Aging and exocrine pancreatic function.

In view of the limited information concerning the influence of aging on exocrine pancreatic function, the authors undertook the present study. To examine a large number of elderly persons, including people of very advanced age (80 years and over), pancreatic function was studied by using the fluorescein dilaurate test (pancreolauryl test), one of the most recent tubeless, noninvasive pancreatic function tests. Sixty healthy noninstitutionalized elderly individuals (35 women and 25 men, aged 66 to 88 years, mean 78) participated in the study. Thirty-six healthy younger subjects (16 women and 20 men, aged 21 to 57 years, mean 36) were also studied as controls. All elderly subjects showed a strictly normal fluorescein dilaurate test. No significant differences in the pancreatic function test results were observed between the elderly under 80 years old and those over 80 years old. The authors conclude that the aging process per se does not significantly affect exocrine pancreatic function and, more particularly, does not impair the digestive capacity of the elderly person.

Spectral shift of fluorescein and carboxyfluorescein in the anterior chamber of the rabbit eye following systemic administration.

Systemically administered fluorescein is converted to fluorescein glucuronide. The conjugate is fluorescent and interferes with the measurement of fluorescein in the anterior chamber. Carboxyfluorescein is a hydrophilic derivative of fluorescein. In the rabbit, carboxyfluorescein is not converted as readily to a fluorescent metabolite. Thus, carboxyfluorescein has potential advantages as a quantitative fluorophore for studies of aqueous humor dynamics.

Carboxyfluorescein distribution in ocular tissues of normal and diabetic rats.

Quantitative fluorescence microscopy was used to study carboxyfluorescein distribution across the blood-ocular barrier of control and streptozotocin diabetic rats at 2 min, 1 and 2 hr after dye injection (125 mg/kg iv). Measurement of dye concentrations in plasma, urine and feces demonstrated increased plasma clearance and increased urinary clearance of carboxyfluorescein in diabetic rats. Unbound plasma dye concentration in the diabetic animals fell to 34% of the control level at 1 hr after injection; the corresponding plasma concentration vs. time integral was reduced to only 74% of the control value. The presence of a less fluorescent glucuronide conjugate of carboxyfluorescein was not detected in plasma, urine or feces. Fluorescence intensity in the ocular tissues measured, including choriocapillaris, pigment epithelium, retina, ciliary epithelium, iris, and cornea, was not higher for diabetic than for control rats. In addition, there was no indication of localized dye leakage into retina through defects in the pigment epithelial and vascular endothelial barriers or of increased dye entry at the optic disc, a site of blood-retinal barrier discontinuity. Normalization of tissue fluorescence intensity measurements at the different time intervals to compensate for disparity in concurrent plasma dye concentrations resulted in significantly higher levels in diabetic retinas at 1 hr. However, because this difference was not manifest when the plasma dye concentration vs. time integral was used to normalize the data, it is concluded that no greater accumulation of carboxyfluorescein occurs in the retina of diabetic rats over the time period studied.

Radioiodinated Rhodamine-123: a potential cationic hepatobiliary imaging agent.

The labelling of the cationic dye Rhodamine-123 with 125I is described. The biodistribution of the iodinated Rhodamine-123 has been determined at different time intervals after intravenous injection into fasted rats. It turned out that the dye is predominantly cleared by the liver and discharged into the bile. The bile acid taurocholate did not enhance the rate of excretion of 125I-Rhodamine-123.

Reproducibility of the fluorescein dilaurate pancreatic function test.

The indirect pancreatic function test, the fluorescein dilaurate test, was performed twice on nine healthy volunteers. The test is based on the renal excretion of fluorescein liberated from an ingested fluorescein ester by pancreatic enzymes. As a control, fluorescein sodium was ingested under similar conditions. The results of the test are expressed as the ratio of the amount of fluorescein excreted in the test part and the control part, forming the test/control (T/C) ratio. The mean values of excreted fluorescein correlated well with those reported by other authors. The coefficient of variation was 35% in the repeated test and of the same order in the series of individuals. The test cannot be recommended as a quantitative test until further investigation has been performed. Its use as a screening test is found questionable.

[Diagnosis of pancreatic insufficiency with fluorescein dilaurate in patients with cystic fibrosis (author's transl)]. / Diagnose der exokrinen Pankreasinsuffizienz mit Fluorescein-Dilaurat bei Patienten mit cystischer Fibrose.

The tubeless pancreas-function test with fluorescein dilaurate, which is based on the saponification of the test substance by pancreas-specific arylesterases, and which has proved itself in adults, was given to children for the first time. After reduction of the size of the test dose and the amount of liquid to be drunk, there were no difficulties in carrying out the test. Elimination of the fluorescein released from the flourescein dilaurate and excreted via the kidneys was clearly less in patients with cystic fibrosis than in normal subjects. Thus, the test in its modified form for children can provide adequate differentiation between normal and pathological pancreas function.

Study of fluorescein glucuronide. I. Isolation from urine.

A method for isolating fluorescein glucuronide from the urine using silica gel chromatography and preparative high-performance liquid chromatography is described. The product obtained was free from significant fluorescent impurity on thin-layer chromatography and analytical high-performance liquid chromatography.

Studies on the pharmacokinetics of fluorescein and its dilaurate ester under the conditions of the fluorescein dilaurate test.

