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 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The prevalence of marginal zinc nutriture in several populations of people in this country and the lack of reports on the effect of marginal zinc nutriture in experimental animals prompted us to look at pancreatic acinar cell function and morphology in rats fed a zinc-deficient diet ad libitum: 4 and 50 ppm zinc-supplemented diets in amounts isocaloric to a zinc-deficient diet and Rodent-Blox fed ad libitum for a period of 49 +/- 1 (SEM) days. Because of a diminished rate of energy expenditure in zinc-deficient rats, animals receiving 50 ppm zinc-supplemented diets were offered less food, resulting in decreased body weight and pancreas weight, DNA, RNA, total protein, lipase, amylase, and secretion of protein. Specific changes due to zinc deficiency included (a) further decrease in body weight and (b) increase in content, specific activity, and secretion of lipase. Both the size and volume fraction of zymogen granules were reduced in zinc deficiency. The lumina of acinar and small ducts were collapsed with paucity of secretion products. Zinc deficiency may therefore lead to a defect in discharge mechanism. A further reduction in volume fraction of zymogen granules in the 4 ppm zinc-supplemented group was associated with increased secretion of serine proteases (trypsinogen and chymotrypsinogen), which constitute approximately 46% of total secretory protein in the pancreas under normal dietary conditions. This indicated an accelerated discharge due to an unknown mechanism. Changes in the secretion of digestive enzymes in the present study simulated ethanol-induced secretory alterations that were previously observed. Because abnormal zinc nutriture and chronic alcoholism are commonly associated, it is speculated that zinc deficiency may play a role in the ethanol-induced secretory alterations.
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PMID:Pancreatic acinar cell function and morphology in rats fed zinc-deficient and marginal zinc-deficient diets. 241

The present study was done to determine interaction of ethanol and marginal zinc nutriture on morphology and function of rat pancreas. Sprague-Dawley rats were maintained on Wayne Rodent-Blox ad libitum; marginal zinc-deficient diet plus ethanol ad libitum and pair fed with animals fed marginal zinc-deficient liquid diet and zinc-supplemented liquid diet with ethanol for 33 (+/- 1 SEM) days. Body, pancreas, liver, heart, and kidney weights were determined, and studies of pancreatic DNA, RNA, total proteins and newly labeled proteins, amylase, lipase, trypsinogen, and chymotrypsinogen were done on pancreatic lobules in vitro. Ethanol feeding independent of the zinc content of the diet caused a decrease in zinc content of the liver, body weight, liver and pancreas weight, pancreatic DNA, total protein, and amylase concentration and an increase in lipase and trypsinogen concentrations and in secretion of amylase and lipase. Interaction of the marginal zinc diet and ethanol feeding resulted in a decreased synthesis of RNA and secretion of newly synthesized protein and an increase in secretion of serine proteases. Morphological studies revealed a reduction in the number of zymogen granules in animals fed low levels of zinc, also with an accumulation of lipid droplets when the diet contained ethanol. These studies confirmed our previous observations of specific injury to the pancreas due to marginal zinc nutriture or to ethanol, independent of each other. Marginal zinc nutriture in concert with ethanol resulted in impaired RNA synthesis and secretion of nascent proteins and increased secretion of serine proteases. These data indicate that altered zinc metabolism induced by ethanol per se may contribute to ethanol-induced disturbance of pancreatic function.
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PMID:Interaction between marginal zinc deficiency and chronic alcoholism: pancreatic structure and function in rats in vitro. 243 69

Trypsinogen activation peptide (TAP) concentration and alpha 2-macroglobulin-trypsin complex (alpha 2M-T) activity were measured in two experimental models of acute pancreatitis in rats to evaluate the significance of activation of trypsinogen in acute pancreatitis. TAP concentration and alpha 2M-T activity in serum rose significantly in trypsin-taurocholate-induced hemorrhagic acute pancreatitis, while in cerulein-induced edematous acute pancreatitis they did not rise in spite of a similar increase in immunoreactive trypsin. When rats in trypsin-taurocholate-induced pancreatitis were treated by protease inhibitor (FUT-175; nafamostat mesilate; FUT group), alpha 2M-T activity in serum was significantly lower than that in nontreated controls (mean +/- SEM, 20.8 +/- 1.43 U/L in the FUT group vs 79.1 +/- 24.5 in controls; p < 0.01). The survival rate at 24 h was significantly improved in the FUT group compared with the controls (70 vs 43%; p < 0.05). The increase in TAP concentration in the FUT group was similar to that in controls. The TAP concentration in pancreatic tissue at 24 h was significantly (p < 0.01) lower in the survival group (7.8 +/- 0.8 ng/ml) than in the lethal group (25.9 +/- 3.7 ng/ml). Activation of trypsinogen and its subsequent enzyme activity play an important role in the evolution of severe acute pancreatitis.
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PMID:Activation of trypsinogen in experimental models of acute pancreatitis in rats. 754 73

This work investigates the use of spray freeze-drying (SFD) to produce protein loaded particles suitable for epidermal delivery. In the first part of the study, the effects of formulation and process conditions on particle properties are examined. Aqueous solutions of trehalose produce SFD particles in the size range 20-80 microm, with a smooth, textured surface, but having high internal porosity. The latter was visualized using SEM and a novel particle embedding and sectioning technique. Use of an annealing step during the freeze-drying cycle caused the particles to shrink, reducing hereby porosity and also the measured rate of moisture uptake into these amorphous particles. SFD pure mannitol was approximately 40% amorphous, but not hygroscopic. Incorporation of dextran 37,500 into a combined amorphous trehalose/mannitol formulation led to increased particle shrinkage and lower particle porosity on annealing. The model protein trypsinogen lost approximately 15% activity during SFD of solutions containing 50 mg/mL protein, but was only marginally aggregated (1.4%). It is suggested that trypsinogen forms an irreversible partially unfolded state or molten globule on SFD/rehydration. The pure protein was also partially inactivated without aggregation during atomization into air. Surprisingly, neither activity loss nor aggregation were detected on atomization of the protein solution into liquid nitrogen. Quench-freezing of small droplets may reverse the partial unfolding of trypsinogen occurring on atomization into air. The origin of the trypsinogen inactivation during SFD must therefore be the subsequent freeze-drying step of this multistep process. Isolated freeze drying of trypsinogen produces strong aggregation and equivalent inactivation. This result suggests that trypsinogen behaves differently during freeze drying from frozen droplets and from bulk solution in a vial. In the former case the protein forms an irreversible partially unfolded state, whereas in the latter case aggregates are formed. Trypsinogen inactivation during SFD could be completely prevented by the presence of trehalose in the formulation. Electron Spectroscopy for Chemical Analysis (ESCA) showed a high surface excess of the protein in the SFD particles, which was reduced on inclusion of Polysorbate 80, but not trehalose. Taken together, these results help to elucidate the complex destabilization behavior of trypsinogen during SFD.
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PMID:Spray-freeze-drying for protein powder preparation: particle characterization and a case study with trypsinogen stability. 1222 40