RESUMEN

The metabolic effects of protein malnutrition on growth and development of the exocrine pancreas are largely unknown. The aim of the present study was to evaluate the effects of protein malnutrition on pancreatic protein and DNA synthesis during postnatal development. Rat dams and their offspring were fed a protein-deficient diet (6% casein) or a control diet (25% casein) during gestation, lactation and after weaning. Pancreatic protein and DNA synthesis were measured in vitro at postnatal ages 1, 3, 10, 23, 36 and 60 days, by assessing [3H]leucine and [3H]thymidine incorporation in freshly isolated acini. Different patterns of protein synthesis were seen in the two groups. At birth, pancreatic protein synthesis was low in both control and malnourished animals. At day 3, protein synthesis in the control acini increased 10-fold while synthesis in acini of the malnourished animal group was only 50% of age-matched control values. No differences in protein synthesis were detected between the control and malnourished groups between 10 and 36 days of age. At 60 days (adulthood), acinar protein synthesis declined in the control-fed rats, but a significant increase was observed in the malnourished animals (p < 0. 0005). At birth, DNA synthesis was high in the acini from both control and malnourished animals. The low-protein diet induced a slight reduction in DNA synthesis at day 3, without altering the general pattern during later stages of development. In conclusion, protein deprivation has variable effects on pancreatic protein and DNA synthesis at different stages of postnatal development. Furthermore, the mechanisms of control within acini appear to be intrinsically regulated.

Asunto(s)

RESUMEN

The diagnosis of cystic fibrosis (CF) is not always certain, despite extensive clinical evaluation, multiple sweat chloride tests, and genotype analysis. We hypothesized that nasal transepithelial potential difference measurements have a useful role in this situation. In 11 patients without an established diagnosis of CF, results of simultaneous nasal potential difference (PD) and sweat chloride measurements were compared with those from control subjects, obligate CF heterozygotes, and patients with a confirmed diagnosis of CF. Two patients conformed to the PD profile for CF patients, whereas nine had values corresponding to those of the healthy control subjects. Subsequently the 5-thymidine (IVS8-5T) CF gene variant was identified in the two patients with abnormal PD measurements.

Asunto(s)

RESUMEN

We investigated the development of the exocrine pancreas in Cftr-/- mice in comparison with age-matched littermates (Cftr+/+, Cftr+/-) up to 100 d postnatally. Controls were weaned either to mouse chow or a liquid diet; Cftr-/- mice were weaned solely to a liquid diet. Solid-fed control mice gained weight and showed a progressive increase in pancreatic protein, DNA, amylase, lipase, trypsin, and chymotrypsin activities. Liquid-fed control mice showed similar postnatal somatic and pancreatic growth, except that amylase and lipase activities were lower than in the solid-fed controls. Cftr-/- mice exhibited significantly lower body and pancreatic weights than did controls. Pancreatic protein content and enzyme activities (notably amylase and lipase) were consistently lower than in the age-matched litter-mates fed either diet. The reduction in lipase activity in Cftr-/- mice was noted before weaning. We concluded that the liquid diet influenced postnatal exocrine pancreatic development in mice. However, a further reduction in postnatal pancreatic growth and enzymatic activities in the Cftr-/- mice was noted. These alterations could be due to the primary cystic fibrosis defect, although secondary factors, such as malnutrition induced by decreased dietary intake or abnormal absorptive capacity, may be responsible.

Asunto(s)

Asunto(s)

RESUMEN

Polyvinyl alcohol (PVA)-coated polyethylene tubing, with or without immobilized heparin, caused severe thrombocytopenia and enhanced the production of new platelets when inserted in a chronic arteriovenous shunt in canines. A similar length of uncoated polyethylene tubing neither lead to thrombocytopenia nor significantly enhanced platelet regeneration, relative to the shunt only without a test section. Platelet regeneration was monitored by the malondialdehyde assay, which was assumed to make a distinction between "new" and "old" platelets. This distinction was combined with the platelet count values to enable calculation of the cumulative consumption curve and the initial fractional consumption rate in the presence of a non constant platelet count. The resulting initial fractional consumption rates were: 34%/day for PVA, 20.5%/day for polyethylene, and 18%/day for the shunt only blank.

Asunto(s)

RESUMEN

The patency of heparin-PVA coated 1.14 mm i.d. polyethylene tubes was greater than that of control tubes without heparin in a novel test section that enabled ex vivo evaluation in dogs at low flow and shear rates (2-10 ml/min). Low shear rates were achieved by diverting a small portion of a chronic A-V shunt flow through Y-connectors into the small diameter test tubing. For shear rates in the range of 200-650 s-1 half the heparin-PVA tubes remained patent for longer than 72 min whereas half the control tubes (PVA only) only remained patent for longer than 30 min. At higher shear rates (500-1000 s-1), the 50% patency times for heparin-PVA and PVA were 225 and 123 min respectively. The increased patency at the higher shear rates was attributed more to the effect of the connector than just shear rate. The higher shear rates were achieved by changing from a Y-connector in which the small diameter side-branch was cut flush to the larger diameter main line to one in which the small diameter test tubing protruded into the lumen of the main line; the latter 'protruding' connector was presumed to result in less platelet pre-activation than the other. This method has been found useful for assessing the thrombogenicity of heparinized tubes at low flow rates.

Asunto(s)

RESUMEN

A technique is described for an extracorporeal arteriovenous shunt in dogs which allows the testing of biomaterials in the shunt for several months in the same animal. The details of the preparation of the tubes and of the surgical technique are given. In contrast to other techniques, encircling ligatures are not placed around the cannulated blood vessels.

Asunto(s)

RESUMEN

The patency of heparin-polyvinyl alcohol (hep-PVA) coated polyethylene tubing was found to be significantly longer than control tubes coated with polyvinyl alcohol (PVA) but without heparin at low flow rates in dogs using a novel parallel flow arteriovenous shunt designed to avoid surgical artifacts. A standard Silastic chronic shunt (3.18 mm i.d.) was inserted between the iliac artery and vein of a dog. After a 2-week recovery period, a small diameter coated polyethylene tube (1.14 mm i.d.) was connected in parallel with the exteriorized portion of the chronic shunt through a pair of Silastic Y-connectors, so that less than 3% of the shunt flow was diverted into the test tube. The chronic shunt was reused many times over a greater than 6 month patency period, eliminating the need for frequent surgery and reducing interanimal variability in the results. The difference in patency between heparinized and control tubes was greater at higher mainshunt flow rates indicating the presence of a significant effect of the Y-connectors on platelet adhesion or aggregation. This effect was manifested in a time-dependent reduction in circulating platelet count. Scanning electron microscopy (SEM) examination of the midportion of the heparinized tubes after occlusion demonstrated the absence of platelet and fibrin deposits, unlike the control tubes without heparin. Although the Y-connectors played a significant role, they did not dominate the thrombotic processes occurring in this shunt and consequently the biological effectiveness of the immobilized heparin could be demonstrated.

Asunto(s)