Some aspects of the pharmacokinetics of fluorescein have been studied under the conditions of the fluorescein dilaurate test (Pancreolauryl-Test) in healthy volunteers. Dependence of fluorescein excretion on urine volume was investigated in a retrospective study in 370 patients. For intravenously administered fluorescein mean Cmax was 10.9 micrograms/ml with a mean elimination half-life of 286 min. For orally administered fluorescein sodium mean Cmax was 3.5 micrograms/ml with a tmax of 120 min and a t 1/2 of 267 min. Bioavailability of fluorescein by oral administration was 99%. By contrast, fluorescein from fluorescein dilaurate showed a 56% bioavailability under the conditions of the test with a Cmax of 1.8 micrograms/ml, a tmax of 270 min and a tt 1/2 of 246 min. Following enteral absorption of fluorescein hepatic extraction and enterohepatic circulation via the bile occurs, but although the concentrations of fluorescein in the bile may exceed those in the urine the absolute amount is likely to be small. In spite of the enterohepatic circulation fluorescein cleared from the urine within 24 h indicating that no delay between Part 1 and Part 2 of the test seems necessary. However, an adequate urine flow must be maintained throughout the test since a renal clearance/urine flow relationship exists, with fluorescein excretion being increased with increasing urine volume.

[The clinical value of an oral test of pancreatic function with fluorescein dilaurate (author's transl)]. / Zur klinischen Wertigkeit des oralen Pankreasfunktionstets mit Fluoreszein-Dilaurat.

Exocrine insufficiency of the pancreas was identified by decreased splitting of the ester substrate and thus diminished excretion of fluorescein in the urine of persons with normal pancreatic function (test excretion). Unesterified fluorescein served to ascertain the standard excretion of fluorescein (= 100%). The relation of test excretion to standard excretion was expressed in %. Values of less than 20% in collected urine are pathologic. The range of 20-30% is questionable. Normal persons showed 30% or more. The method described is simple and without problems for the patient. The test was accurate in 93% of patients with a false negative in 1%. Practicability and results recommend the test as a screening method.

Investigation on the fate of orally administered DEAE-dextran in rats.

The breakdown of the carbohydrates by the colonic bacterial flora can cause intestinal symptoms, such as meteorism, abdominal pain and diarrhoea. The ability of digestive enzymes and colonic bacterial flora to break down the DEAE-dextran, a new lipid lowering resin, was investigated in rats. DEAE-dextran appeared to be unaffected by either enzyme activity in the small intestine or bacterial flora in the large intestine. This may be important when dealing with the pharmacological activity of DEAE-dextran and estimating its side effects. Small intestinal transit rate appeared to be accelerated by oral DEAE-dextran in rats.

Serum PABA and fluorescein in the course of Bz-Ty-PABA and pancreolauryl test as an index of exocrine pancreatic insufficiency.

Forty-six subjects (20 chronic pancreatitis, 7 chronic liver disease, 7 recovered from acute pancreatitis, 2 Crohn's disease, and 10 healthy controls) classified by S-C test as having normal pancreatic function (26 subjects), or moderate (10 subjects) and severe (10 cases) pancreatic insufficiency, were given, on different days, 1 g of oral PABA or 348 mg of oral fluorescein dilaurate. At the 1st, 2nd, and 4th hours (PABA) and the 2nd, 4th, and 6th hours (fluorescein) serum samples were taken for assay. In the presence of severe exocrine pancreatic insufficiency, the sensitivity of the fluorescein serum levels was higher than that observed for the PABA (100% and 80%, respectively), and quite similar to that shown by the urinary tests (100% and 70%, respectively). On the contrary, in presence of moderate pancreatic insufficiency, both the urinary test (pancreolauryl and (PABA) give a sensitivity higher than that found in the serum tests (30-40% and 10-30%, respectively). The parallel combination of both the serum or urinary tests does not significantly improve the sensitivity of the single test. These results suggest that the serum PABA and serum fluorescein tests can be valid choice when a prolonged urinary collection is difficult, i.e., in children and in elderly patients. However, the slight diagnostic gain does not justify the routine use of both urinary and serum tests.

Route of absorption of drug and ointment after application to the eye.

Chloramphenicol, tetracycline hydrochloride, sodium sulfacetamide, and fluorescein sodium prepared in both aqueous solutions and ointments were placed in the conjunctival sac of humans. Each drug soon was tasted in the back of the mouth with no difference being noticed with the use of aqueous solution or ointment. Tetracycline and fluorescein studies showed that systemic absorption were similar regardless of whether solution or ointment were used. Furthermore, it was found that the ointment passed through the lacrimal drainage system and into the nose and throat. The ocular contact time of ointment with the eye is greater than that of water, and ointment is much more slowly absorbed via the lacrimal drainage system. Both the drugs and the ointment base applied topically to the eye travel through the nasolacrimal system as the way of elimination when given in the small volumes that are held by the conjunctival sac.

Fluorescein dilaurate--tubeless test for pancreatic exocrine failure.

The usefulness of fluorescein dilaurate as an indicator of pancreatic exocrine failure has been assessed in 70 patients and normal volunteers. The test consisted of a comparison of urinary fluorescein excretion after ingestion of fluorescein dilaurate with that after ingestion of unesterified fluorescein. The test was easy to perform and acceptable to the patients. The sensitivity of the test was 95%. There was a false-positive rate of 11% in a group of patients who had steatorrhoea which was non-pancreatic in origin. The test can be a useful screening test for the exclusion of pancreatic exocrine failure as a cause of steatorrhoea and can be conducted in outpatients.