B, 15.0 mm, 10.0 mm and 5.0 mm, are selected to investigate the plate thickness effect in the fracture test. Both results by the A and B methods precisely indicated the minimum value and the loading rate effect on the dynamic fracture toughness.     

Size dependence of the characteristics of Si single-electrontransistors on SIMOX substrates

A Si single-electron transistor (SET) was fabricated by converting a one-dimensional (1-D) Si wire on a SIMOX substrate into a small Si island with a tunneling barrier at each end by means of pattern-dependent oxidation. Since the size of the Si island became as small as around 10 nm owing to this novel technique, the total capacitance of the SET was reduced to a value of the order of 1 aF, which guaranteed the conductance oscillation of the SET even at room temperature. Furthermore, a linear relation between the designed wire length and the gate capacitance of SET's was obtained, which clearly indicates that the single island was actually formed in the middle of the one dimensional Si wire. These results were achieved owing to the highly reproducible fabrication process based on pattern dependent oxidation of SIMOX-Si layers     

Multifilament niobium-tin conductors

A new Nb3Sn wire fabrication method has been developed, improving wire drawing workability and superconducting properties, such as stability and ac losses. A cross section of the single filament wire consists of a niobium tube with a copper sheathed tin rod inside and high conductivity copper tube outside. These constituents show scarcely any workhardening. Wires with 54 to 295 filaments were drawn down to 0.2 mm to 1.0 mm diameter. Heat-treatment conditions to obtain the highest critical current were clarified as a function of the tin content inside the niobium tube. The effect of bend strain in Nb3Sn on the critical current was also examined for samples with different wire diameters and Nb3Sn layer thickness. Losses were measured for twisted and non-twisted samples by means of magnetization experiments. Results were compared with calculated values. It was found that the effective resistivity between Nb3Sn filaments was one order of magnitude higher than that of pure copper. A coil was constructed using a 1 km long Nb3Sn composite having 258 filaments with 1 × 2 mm cross section. The maximum field obtained was 10.65T at 236A in the 6T backing field by NbTi solenoid.     

Hydrogen embrittlement susceptibility of microstructures formed in multipass weld metal for HT780 class steel

The effect of reheating by following passes on the hydrogen embrittlement of MAG weld metal for HT780 class steels has been investigated by using specimens subjected to simulated thermal cycles. The hydrogen-charged specimens exhibited transgranular quasi-cleavage fracture and intergranular fracture along prior austenite grain boundaries on slow strain rate tensile (SSRT) tests, depending on the reheated temperature and charged hydrogen content. The reduction in elongation of hydrogen-charged specimens became more significant when intergranular fracture occurred. When specimens in as-welded state and precedently reheated at coarse grained HAZ temperature of 1,623 K were reheated at a tempering temperature of 873 K, significant amount of intergranular fracture occurred at charged hydrogen contents above 3 ppm in spite of the decrease in hardness. The specimen reheated at 1,173 K showed no intergranular fracture even after receiving the reheating at 873 K at a hydrogen content of 6 ppm, suggesting the strong influence of the prior austenite grain size on the hydrogen-induced intergranular embrittlement. The measurement of hydrogen content desorbed from the hydrogen-charged specimen at room temperature suggested that the intergranular fracture caused by the reheating at 873 K was associated with an increase in susceptibility to hydrogen embrittlement of the prior austenite grain boundary itself rather than a decrease in the amounts of trapping sites such as dislocation and retained austenite.