Characterization of a Fibrin Glue-Gdnf Slow-Release Preparation

1998 ◽  
Vol 7 (1) ◽  
pp. 53-61
Author(s):  
Henrich Cheng ◽  
Matt Fraidakis ◽  
Birger Blombäck ◽  
Paul Lapchak ◽  
Barry Hoffer ◽  
...  

One novel method to deliver trophic factor locally in the CNS is to mix it into fibrin glue. In the present studies, [125I]-labeled GDNF-containing fibrin glue balls were used to determine binding and spread of the trophic factor. First, the binding of different concentrations of [125I]-labelèd GDNF in fibrin glue was determined in vitro. Within the six concentrations used (from 200 nM to 0.004 nM, 0 M as control), there was a strong linear correlation between the [125I]-GDNF concentration and the recovered radioactivity (r = 0.992). The mean bound radioactivity in 16 samples with 4 nM [125I]-GDNF was 71262 + 2710 CPM, and accounted for 89.8% of the mean initial count of free [125I]-GDNF (79369 + 3499 CPM). Second, [125I]-GDNF-containing glue balls were implanted into the anterior chamber of adult rats. The implanted fibrin glue balls decreased in size with time, but could still be identified on the irises 2 wk after implantation. Radioactivity was concentrated at the implantation sites in the early stages with a distribution in the surrounding iris tissue, which became separated into focal radioactive spots at the third week. Counts of radioactivity were significantly higher in the [125I]-GDNF glue ball-implanted irises than controls until 14 days after implantation. A study of the [125I] decay over time using least-squares linear regression demonstrated first-order kinetics (r = —0.98, p < 0.02) with k = 0.0091 and T 1/2 = 76 h. Finally, [125I]-GDNF–containing glue balls were implanted in the spinal cord of adult rats. Radioactivity was concentrated at the implantation sites in the early stages and was later distributed more widely in the surrounding thoracic cord. The [125I]-GDNF–containing glue degraded over time and became a porous meshwork with decreasing radioactivity at the later time points. Radioactivity in the spinal cords subjected to implantation of [125I]-GDNF–containing glue balls was higher than in controls for 14 days. Study of the [125I] decay by time with least-squares linear regression demonstrated first-order kinetics (r = -0.97, p = 0.001) with T 1/2 = 75.6 h. We conclude that the trophic factor GDNF becomes bound in the fibrin glue matrix from which it is gradually released. Our results suggest that fibrin glue is an effective substrate for keeping a trophic factor localized in situ for a finite period, protected from the circulation, surrounding aqueous humor or CSF.

1950 ◽  
Vol 33 (6) ◽  
pp. 703-722 ◽  
Author(s):  
C. W. Sheppard ◽  
W. R. Martin

The exchange of potassium between cells and plasma of heparinized human blood has been studied in vitro using the radioactive isotope K42. The changes in cell and plasma specific activity are characteristic of a simple two-compartment system. The mean of seven determinations of the exchange rate at 38°C. is 1.8 per cent of the cellular potassium per hour. The results indicate that at 38°C. the rate is relatively insensitive to oxygenation or reduction of the hemoglobin, and to 1200 r of gamma radiation. With varying temperature the rate follows pseudo first order kinetics with a Q10 of 2.35. Below 15°C. the rate of loss of potassium exceeds the rate of uptake.


Author(s):  
Andrew Gelman ◽  
Deborah Nolan

This chapter addresses the descriptive treatment of linear regression with a single predictor: straight-line fitting, interpretation of the regression line and standard deviation, the confusing phenomenon of “regression to the mean,” correlation, and conducting regressions on the computer. These concepts are illustrated with student discussions and activities. Many examples are of the sort commonly found in statistics textbooks, but the focus here is on how to work the examples into student-participation activities rather than simply examples to be read or shown on the blackboard. Topics include the following relationships: height and income, height and hand span, world population over time, and exam scores.


1980 ◽  
Vol 17 (04) ◽  
pp. 1087-1093 ◽  
Author(s):  
Richard C. Hertzberg ◽  
Vincent F. Gallucci

The general solution of a Markov model for first-order kinetics is developed as a sum of independent, multinomially distributed random processes. Fluctuations in the mean and variance functions are discussed and shown to be unrelated in time during the early phase of the reaction. Numerical examples are presented for two- and three-component systems.


1980 ◽  
Vol 17 (4) ◽  
pp. 1087-1093 ◽  
Author(s):  
Richard C. Hertzberg ◽  
Vincent F. Gallucci

The general solution of a Markov model for first-order kinetics is developed as a sum of independent, multinomially distributed random processes. Fluctuations in the mean and variance functions are discussed and shown to be unrelated in time during the early phase of the reaction. Numerical examples are presented for two- and three-component systems.


2019 ◽  
Vol 85 (2) ◽  
pp. 161-189 ◽  
Author(s):  
Matthew J Russell ◽  
Oliver E Jensen

Abstract Transport in biological systems often occurs in complex spatial environments involving random structures. Motivated by such applications, we investigate an idealized model for solute transport past an array of point sinks, randomly distributed along a line, which remove solute via first-order kinetics. Random sink locations give rise to long-range spatial correlations in the solute field and influence the mean concentration. We present a non-standard approach in evaluating these features based on rationally approximating integrals of a suitable Green’s function, which accommodates contributions varying on short and long lengthscales and has deterministic and stochastic components. We refine the results of classical two-scale methods for a periodic sink array (giving more accurate higher-order corrections with non-local contributions) and find explicit predictions for the fluctuations in concentration and disorder-induced corrections to the mean for both weakly and strongly disordered sink locations. Our predictions are validated across a large region of parameter space.


1990 ◽  
Vol 6 (1) ◽  
pp. 63-74 ◽  
Author(s):  
R.A.L. Carter ◽  
M.S. Srivastava ◽  
V.K. Srivastava ◽  
A. Ullah

We first present an unbiased estimator of the MSE matrix of the Stein-rule estimator of the coefficient vector in a normal linear regression model. The Steinrule estimator can be used with both its estimated MSE matrix and with the least-squares MSE matrix to form confidence ellipsoids. We derive the approximate expected squared volumes and coverage probabilities of these confidence sets and discuss their ranking. These results can be applied to the conditional prediction of the mean of the endogenous variable. We also consider the power of F-tests which employ the Stein-rule estimator in place of the least-squares estimator.


1986 ◽  
Vol 49 (11) ◽  
pp. 904-908 ◽  
Author(s):  
L. ABABOUCH ◽  
M.M. ALAOUI ◽  
F.F. BUSTA

Histamine levels were determined in 248 samples of fish commercially processed in Morocco. Concentrations ranging from &lt;0.01 to 694 mg/100 g of fish (mg%) were observed. The mean value was 12.33 mg% (sardines, 9.75; mackerel, 13.74; tuna 9.86) and the standard deviation was 55.28 mg% (sardines, 43.21; mackerel, 71.99; tuna, 25.05). The bulk of the samples (85.5%) had low histamine levels (&lt;10 mg%); 26 samples (10.5%) had levels within the range 10–50 mg% and should be classified as not from fresh fish or of low quality; 10 samples (4%) had toxicologically significant levels, above 50 mg%. Tuna fish was more susceptible to histamine development than were sardines or mackerel; 7% of tuna fish samples contained levels above 50 mg% as compared to 3.7% and 3.2% for sardines and mackerel, respectively. The percentage of samples containing levels above 50 mg% was somewhat higher for fish processed in the central region (7.1%) than the southern (4.3%) or northern (1.3%) regions; however, statistically the regional differences were not significantly different. Histamine development in sardines demonstrated first-order kinetics. Reaction rates ranged from 0.00200 to 0.000421 mn−1. Refrigeration controlled histamine development. Fish held at 8°C showed a shelf life 12 h longer than fish held at 17°C. A combination of salting and refrigeration was more effective. Fish held at 8°C and salted at a level of 5 or 8% showed a shelf life 35 h longer than fish held at 17°C with no salt.


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